SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Edvinsson Lars) "

Sökning: WFRF:(Edvinsson Lars)

  • Resultat 1-50 av 420
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Edvinsson, Jacob C.A., et al. (författare)
  • MERTK in the rat trigeminal system : a potential novel target for cluster headache?
  • 2024
  • Ingår i: Journal of Headache and Pain. - 1129-2369 .- 1129-2377. ; 25:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The trigeminal system is key to the pathophysiology of migraine and cluster headache, two primary headache disorders that share many features. Recently, MER proto-oncogene tyrosine kinase (MERTK), a cell surface receptor, was strongly associated with cluster headache through genetic studies. Further, the MERTK ligand galectin-3 has been found to be elevated in serum of migraine patients. In this study, MERTK and MERTK ligands were investigated in key tissue to better understand their potential implication in the pathophysiology of primary headache disorders. Immunohistochemistry was used to map MERTK and galectin-3 expression in rat trigeminal ganglia. RT-qPCR was used to assess MERTK gene expression in blood, and ELISA immunoassays were used for MERTK ligand quantification in serum from study participants with and without cluster headache. MERTK gene expression was elevated in blood samples from study participants with cluster headache compared to controls. In addition, MERTK ligand galectin-3 was found at increased concentration in the serum of study participants with cluster headache, whereas the levels of MERTK ligands growth arrest specific 6 and protein S unaffected. MERTK and galectin-3 were both expressed in rat trigeminal ganglia. Galectin-3 was primarily localized in smaller neurons and to a lesser extent in C-fibres, while MERTK was found in satellite glia cells and in the outer membrane of Schwann cells. Interestingly, a strong MERTK signal was found specifically in the region proximal to the nodes of Ranvier. The overexpression of MERTK and galectin-3 in tissue from study participants with cluster headache, as well as the presence of MERTK in rat peripheral satellite glia cells and Schwann cells in the trigeminal ganglia, further highlights MERTK signalling as an interesting potential future therapeutic target in primary headache. Graphical Abstract: (Figure presented.)
  •  
2.
  • Erlandsson, Lena, et al. (författare)
  • Preliminary evidence that blocking the uptake of placenta-derived preeclamptic extracellular vesicles protects the vascular endothelium and prevents vasoconstriction
  • 2023
  • Ingår i: Scientific Reports. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Preeclampsia (PE) is a pregnancy syndrome characterized by hypertension and organ damage manifesting after 20 gestational weeks. The etiology is of multifactorial origin, where placental stress causes increased levels of placenta-derived extracellular vesicles (STBEVs) in the maternal circulation, shown to cause inflammation, endothelial activation, vasoconstriction, and anti-angiogenic activity. General endothelial dysfunction is believed to be initiated by endothelial insult during pregnancy that alters vascular function resulting in increased arterial stiffness, cardiac dysfunction, and increased risk of cardiovascular disease later in life. We compared the effect of normal and PE derived STBEVs in vitro on vascular contractility of human subcutaneous arteries using wire myography. Cellular structures of exposed vessels were investigated by transmission electron microscopy. We explored strategies to pharmacologically block the effects of the STBEVs on human vessels. The PE STBEVs caused significantly stronger angiotensin II-mediated contractions and extended structural damage to human subcutaneous arteries compared to normal STBEVs. These negative effects could be reduced by blocking vesicle uptake by endothelial cells, using chlorpromazine or specific antibodies towards the LOX-1 receptor. The therapeutic potential of blocking vesicle uptake should be further explored, to reduce the permanent damage caused on the vasculature during PE pregnancy to prevent future cardiovascular risk.
  •  
3.
  • Maddahi, Aida, et al. (författare)
  • Progesterone distribution in the trigeminal system and its role to modulate sensory neurotransmission : influence of sex
  • 2023
  • Ingår i: Journal of Headache and Pain. - 1129-2369. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Women are disproportionately affected by migraine, representing up to 75% of all migraine cases. This discrepancy has been proposed to be influenced by differences in hormone levels between the sexes. One such hormone is progesterone. Calcitonin gene-related peptide (CGRP) system is an important factor in migraine pathophysiology and could be influenced by circulating hormones. The purpose of this study was to investigate the distribution of progesterone and its receptor (PR) in the trigeminovascular system, and to examine the role of progesterone to modulate sensory neurotransmission. Methods: Trigeminal ganglion (TG), hypothalamus, dura mater, and the basilar artery from male and female rats were carefully dissected. Expression of progesterone and PR proteins, and mRNA levels from TG and hypothalamus were analyzed by immunohistochemistry and real-time quantitative PCR. CGRP release from TG and dura mater were measured using an enzyme-linked immunosorbent assay. In addition, the vasomotor effect of progesterone on male and female basilar artery segments was investigated with myography. Results: Progesterone and progesterone receptor -A (PR-A) immunoreactivity were found in TG. Progesterone was located predominantly in cell membranes and in Aδ-fibers, and PR-A was found in neuronal cytoplasm and nucleus, and in satellite glial cells. The number of positive progesterone immunoreactive cells in the TG was higher in female compared to male rats. The PR mRNA was expressed in both hypothalamus and TG; however, the PR expression level was significantly higher in the hypothalamus. Progesterone did not induce a significant change neither in basal level nor upon stimulated release of CGRP from dura mater or TG in male or female rats when compared to the vehicle control. However, pre-treated with 10 µM progesterone weakly enhanced capsaicin induced CGRP release observed in the dura mater of male rats. Similarly, in male basilar arteries, progesterone significantly amplified the dilation in response to capsaicin. Conclusions: In conclusion, these results highlight the potential for progesterone to modulate sensory neurotransmission and vascular responses in a complex manner, with effects varying by sex, tissue type, and the nature of the stimulus. Further investigations are needed to elucidate the underlying mechanisms and physiological implications of these findings.
  •  
4.
  • Bömers, Jesper Peter, et al. (författare)
  • The MEK Inhibitor Trametinib Improves Outcomes following Subarachnoid Haemorrhage in Female Rats
  • 2022
  • Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 15:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Aneurysmal subarachnoid haemorrhage (SAH) is a haemorrhagic stroke that causes approximately 5% of all stroke incidents. We have been working on a treatment strategy that targets changes in cerebrovascular contractile receptors, by blocking the MEK/ERK1/2 signalling pathway. Recently, a positive effect of trametinib was found in male rats, but investigations of both sexes in pre-clinical studies are an important necessity. In the current study, a SAH was induced in female rats, by autologous blood-injection into the pre-chiasmatic cistern. This produces a dramatic, transient increase in intracranial pressure (ICP) and an acute and prolonged decrease in cerebral blood flow. Rats were then treated with either vehicle or three doses of 0.5 mg/kg trametinib (specific MEK/ERK1/2 inhibitor) intraperitoneally at 3, 9, and 24 h after the SAH. The outcome was assessed by a panel of tests, including intracranial pressure (ICP), sensorimotor tests, a neurological outcome score, and myography. We observed a significant difference in arterial contractility and a reduction in subacute increases in ICP when the rats were treated with trametinib. The sensory motor and neurological outcomes in trametinib-treated rats were significantly improved, suggesting that the improved outcome in females is similar to that of males treated with trametinib.
  •  
5.
  • Christiansen, Isabella Mai, et al. (författare)
  • Dual action of the cannabinoid receptor 1 ligand arachidonyl-2′-chloroethylamide on calcitonin gene-related peptide release
  • 2022
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 23
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Based on the current understanding of the role of neuropeptide signalling in migraine, we explored the therapeutic potential of a specific cannabinoid agonist. The aim of the present study was to examine the effect of the synthetic endocannabinoid (eCB) analogue, arachidonyl-2′-chloroethylamide (ACEA), on calcitonin gene-related peptide (CGRP) release in the dura and trigeminal ganglion (TG), as cannabinoids are known to activate Gi/o-coupled cannabinoid receptors type 1 (CB1), resulting in neuronal inhibition. Methods: The experiments were performed using the hemi-skull model and dissected TGs from male Sprague-Dawley rats. CGRP release was induced by either 60 mM K+ (for depolarization-induced stimulation) or 100 nM capsaicin (for transient receptor potential vanilloid 1 (TRPV1) -induced stimulation) and measured using an enzyme-linked immunosorbent assay. The analysis of CGRP release data was combined with immunohistochemistry in order to study the cellular localization of CB1, cannabinoid receptor type 2 (CB2), CGRP and receptor activity modifying protein 1 (RAMP1), a subunit of the functional CGRP receptor, in the TG. Results: CB1 was predominantly expressed in neuronal somas in which colocalization with CGRP was observed. Furthermore, CB1 exhibited colocalization with RAMP1 in neuronal Aδ-fibres but was not clearly expressed in the CGRP-immunoreactive C-fibres. CB2 was mainly expressed in satellite glial cells and did not show substantial colocalization with either CGRP or RAMP1. Without stimulation, 140 nM ACEA per se caused a significant increase in CGRP release in the dura but not TG, compared to vehicle. Furthermore, 140 nM ACEA did not significantly modify neither K+- nor capsaicin-induced CGRP release. However, when the TRPV1 blocker AMG9810 (1 mM) was coapplied with ACEA, K+-induced CGRP release was significantly attenuated in the TG and dura. Conclusions: Results from the present study indicate that ACEA per se does not exhibit antimigraine potential due to its dual agonistic properties, resulting in activation of both CB1 and TRPV1, and thereby inhibition and stimulation of CGRP release, respectively.
  •  
6.
  • Edvinsson, Jacob C.A., et al. (författare)
  • Neuropeptides and the Nodes of Ranvier in Cranial Headaches
  • 2022
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 12
  • Forskningsöversikt (refereegranskat)abstract
    • The trigeminovascular system (TGV) comprise of the trigeminal ganglion with neurons and satellite glial cells, with sensory unmyelinated C-fibers and myelinated Aδ-fibers picking up information from different parts of the head and sending signals to the brainstem and the central nervous system. In this review we discuss aspects of signaling at the distal parts of the sensory fibers, the extrasynaptic signaling between C-fibers and Aδ-fibers, and the contact between the trigeminal fibers at the nerve root entry zone where they transit into the CNS. We also address the possible role of the neuropeptides calcitonin gene-related peptide (CGRP), the neurokinin family and pituitary adenylyl cyclase-activating polypeptide 38 (PACAP-38), all found in the TGV system together with their respective receptors. Elucidation of the expression and localization of neuropeptides and their receptors in the TGV system may provide novel ways to understand their roles in migraine pathophysiology and suggest novel ways for treatment of migraine patients.
  •  
7.
  • Erdling, André, et al. (författare)
  • Changes in P2Y6 receptor-mediated vasoreactivity following focal and global ischemia
  • 2022
  • Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 10:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Ischemia, both in the form of focal thromboembolic stroke and following subarachnoid hemorrhage (SAH), causes upregulation of vasoconstrictive receptor systems within the cerebral vasculature. Descriptions regarding changes in purinergic signaling following ischemia are lacking, especially when the importance of purinergic signaling in regulating vascular tone is taken into consideration. This prompted us to evaluate changes in P2Y6-mediated vasomotor reactivity in two different stroke models in rat. We used wire myography to measure changes in cerebral vasoreactivity to the P2Y6 agonist UDP-β-S following either experimental SAH or transient middle cerebral artery occlusion. Changes in receptor localization or receptor expression were evaluated using immunohistochemistry and quantitative flow cytometry. Transient middle cerebral artery occlusion caused an increase in Emax when compared to sham (233.6 [206.1–258.5]% vs. 161.1 [147.1–242.6]%, p = 0.0365). No such change was seen following SAH. Both stroke models were associated with increased levels of P2Y6 receptor expression in the vascular smooth muscle cells (90.94 [86.99–99.15]% and 93.79 [89.96–96.39]% vs. 80.31 [70.80–80.86]%, p = 0.021) and p = 0.039 respectively. There was no change in receptor localization in either of the stroke models. Based on these findings, we conclude that focal ischemic stroke increases vascular sensitivity to UDP-β-S by upregulating P2Y6 receptors on vascular smooth muscle cells while experimental SAH did not induce changes in vasoreactivity in spite of increased P2Y6 receptor expression.
  •  
8.
  • Ingman, Gustav, 1989- (författare)
  • Essays on Stockholm’s real estate market 1730–2020
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This dissertation examines the long-run development of Stockholm’s real estate market between the years 1730 and 2020. Building on the city’s vast archival sources of housing transactions, it presents new insights into the historical price movements and the class and gender composition of the people that were engaged in the housing market.In five articles, three overarching themes are addressed. Firstly, Stockholm’s real estate price development between 1730 and 1875 is reconstructed. The new indices are then linked to existing ones so that prices can be followed into the present. Perhaps the most striking finding is that the last decades of rapidly rising prices had a precursor in the late 1800s market. Secondly, the new indices are used to assess the historical existence of turbulence and bubbles. While several severe price declines are detected, not least in periods of price increases and world wars, the buildup to the financial crisis of 1990 stands out as unique with its explosive price surge. Thirdly, archival material with information about historical real estate transactions is used to examine the class and gender composition of real estate market participants from 1730 to 1875. While the class composition remained stable, women’s participation was transformed as more unmarried women started to invest in housing towards the end of the investigated period. It highlights a tension between formal regulations and the praxis of women living in an increasingly commercialized city.This thesis puts Stockholm’s present real estate price boom in a historical perspective. It discusses earlier periods of booms and busts, and maps resemblances and differences with the present situation. Furthermore, it provides new empirical data that can be useful for future researchers.
  •  
9.
  • Mostajeran, Maryam, et al. (författare)
  • Repair-related molecular changes during recovery phase of ischemic stroke in female rats
  • 2022
  • Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Some degree of spontaneous recovery is usually observed after stroke. Experimental studies have provided information about molecular mechanisms underlying this recovery. However, the majority of pre-clinical stroke studies are performed in male rodents, and females are not well studied. This is a clear discrepancy when considering the clinical situation. Thus, it is important to include females in the evaluation of recovery mechanisms for future therapeutic strategies. This study aimed to evaluate spontaneous recovery and molecular mechanisms involved in the recovery phase two weeks after stroke in female rats. Methods: Transient middle cerebral artery occlusion was induced in female Wistar rats using a filament model. Neurological functions were assessed up to day 14 after stroke. Protein expression of interleukin 10 (IL-10), transforming growth factor (TGF)-β, neuronal specific nuclei protein (NeuN), nestin, tyrosine-protein kinase receptor Tie-2, extracellular signal-regulated kinase (ERK) 1/2, and Akt were evaluated in the peri-infarct and ischemic core compared to contralateral side of the brain at day 14 by western blot. Expression of TGF-β in middle cerebral arteries was evaluated by immunohistochemistry. Results: Spontaneous recovery after stroke was observed from day 2 to day 14 and was accompanied by a significantly higher expression of nestin, p-Akt, p-ERK1/2 and TGF-β in ischemic regions compared to contralateral side at day 14. In addition, a significantly higher expression of TGF-β was observed in occluded versus non-occluded middle cerebral arteries. The expression of Tie-2 and IL-10 did not differ between the ischemic and contralateral sides. Conclusion: Spontaneous recovery after ischemic stroke in female rats was coincided by a difference observed in the expression of molecular markers. The alteration of these markers might be of importance to address future therapeutic strategies.
  •  
10.
  • Reducha, Philip Victor, et al. (författare)
  • Could Experimental Inflammation Provide Better Understanding of Migraines?
  • 2022
  • Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:15
  • Forskningsöversikt (refereegranskat)abstract
    • Migraines constitute a common neurological and headache disorder affecting around 15% of the world’s population. In addition to other mechanisms, neurogenic neuroinflammation has been proposed to play a part in migraine chronification, which includes peripheral and central sensitization. There is therefore considerable evidence suggesting that inflammation in the intracranial meninges could be a key element in addition to calcitonin gene-related peptide (CGRP), leading to sensitization of trigeminal meningeal nociceptors in migraines. There are several studies that have utilized this approach, with a strong focus on using inflammatory animal models. Data from these studies show that the inflammatory process involves sensitization of trigeminovascular afferent nerve terminals. Further, by applying a wide range of different pharmacological interventions, insight has been gained on the pathways involved. Importantly, we discuss how animal models should be used with care and that it is important to evaluate outcomes in the light of migraine pathology.
  •  
11.
  • Rehnström, Mimmi, et al. (författare)
  • Ovariectomy Reduces Vasocontractile Responses of Rat Middle Cerebral Arteries After Focal Cerebral Ischemia
  • 2022
  • Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 79:1, s. 122-128
  • Tidskriftsartikel (refereegranskat)abstract
    • ABSTRACT: Effects of sex hormones on stroke outcome are not fully understood. A deleterious consequence of cerebral ischemia is upregulation of vasoconstrictor receptors in cerebral arteries that exacerbate stroke injury. Here, we tested the hypothesis that female sex hormones alter vasocontractile responses after experimental stroke in vivo or after organ culture in vitro, a model of vasocontractile receptor upregulation. Female rats with intact ovaries and ovariectomized (OVX) females treated with 17β-estradiol, progesterone, or placebo were subjected to transient, unilateral middle cerebral artery occlusion followed by reperfusion (I/R). The maximum contractile response, measured my wire myography, in response to the endothelin B receptor agonist sarafotoxin 6c was increased in female arteries after I/R, but the maximum response was significantly lower in arteries from OVX females. Maximum contraction mediated by the serotonin agonist 5-carboxamidotryptamine was diminished after I/R, with arteries from OVX females showing a greater decrease in maximum contractile response. Contraction elicited by angiotensin II was similar in all arteries. Neither estrogen nor progesterone treatment of OVX females affected I/R-induced changes in endothelin B- and 5-carboxamidotryptamine-induced vasocontraction. These findings suggest that sex hormones do not directly influence vasocontractile alterations that occur after ischemic stroke; however, loss of ovarian function does impact this process.
  •  
12.
  • Thyr, Jakob, 1979-, et al. (författare)
  • Energy Alignment of Quantum-Confined ZnO Particles with Copper Oxides for Heterojunctions with Improved Photocatalytic Performance
  • 2022
  • Ingår i: ACS Nanoscience Au. - : American Chemical Society (ACS). - 2694-2496. ; 2:2, s. 128-139
  • Tidskriftsartikel (refereegranskat)abstract
    • The ability to control electronic states by utilizing quantum confinement of one of the material components in heterojunctions is a promising approach to perform energy-level matching. In this work, we report the possibility to achieve optimum energy alignment in heterojunctions made from size-controlled quantum dots (Q-dots) of ZnO in combination with three copper oxides: Cu2O, Cu4O3, and CuO. Quantum confinement effects on the ZnO nanoparticles in the diameter range 2.6–7.4 nm showed that the direct optical band gap decreased from 3.99 to 3.41 eV, with a dominating shift occurring in the conduction band (CB) edge, and thus the possibility to obtain close to 0.6 eV CB edge shift by controlling the size of ZnO. The effect was utilized to align the electronic bands in the ZnO Q-dot/copper oxide heterojunctions to allow for charge transfer between the materials and to test the ability to improve the photocatalytic performance for the system, evaluated by the transformation of a dye molecule in water. The catalyst materials were investigated by X-ray diffraction, scanning electron microscopy, ultraviolet–visible (UV–vis), photoluminescence, and Raman spectroscopy. The most promising material combination was found to be the Cu2O copper oxide in combination with an energy aligned ZnO Q-dot system with approximately 7 nm diameter, showing strong synergy effects in good agreement with the energy-level analysis, outperforming the added effect of its individual components, ZnO-Q-dots and Cu2O, by about 140%. The results show that utilization of a heterojunction with controllable energy alignment can provide a drastically improved photocatalytic performance. Apart from increased photocatalytic activity, specific surface states of ZnO are quenched when the heterojunction is created. It is anticipated that the same approach can be utilized in several material combinations with the added benefit of a system with controllable overpotential and thus added specificity for the targeted reduction reaction.
  •  
13.
  • Bayrak Pehlivan, Ilknur, et al. (författare)
  • Electrochromic solar water splitting using a cathodic WO3 electrocatalyst
  • 2021
  • Ingår i: Nano Energy. - : Elsevier. - 2211-2855 .- 2211-3282. ; 81
  • Tidskriftsartikel (refereegranskat)abstract
    • Solar-driven water splitting is an emerging technology with high potential to generate fuel cleanly and sustainably. In this work, we show that WO3 can be used as a cathodic electrocatalyst in combination with (Ag,Cu) InGaSe2 solar cell modules to produce hydrogen and provide electrochromic functionality to water splitting devices. This electrochromic effect can be used to monitor the charge state or performance of the catalyst for process control or for controlling the temperature and absorbed heat due to tunable optical modulation of the electrocatalyst. WO3 films coated on Ni foam, using a wide range of different sputtering conditions, were investigated as cathodic electrocatalysts for the water splitting reaction. The solar-to-hydrogen (STH) efficiency of solar-driven water electrolysis was extracted using (Ag,Cu)InGaSe2 solar cell modules with a cell band gap varied in between 1.15 and 1.25 eV with WO3 on Ni foam-based electrolyzers and yielded up to 13% STH efficiency. Electrochromic properties during water electrolysis were characterized for the WO3 films on transparent substrate (indium tin oxide). Transmittance varied between 10% and 78% and the coloration efficiency at a wavelength of 528 nm and the overpotential of 400 mV was 40 cm(2) C-1. Hydrogen ion consumption in ion intercalation for electrochromic and hydrogen gas production for water electrolysis processes was discussed.
  •  
14.
  • Bayrak Pehlivan, Ilknur, et al. (författare)
  • NiMoV and NiO-based catalysts for efficient solar-driven water splitting using thermally integrated photovoltaics in a scalable approach
  • 2021
  • Ingår i: iScience. - : Cell Press. - 2589-0042. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, a trimetallic NiMoV catalyst is developed for the hydrogen evolution reaction and characterized with respect to structure, valence, and elemental distribution. The overpotential to drive a 10 mA cm−2 current density is lowered from 94 to 78 mV versus reversible hydrogen electrode by introducing V into NiMo. A scalable stand-alone system for solar-driven water splitting was examined for a laboratory-scale device with 1.6 cm2 photovoltaic (PV) module area to an up-scaled device with 100 cm2 area. The NiMoV cathodic catalyst is combined with a NiO anode in alkaline electrolyzer unit thermally connected to synthesized (Ag,Cu) (In,Ga)Se2 ((A)CIGS) PV modules. Performance of 3- and 4-cell interconnected PV modules, electrolyzer, and hydrogen production of the PV electrolyzer are examined between 25°C and 50°C. The PV-electrolysis device having a 4-cell (A)CIGS under 100 mW cm−2 illumination and NiMoV-NiO electrolyzer shows 9.1% maximum and 8.5% averaged efficiency for 100 h operation.
  •  
15.
  • Bömers, Jesper Peter, et al. (författare)
  • Pre-chiasmatic, single injection of autologous blood to induce experimental subarachnoid hemorrhage in a rat model
  • 2021
  • Ingår i: Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; 2021:172
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite advances in treatment over the last decades, subarachnoid hemorrhage (SAH) continues to carry a high burden of morbidity and mortality, largely afflicting a fairly young population. Several animal models of SAH have been developed to investigate the pathophysiological mechanisms behind SAH and to test pharmacological interventions. The pre-chiasmatic, single injection model in the rat presented in this article is an experimental model of SAH with a predetermined blood volume. Briefly, the animal is anesthetized, intubated, and kept under mechanical ventilation. Temperature is regulated with a heating pad. A catheter is placed in the tail artery, enabling continuous blood pressure measurement as well as blood sampling. The atlantooccipital membrane is incised and a catheter for pressure recording is placed in the cisterna magna to enable intracerebral pressure measurement. This catheter can also be used for intrathecal therapeutic interventions. The rat is placed in a stereotaxic frame, a burr hole is drilled anteriorly to the bregma, and a catheter is inserted through the burr hole and placed just anterior to the optic chiasm. Autologous blood (0.3 mL) is withdrawn from the tail catheter and manually injected. This results in a rise of intracerebral pressure and a decrease of cerebral blood flow. The animal is kept sedated for 30 min and given subcutaneous saline and analgesics. The animal is extubated and returned to its cage. The pre-chiasmatic model has a high reproducibility rate and limited variation between animals due to the pre-determined blood volume. It mimics SAH in humans making it a relevant model for SAH research.
  •  
16.
  • Calnan, Sonya, et al. (författare)
  • Development of Various Photovoltaic‐Driven Water Electrolysis Technologies for Green Solar Hydrogen Generation
  • 2021
  • Ingår i: Solar RRL. - : John Wiley & Sons. - 2367-198X. ; 6:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Direct solar hydrogen generation via a combination of photovoltaics (PV) and water electrolysis can potentially ensure a sustainable energy supply while minimizing greenhouse emissions. The PECSYS project aims at demonstrating asolar-driven electrochemical hydrogen generation system with an area >10 m2 with high efficiency and at reasonable cost. Thermally integrated PV electrolyzers(ECs) using thin-film silicon, undoped, and silver-doped Cu(In,Ga)Se2 and silicon heterojunction PV combined with alkaline electrolysis to form one unit are developed on a prototype level with solar collection areas in the range from 64 to2600 cm2 with the solar-to-hydrogen (StH) efficiency ranging from 4 to 13%. Electrical direct coupling of PV modules to a proton exchange membrane EC test the effects of bifacially (730 cm2 solar collection area) and to study the long-term operation under outdoor conditions (10 m2 collection area) is also investigated. In both cases, StH efficiencies exceeding 10% can be maintained over the test periods used. All the StH efficiencies reported are based on measured gas outflow using mass flow meters.
  •  
17.
  • Cao, Lei, et al. (författare)
  • Secondhand cigarette smoke induces increased expression of contractile endothelin receptors in rat coronary arteries via a MEK1/2 sensitive mechanism
  • 2021
  • Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 55:1, s. 50-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Cigarette smoke, a strong risk factor for cardiovascular diseases, upregulates contractile endothelin (ET) receptors in coronary arteries. The present study examined the effects of second hand cigarette smoke exposure on the contractile endothelin receptors and the role of the MEK1/2 pathway in rat coronary arteries. Design: Rats were exposed to secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of a MEK1/2 inhibitor, U0126 daily for another 4 weeks. Contractile responses of isolated coronary arteries were recorded by a sensitive wire myograph. The receptor protein expression levels were examined by Western blotting. Results: The results showed that SHS in vivo caused increased expression of ET receptors ETA and ETB, and that the MEK1/2 blocker U0126 significantly reversed SHS exposure-increased ETA-mediated contractile responses and protein levels. Similar alterations were observed in ETB receptors. U0126 showed dose-dependent effects on SHS-induced response on contractile property and protein levels of the ETB receptor. However, only the higher dose U0126 (15 mg/kg) had inhibitory effects on the ETA receptor. Conclusions: Taken together, our data show that SHS increases contractile ET receptors and MEK1/2 pathway inhibitor offsets SHS exposure-induced ETA and ETB receptor upregulation in rat coronary arteries.
  •  
18.
  • Edvinsson, Jacob C.A., et al. (författare)
  • Neurokinins and their receptors in the rat trigeminal system : Differential localization and release with implications for migraine pain
  • 2021
  • Ingår i: Molecular Pain. - : SAGE Publications. - 1744-8069. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Substance P (SP) and calcitonin gene-related peptide (CGRP) have both been considered potential drug candidates in migraine therapy. In recent years, CGRP receptor inhibition has been established as an effective treatment, in particular as a prophylactic for chronic migraine. Curiously, inhibition of neurokinin receptor 1 (NK1R) failed to alleviate acute migraine attacks in clinical trials, and the neurokinins were consequently abandoned as potential antimigraine candidates. The reason behind this has remained enigmatic. Utilizing immunohistochemistry and semi-quantitative cell counts the expression of neurokinins and their associated receptors was examined in the rat trigeminal ganglion. Immunohistochemistry results revealed SP co-localization in CGRP positive neurons and C-fibres, where it mainly concentrated at boutons. Neurokinin A (NKA) was observed in a population of C-fibres and small neurons where it could co-localize with SP. In contrast, neurokinin B (NKB) did not co-localize with SP and was observed in large/medium sized neurons and Aδ-fibres. All neurokinin receptors (NK1-3R) were found to be expressed in a majority of trigeminal ganglion neurons and A-fibres. The functional release of SP and CGRP in the trigeminovascular system was stimulated with either 60 mM K+ or 100 nM capsaicin and measured with an enzyme-linked immunosorbent assay (ELISA). ELISA results established that SP can be released locally from trigeminovascular system. The released SP was comparatively minor compared to the CGRP release from stimulated dura mater, trigeminal ganglion neurons and fibres. We hypothesize that SP and CGRP signalling pathways may work in tandem to exacerbate painful stimuli in the TGV system.
  •  
19.
  • Edvinsson, Lars, et al. (författare)
  • Identifying New Antimigraine Targets : Lessons from Molecular Biology
  • 2021
  • Ingår i: Trends in Pharmacological Sciences. - : Elsevier BV. - 0165-6147. ; 42:4, s. 217-225
  • Forskningsöversikt (refereegranskat)abstract
    • Primary headaches are one of the most common conditions; migraine being most prevalent. Recent work on the pathophysiology of migraine suggests a mismatch in the communication or tuning of the trigeminovascular system, leading to sensitization and the release of calcitonin gene-related peptide (CGRP). In the current Opinion, we use the up-to-date molecular understanding of mechanisms behind migraine pain, to provide novel aspects on how to modify the system and for the development of future treatments; acute as well as prophylactic. We explore the distribution and the expression of neuropeptides themselves, as well as certain ion channels, and most importantly how they may act in concert as modulators of excitability of both the trigeminal C neurons and the Aδ neurons.
  •  
20.
  •  
21.
  • Hansson, Emma, 1981, et al. (författare)
  • First‐year complications after immediate breast reconstruction with a biological and a synthetic mesh in the same patient: A randomized controlled study
  • 2021
  • Ingår i: World Journal of Surgical Oncology. - : Wiley. - 1477-7819 .- 0022-4790 .- 1096-9098. ; 123:1, s. 80-88
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Even though meshes and matrices are widely used in breast reconstruction, there is little high‐quality scientific evidence for their risks and benefits. The aim of this study was to compare first‐year surgical complication rates in implant‐based immediate breast reconstruction with a biological mesh with that of a synthetic mesh, in the same patient. Methods This study is a clinical, randomized, prospective trial. Patients operated on with bilateral mastectomy and immediate breast reconstruction were randomized to biological mesh on one side and synthetic mesh on the other side. Results A total of 48 breasts were randomized. As the synthetically and the biologically reconstructed breasts that were compared belonged to the same woman, systemic factors were exactly the same in the two groups. The most common complication was seroma formation with a frequency of 38% in the biological group and 3.8% in the synthetical group (p=.011). A higher frequency of total implant loss could be seen in the biologic mesh group (8.5% vs. 2%), albeit not statistically significant (p=.083). Conclusions In the same patient, a synthetic mesh seems to yield a lower risk for serious complications, such as implant loss, than a biological mesh.
  •  
22.
  • Krause, Diana N., et al. (författare)
  • Hormonal influences in migraine — interactions of oestrogen, oxytocin and CGRP
  • 2021
  • Ingår i: Nature Reviews Neurology. - : Springer Science and Business Media LLC. - 1759-4758 .- 1759-4766. ; 17:10, s. 621-633
  • Forskningsöversikt (refereegranskat)abstract
    • Migraine is ranked as the second highest cause of disability worldwide and the first among women aged 15–49 years. Overall, the incidence of migraine is threefold higher among women than men, though the frequency and severity of attacks varies during puberty, the menstrual cycle, pregnancy, the postpartum period and menopause. Reproductive hormones are clearly a key influence in the susceptibility of women to migraine. A fall in plasma oestrogen levels can trigger attacks of migraine without aura, whereas higher oestrogen levels seem to be protective. The basis of these effects is unknown. In this Review, we discuss what is known about sex hormones and their receptors in migraine-related areas in the CNS and the peripheral trigeminovascular pathway. We consider the actions of oestrogen via its multiple receptor subtypes and the involvement of oxytocin, which has been shown to prevent migraine attacks. We also discuss possible interactions of these hormones with the calcitonin gene-related peptide (CGRP) system in light of the success of anti-CGRP treatments. We propose a simple model to explain the hormone withdrawal trigger in menstrual migraine, which could provide a foundation for improved management and therapy for hormone-related migraine in women.
  •  
23.
  • Langhammer, David Michael, 1991- (författare)
  • Capturing Air Pollutants : Photochemical Adsorption and Degradation of SO2, NO2 and CO2 on Titanium Dioxide
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Titanium dioxide (TiO2) is a material with many useful properties. It is used most widely as a pigment in white paint, although in technological research it is better known for its ability to catalyze chemical reactions during light absorption. This process is referred to as photocatalysis, where the energy of the light is used to power the chemical reactions. This has enabled several interesting applications of TiO2, where it can for instance be applied to windows or façade walls to make their surfaces self-cleaning. Another implementation that has received much attention lately is artificial photosynthesis, where the light energy is used to transform CO2 and H2O into synthetic fuels. This thesis work contributes to the development of both these applications, although the main ambition is to show how three of the most common ambient air pollutant molecules, SO2, NO2 and CO2, can be captured at the surface of TiO2 by means of photocatalysis. Specifically, infrared (IR) spectroscopy and density functional theory (DFT) has been used as complementary tools of analysis to study the photocatalytic reactions that enable transformation of SO2, NO2 and CO2 into strongly bound sulfates, nitrates and carbonates, respectively. This combined experimental and theoretical approach has enabled a detailed description of how these reactions proceed and has further shown how the fundamental reactivity of the TiO2 surface changes upon light absorption.The work presented herein contributes to an increased understanding of photocatalysis and shows, quite generally, how molecules can be effectively captured at the surface of metal oxides by forming surface-integrated ionic adsorbates.
  •  
24.
  • Spray, Stine, et al. (författare)
  • Subacute phase of subarachnoid haemorrhage in female rats : Increased intracranial pressure, vascular changes and impaired sensorimotor function
  • 2021
  • Ingår i: Microvascular Research. - : Elsevier BV. - 0026-2862. ; 135
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Early brain injury (EBI) and delayed cerebral ischemia (DCI) after subarachnoid haemorrhage (SAH) has devastating consequences but therapeutic options and the underlying pathogenesis remain poorly understood despite extensive preclinical and clinical research. One of the drawbacks of most preclinical studies to date is that the mechanisms behind DCI after SAH are studied only in male animals. In this study we therefore established a female rat model of SAH in order to determine subacute pathophysiological changes that may contribute to DCI in females. Methods: Experimental SAH was induced in female rats by intracisternal injection of 300 μL of autologous blood. Sham operation served as a control. Neurological deficits and intracranial pressure measurements were evaluated at both 1 and 2 days after surgery. Additionally, changes in cerebral vascular contractility were evaluated 2 days after surgery using wire myography. Results: SAH in female rats resulted in sensorimotor deficits and decreased general wellbeing on both day 1 and day 2 after SAH. Intracranial pressure uniformly increased in all rats subjected to SAH on day 1. On day 2 the intracranial pressure had increased further, decreased slightly or remained at the level seen on day 1. Furthermore, female rats subjected to SAH developed cortical brain edema. Cerebral arteries, isolated 2 days after SAH, exhibited increased vascular contractions to endothelin-1 and 5-carboxamidotryptamine. Conclusion: In the subacute phase after SAH in female rats, we observed increased intracranial pressure, decreased wellbeing, sensorimotor deficits, increased vascular contractility and cortical brain edema. Collectively, these pathophysiological changes may contribute to DCI after SAH in females. Previous studies reported similar pathophysiological changes for male rats in the subacute phase after SAH. Thus, prevention of these gender-independent mechanisms may provide the basis for a universal treatment strategy for DCI after SAH. Nevertheless, preclinical studies of potential therapies should employ both male and female SAH models.
  •  
25.
  • Thyr, Jakob, 1979-, et al. (författare)
  • Polarized and non-polarized Raman spectroscopy of ZnO crystals : Method for determination of crystal growth and crystal plane orientation for nanomaterials
  • 2021
  • Ingår i: Journal of Raman Spectroscopy. - : John Wiley & Sons. - 0377-0486 .- 1097-4555. ; 52:8, s. 1395-1405
  • Tidskriftsartikel (refereegranskat)abstract
    • Analysis and determination of crystal orientation and exposed surface facets remain a challenge in nanomaterial science. In this work we show that polarized and non-polarized Raman spectroscopy can be useful tools to determine crystal plane orientation and conveniently be applied to spatial dimensions limited only by the diffraction limit of the excitation laser. The methodology is exemplified for wurtzite structured ZnO. Three different crystal facets, (0001), (1-100), and (11-20) of ZnO are investigated with angle resolved polarized Raman spectroscopy. The polarization direction dependences of the main Raman peaks are characterized and related to the experimental vibrational modes in the crystal lattice and corroborated by density functional theory (DFT) calculations using two different hybrid functionals. By exploiting the symmetry of the modes and differences in Raman intensity of the optically activated phonons, a simple model is derived for determining the relation between the polar and non-polar crystal orientation. The results are generalized to allow peak intensity ratio analysis using Raman spectroscopy with a non-polarized light source, making it compatible with Raman mapping, as well as to include a critical discussion on the ability to determine the crystal plane orientation and exposed crystal facets using this model for nano dimensional ZnO and equivalent models for other nanomaterials. As the approach allows for use of non-polarized light sources, near-field excitations and local plasmons can in an extension be utilized for determination of crystal orientation and exposed planes in dimensions much smaller than the diffraction limit.
  •  
26.
  • Belin, Andrea Carmine, et al. (författare)
  • Calcitonin gene-related peptide (CGRP) and cluster headache
  • 2020
  • Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 10:1
  • Forskningsöversikt (refereegranskat)abstract
    • Cluster headache (CH) is a severe primary headache with a prevalence of 1/1000 individuals, and a predominance in men. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, originating in trigeminal neurons and has a central role in CH pathophysiology. CGRP and the CGRP receptor complex have recently taken center stage as therapeutic targets for primary headaches, such as migraine. Multiple CGRP and CGRP receptor monoclonal antibodies, as well as small molecule antagonists (gepants) are on their way constituting a new frontier of migraine and possibly CH medication. During a CH attack, there is an activation of the trigeminal-autonomic reflex with the release of CGRP, and inversely if CGRP is administered to a CH patient in an active disease phase, it triggers an attack. Increased levels of CGRP have been found in ipsilateral jugular vein blood during the active phase of CH. This process is hypothesized to have a key role in the intense pain perception and in the associated distinctive vasodilation. So far, clinical tests of CGRP antibodies have been inconclusive in CH patients. This review summarizes the current state of knowledge on the role of CGRP in CH pathology, and as a target for future treatments.
  •  
27.
  • Edvinsson, Jacob Carl Alexander, et al. (författare)
  • Differences in pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide release in the trigeminovascular system
  • 2020
  • Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 40:12, s. 1296-1309
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Objective: The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides. Methods: In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K+ or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of PACAP and calcitonin gene-related peptide receptors and ligands. Results: Calcitonin gene-related peptide (CGRP) is released from the trigeminal ganglion and dura mater. In contrast, PACAP is only released from the trigeminal ganglion. We observed a weak correlation between the stimulated release of the two neuropeptides. PACAP-38 immunoreactivity was expressed alone and in a subpopulation of neurons in the trigeminal ganglion that also store calcitonin gene-related peptide. The receptor subtype PAC1 was mainly expressed in the satellite glial cells (SGCs), which envelop the neurons in the trigeminal ganglion, in some neuronal processes, inside the Aδ-fibres and in the outermost layer of the myelin sheath that envelopes the Aδ-fibres. Conclusion: Unlike CGRP, PACAP is only released within the trigeminal ganglion. This raises the question of whether a migraine therapy aimed at preventing peripheral PACAP signalling would be as successful as the CGRP signalling targeted treatments.
  •  
28.
  • Frederiksen, Simona D., et al. (författare)
  • Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case-Control and Case-Crossover Settings : A Systematic Review and Meta-Analysis
  • 2020
  • Ingår i: Headache. - : Wiley. - 0017-8748. ; 60:6, s. 1132-1164
  • Forskningsöversikt (refereegranskat)abstract
    • Objective: The aim of this systematic review and meta-analysis (SR-MA) was to identify signaling molecule profiles and blood-derived biomarkers in migraine and cluster headache (CH) patients. Background: Currently no migraine and CH valid biomarkers are available. Blood tests based on biomarker profiles have been used to gather information about the nervous system. Such tests have not yet been established within the primary headache field. Methods: Case-control and case-crossover studies investigating whole blood, plasma, and serum were identified worldwide. The qualitative synthesis focused on 9 signaling molecules (serotonin [5-HT], calcitonin gene-related peptide [CGRP], endothelin-1 [ET-1], neurokinin A, neurokinin B, neuropeptide Y, pituitary adenylate cyclase-activating peptide 38 [PACAP-38], substance P (SP), and vasoactive intestinal peptide) and the quantitative synthesis on 5-HT and CGRP (≥5 comparisons available). The meta-analysis was conducted using standard and 3-level random effect models. Results: Fifty-four eligible studies were identified (87.0% migraine, 9.3% CH, 3.7% migraine, and CH), and 2768 headache patients and 1165 controls included. Comparable fluctuations of 5-HT, CGRP, ET-1, PACAP-38, and SP in blood were generally observed between migraine and CH. Significant findings were observed for some subgroups and strata, for example, higher interictal and ictal 5-HT venous blood levels (ratio of means = 1.32, 95% CI: 1.08; 1.61; ratio of means = 1.23, 95% CI: 1.01; 1.49) in episodic migraine with aura with a female-dominated case group, higher interictal CGRP blood levels in episodic migraine (ratio of means = 1.63, 95% CI: 1.18; 2.26), and chronic migraine (ratio of means = 1.89, 95% CI: 1.33; 2.68), and higher ictal CGRP blood levels (ratio of means = 1.35, 95% CI: 1.09; 1.68) in episodic migraine were observed. In most subgroups, the quantitative synthesis revealed a high degree of heterogeneity between studies in part explained by the blood sampling site, specimen source, blood specimen, and sex distribution. Other potential confounders were age, aura, study quality, menstrual cycle, and methodology (eg, storage temperature). Conclusions: Potential migraine and CH signaling molecule profiles and biomarkers were revealed. Nevertheless, the high degree of heterogeneity between studies impedes identification of valid biomarkers but allowed us to assess the presence of confounders. Consideration of the potential confounders identified in this SR-MA might be of importance in the experimental planning of future studies. This consideration could be incorporated through establishment of specific guidelines.
  •  
29.
  • Golbidi, Saeid, et al. (författare)
  • Smoking and endothelial dysfunction
  • 2020
  • Ingår i: Current Vascular Pharmacology. - 1570-1611. ; 18:1, s. 1-11
  • Forskningsöversikt (refereegranskat)abstract
    • Cigarette smoking is one of the most important health concerns worldwide. Even though the rate of smoking is declining in developed countries, it is still experiencing growth in developing regions. Many studies have examined the relationship between smoking, as an established risk factor, and cardiovascular diseases. We provide an updated review of the underlying mechanisms of smokinginduced cardiovascular diseases, with a focus on the relationship between smoking and oxidative stress, particularly from the perspective of endothelial cell dysfunction. We review smoking-induced oxidative stress as a trigger for a generalized vascular inflammation associated with cytokine release, adhesion of inflammatory cells and, ultimately, disruption of endothelial integrity as a protective barrier layer. We also briefly discuss the harms related to the vaping of electronic cigarettes, which many erroneously consider as a safe alternative to smoking. We conclude that even though e-cigarette could be a helpful device during the transition period of cigarette quitting, it is by no means a safe substitute.
  •  
30.
  •  
31.
  • Le, Thi Lisa, et al. (författare)
  • CGRP in rat mesenteric artery and vein - receptor expression, CGRP presence and potential roles
  • 2020
  • Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999. ; 875
  • Tidskriftsartikel (refereegranskat)abstract
    • CGRP is a potent dilator of arteries and despite rich perivascular CGRP immunoreactivity in both arteries and veins the role of CGRP in veins remains unknown. The aim of the current study was to compare perivascular CGRP immunoreactivity and expression of CGRP receptor mRNA and CGRP receptor immunoreactivity in rat mesenteric arteries and veins. Furthermore, potential vasomotor effects of CGRP were explored in veins. Immunohistochemical studies reproduced rich perivascular CGRP innervation in arteries and in veins. Further, the presence of mRNA encoding the CGRP receptor subunits, CLR and RAMP1, were demonstrated in both arteries and veins using qPCR. Before comparing the vasoactive effects of CGRP in arteries and veins, we aimed to identify an experimental setting where vasomotor responses could be detected. Therefore, a length-tension study was performed in artery and vein segments. Whereas the arteries showed the characteristic monophasic curve with an IC/IC100 value of 0.9, surprisingly the veins showed a biphasic response with two corresponding IC/IC100 values of 0.7 and 0.9, respectively. There was no significant difference between fresh and cultured vasculature segments. To investigate whether a potential tension-dependent CGRP-induced dilation of veins caused the decline between the two IC/IC100 peaks, a second study was performed, with the CGRP receptor antagonist, BIBN4096BS (olcegepant) and the sensory nerve secretagogue, capsaicin. No significant vascular role of endogenous perivascular CGRP in mesenteric veins could be concluded, and a potential role of the rich perivascular CGRP and CGRP receptor abundancy in veins remains unknown.
  •  
32.
  • Rehnström, Mimmi, et al. (författare)
  • Transcriptome profiling revealed early vascular smooth muscle cell gene activation following focal ischemic stroke in female rats – comparisons with males
  • 2020
  • Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Women account for 60% of all stroke deaths and are more often permanently disabled than men, despite their higher observed stroke incidence. Considering the clinical population affected by stroke, an obvious drawback is that many pre-clinical and clinical studies only investigate young males. To improve therapeutic translation from bench to bedside, we believe that it is advantageous to include both sexes in experimental models of stroke. The aims of this study were to identify early cerebral vascular responses to ischemic stroke in females, compare the differential gene expression patterns with those seen in males, and identify potential new therapeutic targets. Results: Transient middle cerebral artery occlusion (tMCAO) was used to induce stroke in both female and male rats, the middle cerebral arteries (MCAs) were isolated 3 h post reperfusion and RNA was extracted. Affymetrix whole transcriptome expression profiling was performed on female (n = 12) MCAs to reveal differentially expressed genes. In total, 1076 genes had an increased expression and 879 genes a decreased expression in the occluded MCAs as compared with the control MCAs from female rats. An enrichment of genes related to apoptosis, regulation of transcription, protein autophosphorylation, inflammation, oxidative stress, and tissue repair and recovery were seen in the occluded MCA. The high expression genes chosen for qPCR verification (Adamts4, Olr1, JunB, Fosl1, Serpine1, S1pr3, Ccl2 and Socs3) were all shown to be upregulated in the same manner in both females and males after tMCAO (p < 0.05; n = 23). When comparing the differentially expressed genes in female MCAs (occluded and non-occluded) with our previous findings in males after tMCAO, a total of 297 genes overlapped (all groups had 32 genes in common). Conclusions: The cascades of processes initiated in the vasculature following reperfusion are complex. Dynamic gene expression alterations were observed in the occluded MCAs, and to a less pronounced degree in the non-occluded MCAs. Dysregulation of inflammation and blood-brain barrier breakdown are possible pharmacological targets. The sample of genes (< 1% of the differentially expressed genes) validated for this microarray did not reveal any sex differences. However, sex differences might be observed for other gene targets.
  •  
33.
  •  
34.
  • Sohn, Iben, et al. (författare)
  • The effects of CGRP in vascular tissue - Classical vasodilation, shadowed effects and systemic dilemmas
  • 2020
  • Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999. ; 881
  • Forskningsöversikt (refereegranskat)abstract
    • Vascular tissue consists of endothelial cells, vasoactive smooth muscle cells and perivascular nerves. The perivascular sensory neuropeptide CGRP has demonstrated potent vasodilatory effects in any arterial vasculature examined so far, and a local protective CGRP-circuit of sensory nerve terminal CGRP release and smooth muscle cell CGRP action is evident. The significant vasodilatory effect has shadowed multiple other effects of CGRP in the vascular tissue and we therefore thoroughly review vascular actions of CGRP on endothelial cells, vascular smooth muscle cells and perivascular nerve terminals. The actions beyond vasodilation includes neuronal re-uptake and neuromodulation, angiogenic, proliferative and antiproliferative, pro- and anti-inflammatory actions which vary depending on the target cell and anatomical location. In addition to the classical perivascular nerve-smooth muscle CGRP circuit, we review existing evidence for a shadowed endothelial autocrine pathway for CGRP. Finally, we discuss the impact of local and systemic actions of CGRP in vascular regulation and protection from hypertensive and ischemic heart conditions with special focus on therapeutic CGRP agonists and antagonists.
  •  
35.
  • Warfvinge, Karin, et al. (författare)
  • Cellular distribution of PACAP-38 and PACAP receptors in the rat brain : Relation to migraine activated regions
  • 2020
  • Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 40:6, s. 527-542
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) occurs as either a 27- or 38-amino acid neuropeptide and belongs to the vasoactive intestinal polypeptide/glucagon/secretin family of peptides. PACAP and vasoactive intestinal polypeptide have a 68% homology of their amino acid sequences and share three B-type G-protein coupled receptors: VPAC1, VPAC2 and PAC1 receptors. Methods/results: The distribution of PACAP-38 and its receptors in the brain is only partly described in the literature. Here, we have performed a study to provide the more general picture of this system in rat brain in order to understand a putative role in primary headaches and partly in relation to the calcitonin gene-related peptide system. We observed a rich expression of PACAP-38 and PAC1 receptor immunoreactivity in many regions throughout the cerebrum, cerebellum and brainstem. The expression pattern points to multiple functions, not least associated with pain and reactions to pain. The expression of VPAC1 and VPAC2 receptor immunoreactivity was very sparse. In several regions such as the cerebral cortex, trigeminal nucleus caudalis, hypothalamus and pons there was a close relation to calcitonin gene-related peptide expression. Conclusion: The findings suggest that the rich supply of PACAP-38 and PAC1 receptors is associated with basic functional responses in the central nervous system (CNS), and there are important close anatomical relations with calcitonin gene-related peptide in CNS regions associated with migraine pathophysiology.
  •  
36.
  • Bayrak Pehlivan, Ilknur, et al. (författare)
  • Bifunctional solar electrocatalytic water splitting using CIGS solar modules and WO3-based electrolyzers
  • 2019
  • Ingår i: EMRS Spring Meeting 2019.
  • Konferensbidrag (refereegranskat)abstract
    • Using energy from the sun to produce a fuel and finally obtaining only water as an exhaust is a promising future technology for renewable energy and environmental sustainability. Solar driven water splitting is a method to produce hydrogen from solar energy. Coupling a solar cell with an electrolyzer is the approach with highest technological readiness. CuInxGa1-xSe2 (CIGS) is here a promising solar cell material for water splitting because it is possible to tune the band gap between 1.0 and 1.7 eV by changing the ratio between Ga and In, thus enabling maximum power point matching with an electrolyzer. Tungsten oxide is known as a photocatalytic material and mainly used for the oxygen evolution reaction in a water splitting process. However, WO3 films also show electrochromic activity together with hydrogen evolution. This result is interesting because it shows that WO3 films can be used as bifunctional materials for both hydrogen and oxygen evolution in water splitting, and provide additional functionalities to the system. In this study, WO3 films coated at different sputtering conditions on Ni foam and indium tin oxide substrates were investigated in the potential range of the hydrogen evolution reaction. The best overpotential of 164 mV vs. RHE at 10 mA/cm2 was obtained for WO3 films on Ni foam in 0.5 M H2SO4. The lowest potential needed for 10 mA/cm2 was measured 1.768 V for the electrolyzers consisting WO3 films on Ni foam as the cathode and non-coated Ni foam as the anode. Optimum solar-to-hydrogen (STH) efficiency of the CIGS solar cell modules and the electrolyzers was examined for different band gaps of the CIGS modules and sputtering conditions of WO3 films. Operation points of the combined system were calculated from the intersection of the voltage-current density curves for the CIGS modules and the electrolyzers. The results showed that the detailed sputtering conditions were not very critical to obtain high STH efficiency, indicating that the system could be robust and easily manufactured. The best-matched band gap of the CIGS was 1.19 eV and the highest STH efficiency of the CIGS driven WO3-based electrolyzers was 12.98 %.
  •  
37.
  • Bayrak Pehlivan, Ilknur, et al. (författare)
  • Optimum Band Gap Energy of ((Ag),Cu)(InGa)Se2 Materials for Combination with NiMo–NiO Catalysts for Thermally Integrated Solar-Driven Water Splitting Applications
  • 2019
  • Ingår i: Energies. - : MDPI AG. - 1996-1073. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Solar-driven water splitting is considered one of the promising future routes to generate fuel in a sustainable way. A carbon-free solar fuel, molecular hydrogen, can here be produced along two different but intimately related routes, photoelectrochemical (PEC) water splitting or photovoltaic electrolysis (PV-electrolysis), where the latter builds on well-established solar cell and electrolysis materials with high efficiency. The PV-electrolysis approach is also possible to construct from an integrated PEC/PV-system avoiding dc-dc converters and enabling heat exchange between the PV and electrolyzer part, to a conventionally wired PV-electrolysis system. In either case, the operating voltage at a certain current needs to be matched with the catalyst system in the electrolysis part. Here, we investigate ((Ag),Cu)(In,Ga)Se-2 ((A)CIGS)-materials with varying Ga-content modules for combination with NiMo-NiO catalysts in alkaline water splitting. The use of (A)CIGS is attractive because of the low cost-to-performance ratio and the possibility to optimize the performance of the system by tuning the band gap of (A)CIGS in contrast to Si technology. The band gap tuning is possible by changing the Ga/(Ga + In) ratio. Optoelectronic properties of the (A)CIGS materials with Ga/(Ga + In) ratios between 0.23 and 0.47 and the voltage and power output from the resulting water splitting modules are reported. Electrolysis is quantified at temperatures between 25 and 60 degrees C, an interval obtainable by varying the thermal heat exchange form a 1-sun illuminated PV module and an electrolyte system. The band gaps of the (A)CIGS thin films were between 1.08 to 1.25 eV and the three-cell module power conversion efficiencies (PCE) ranged from 16.44% with 1.08 eV band gap and 19.04% with 1.17 eV band gap. The highest solar-to-hydrogen (STH) efficiency was 13.33% for the (A)CIGS-NiMo-NiO system with 17.97% module efficiency and electrolysis at 60 degrees C compared to a STH efficiency of 12.98% at 25 degrees C. The increase in STH efficiency with increasing temperature was more notable for lower band gaps as these are closer to the overpotential threshold for performing efficient solar-driven catalysis, while only a modest improvement can be obtained by utilizing thermal exchange for a band gap matched PV-catalysts system. The results show that usage of cost-effective and stable thin film PV materials and earth abundant catalysts can provide STH efficiencies beyond 13% even with PV modules with modest efficiency.
  •  
38.
  • Blixt, Frank W., et al. (författare)
  • MEK/ERK/1/2 sensitive vascular changes coincide with retinal functional deficit, following transient ophthalmic artery occlusion
  • 2019
  • Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835. ; 179, s. 142-149
  • Tidskriftsartikel (refereegranskat)abstract
    • Retinal ischemia remains a major cause of blindness in the world with few acute treatments available. Recent emphasis on retinal vasculature and the ophthalmic artery's vascular properties after ischemia has shown an increase in vasoconstrictive functionality, as previously observed in cerebral arteries following stroke. Specifically, endothelin-1 (ET-1) receptor-mediated vasoconstriction regulated by the MEK/ERK1/2 pathway. In this study, the ophthalmic artery of rats was occluded for 2 h with the middle cerebral artery occlusion model. MEK/ERK1/2 inhibitor U0126 was administered at 0, 6, and 24 h following reperfusion and the functional properties of the ophthalmic artery were evaluated at 48 h post reperfusion. Additionally, retinal function was evaluated at day 1, 4, and 7 after reperfusion. Occlusion of the ophthalmic artery led to a significant increase of endothelin-1 mediated vasoconstriction which can be attenuated by U0126 treatment, most evident at higher ET-1 concentrations of 10−7 M (Emax151.0 ± 22.0% of 60 mM K+), vs non-treated ischemic arteries Emax 212.1 ± 14.7% of 60 mM K+). Retinal function also deteriorated following ischemia and was improved with treatment with a-wave amplitudes of 725 ± 36 μV in control, 560 ± 21 μV in non-treated, and 668 ± 73 μV in U0126 treated at 2 log cd*s/m2 luminance in the acute stages (1 days post-ischemia). Full spontaneous retinal recovery was observed at day 7 regardless of treatment. In conclusion, this is the first study to show a beneficial in vivo effect of U0126 on vascular contractility following ischemia in the ophthalmic artery. Coupled with the knowledge obtained from cerebral vasculature, these results point towards a novel therapeutic approach following ischemia-related injuries to the eye.
  •  
39.
  • Christensen, Simon Topp, et al. (författare)
  • Exploration of Physiological and Pathophysiological Implications of miRNA-143 and miRNA-145 in Cerebral Arteries
  • 2019
  • Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 74:5, s. 409-419
  • Tidskriftsartikel (refereegranskat)abstract
    • Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke with a high short-term mortality rate which leads to cognitive impairments that reduce the quality of life of the majority of patients. The miRNA-143/145 cluster is highly expressed in vascular smooth muscle cells (VSMC) and has been shown to be necessary for differentiation and function, as well as an important determinant for phenotypic modulation/switching of VSMCs in response to vascular injury. We aimed to determine whether miRNA-143 and miRNA-145 are important regulators of phenotypical changes of VSMCs in relation to SAH, as well as establishing their physiological role in the cerebral vasculature. We applied quantitative PCR to study ischemia-induced alterations in the expression of miRNA-143 and miRNA-145, for rat cerebral vasculature, in an ex vivo organ culture model and an in vivo SAH model. To determine the physiological importance, we did myograph studies on basilar and femoral arteries from miRNA-143/145 knockout mice. miRNA-143 and miRNA-145 are not upregulated in the vasculature following our SAH model, despite the upregulation of miR-145 in the organ culture model. Regarding physiological function, miRNA-143 and miRNA-145 are very important for general contractility in cerebral vessels in response to depolarization, angiotensin II, and endothelin-1. Applying an anti-miRNA targeting approach in SAH does not seem to be a feasible approach because miRNA-143 and miRNA-145 are not upregulated following SAH. The knockout mouse data suggest that targeting miRNA-143 and miRNA-145 would lead to a general reduced contractility of the cerebral vasculature and unwanted dedifferentiation of VSMCs.
  •  
40.
  • Christensen, Simon T., et al. (författare)
  • MEK1/2 inhibitor U0126, but not nimodipine, reduces upregulation of cerebrovascular contractile receptors after subarachnoid haemorrhage in rats
  • 2019
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular pathophysiological changes after haemorrhagic stroke, such as phenotypic modulation of the cerebral arteries and cerebral vasospasms, are associated with delayed cerebral ischemia (DCI) and poor outcome. The only currently approved drug treatment shown to reduce the risk of DCI and improve neurologic outcome after aneurysmal subarachnoid haemorrhage (SAH) is nimodipine, a dihydropyridine L-type voltage-gated Ca 2+ channel blocker. MEK1/2 mediated transcriptional upregulation of contractile receptors, including endothelin-1 (ET-1) receptors, has previously been shown to be a factor in the pathology of SAH. The aim of the study was to compare intrathecal and subcutaneous treatment regimens of nimodipine and intrathecal treatment regimens of U0126, a MEK1/2 inhibitor, in a single injection experimental rat SAH model with post 48 h endpoints consisting of wire myography of cerebral arteries, flow cytometry of cerebral arterial tissue and behavioural evaluation. Following ET-1 concentration-response curves, U0126 exposed arteries had a significantly lower ET-1 max than vehicle arteries. Arteries from both the intrathecal- and subcutaneous nimodipine treated animals had significantly higher ET-1 max contractions than the U0126 arteries. Furthermore, Ca 2+ concentration response curves (precontracted with ET-1 and in the presence of nimodipine) showed that nimodipine treatment could result in larger nimodipine insensitive contractions compared to U0126. Flow cytometry showed decreased protein expression of the ET B receptor in U0126 treated cerebral vascular smooth muscle cells compared to vehicle. Only U0126 treatment lowered ET-1 max contractions and ET B receptor levels, as well as decreased the contractions involving nimodipine-insensitive Ca 2+ channels, when compared to both intrathecal and subcutaneous nimodipine treatment. This indicate that targeting gene expression might be a better strategy than blocking specific receptors or ion channels in future treatments of SAH.
  •  
41.
  • Christensen, Simon T., et al. (författare)
  • Pre-clinical effects of highly potent MEK1/2 inhibitors on rat cerebral vasculature after organ culture and subarachnoid haemorrhage
  • 2019
  • Ingår i: Clinical Science. - 0143-5221. ; 133:16, s. 1797-1811
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Aneurysmal subarachnoid haemorrhage (SAH) is a variant of haemorrhagic stroke with a striking 50% mortality rate. In addition to the initial insult, secondary delayed brain injury may occur days after the initial ischemic insult and is associated with vasospasms leading to delayed cerebral ischemia. We have previously shown that the MEK1/2 inhibitor U0126 improves neurological assessment after SAH in rats. Aim: The purpose of the present study was to analyse the impact of a broad selection of high potency MEK1/2 inhibitors in an organ culture model and use the IC50 values obtained from the organ culture to select highly potent inhibitors for pre-clinical in vivo studies. Results: Nine highly potent mitogen activated protein kinase kinase (MEK1/2) inhibitors were screened and the two most potent inhibitors from the organ culture screening, trametinib and PD0325901, were tested in an in vivo experimental rat SAH model with intrathecal injections. Subsequently, the successful inhibitor trametinib was administered intraperitoneally in a second in vivo study. In both regimens, trametinib treatment caused significant reductions in the endothelin-1 induced contractility after SAH, which is believed to be associated with endothelin B receptor up-regulation. Trametinib treated rats showed improved neurological scores, evaluated by the ability to traverse a rotating pole, after induced SAH. Conclusion: The PD0325901 treatment did not improve the neurological score after SAH, nor showed any beneficial therapeutic effect on the contractility, contrasting with the reduction in neurological deficits seen after trametinib treatment. These data show that trametinib might be a potential candidate for treatment of SAH.
  •  
42.
  • Edvinsson, Jacob C.A., et al. (författare)
  • C-fibers may modulate adjacent Aδ-fibers through axon-axon CGRP signaling at nodes of Ranvier in the trigeminal system
  • 2019
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Monoclonal antibodies (mAbs) towards CGRP or the CGRP receptor show good prophylactic antimigraine efficacy. However, their site of action is still elusive. Due to lack of passage of mAbs across the blood-brain barrier the trigeminal system has been suggested a possible site of action because it lacks blood-brain barrier and hence is available to circulating molecules. The trigeminal ganglion (TG) harbors two types of neurons; half of which store CGRP and the rest that express CGRP receptor elements (CLR/RAMP1). METHODS: With specific immunohistochemistry methods, we demonstrated the localization of CGRP, CLR, RAMP1, and their locations related to expression of the paranodal marker contactin-associated protein 1 (CASPR). Furthermore, we studied functional CGRP release separately from the neuron soma and the part with only nerve fibers of the trigeminal ganglion, using an enzyme-linked immunosorbent assay. RESULTS: Antibodies towards CGRP and CLR/RAMP1 bind to two different populations of neurons in the TG and are found in the C- and the myelinated Aδ-fibers, respectively, within the dura mater and in trigeminal ganglion (TG). CASPR staining revealed paranodal areas of the different myelinated fibers inhabiting the TG and dura mater. Double immunostaining with CASPR and RAMP1 or the functional CGRP receptor antibody (AA58) revealed co-localization of the two peptides in the paranodal region which suggests the presence of the CGRP-receptor. Double immunostaining with CGRP and CASPR revealed that thin C-fibers have CGRP-positive boutons which often localize in close proximity to the nodal areas of the CGRP-receptor positive Aδ-fibers. These boutons are pearl-like synaptic structures, and we show CGRP release from fibers dissociated from their neuronal bodies. In addition, we found that adjacent to the CGRP receptor localization in the node of Ranvier there was PKA immunoreactivity (kinase stimulated by cAMP), providing structural possibility to modify conduction activity within the Aδ-fibers. CONCLUSION: We observed a close relationship between the CGRP containing C-fibers and the Aδ-fibers containing the CGRP-receptor elements, suggesting a point of axon-axon interaction for the released CGRP and a site of action for gepants and the novel mAbs to alleviate migraine.
  •  
43.
  • Edvinsson, Lars, et al. (författare)
  • Discovery of CGRP in relation to migraine
  • 2019
  • Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 39:3, s. 331-332
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
44.
  • Edvinsson, Lars, et al. (författare)
  • Does inflammation have a role in migraine?
  • 2019
  • Ingår i: Nature Reviews Neurology. - : Springer Science and Business Media LLC. - 1759-4758 .- 1759-4766.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Migraine is a prevalent disorder, affecting 15.1% of the world’s population. In most cases, the migraine attacks are sporadic; however, some individuals experience a gradual increase in attack frequency over time, and up to 2% of the general population develop chronic migraine. The mechanisms underlying this chronicity are unresolved but are hypothesized to involve a degree of inflammation. In this article, we review the relevant literature related to inflammation and migraine, from the initiation of attacks to chronification. We propose that the increase in migraine frequency leading to chronic migraine involves neurogenic neuroinflammation, possibly entailing increased expression of cytokines via activation of protein kinases in neurons and glial cells of the trigeminovascular system. We present evidence from preclinical research that supports this view and discuss the implications for migraine therapy.
  •  
45.
  •  
46.
  •  
47.
  • Edvinsson, Lars (författare)
  • Role of cgrp in migraine
  • 2019
  • Ingår i: Handbook of Experimental Pharmacology. - Cham : Springer International Publishing. - 1865-0325 .- 0171-2004. ; 255, s. 121-130
  • Bokkapitel (refereegranskat)abstract
    • Migraine is a common neurological disorder that afflicts up to 15% of the adult population in most countries, with predominance in females. It is characterized by episodic, often disabling headache, photophobia and phonophobia, autonomic symptoms (nausea and vomiting), and in a subgroup an aura in the beginning of the attack. Although still debated, many researchers consider migraine to be a disorder in which CNS dysfunction plays a pivotal role while various parts of the trigeminal system are necessary for the expression of associated symptoms. Treatment of migraine has in recent years seen the development of drugs that target the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor. Several of these drugs are now approved for use in frequent episodic and in chronic migraine. CGRP-related therapies offer considerable improvements over existing drugs, as they are the first to be designed specifically to act on the trigeminal pain system: they are more specific and have little or no adverse effects. Small molecule CGRP receptor antagonists, gepants, are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (Eptinezumab, Fremanezumab, and Galcanezumab) or the CGRP receptor (Erenumab) effectively prevent migraine attacks. The neurobiology of CGRP signaling is briefly summarized together with key clinical evidence for the role of CGRP in migraine headache, including the efficacy of CGRP-targeted treatments.
  •  
48.
  • Edvinsson, Marie, et al. (författare)
  • No evidence of Chlamydia pneumoniae in the synovia of patients with osteoarthritis
  • 2019
  • Ingår i: Journal of international medical research. - : Sage Publications. - 0300-0605 .- 1473-2300. ; 47:2, s. 635-640
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Osteoarthritis (OA) is a common cause of disability affecting millions of people of all ages worldwide. The pathogenesis involves an inflammatory component, but the cause of the inflammation remains incompletely understood. The intracellular bacteria Chlamydia trachomatis and C. pneumoniae have been demonstrated in patients with reactive arthritis. Both of these microorganisms can cause chronic and persistent infections, with C. trachomatis being the most common cause of reactive arthritis. This study was performed to investigate the presence of C. pneumoniae in a large number of patients with primary OA.METHODS: The study included 75 patients who underwent total knee arthroplasty. During surgery, a synovial biopsy was performed and synovial fluid drawn. Real-time polymerase chain reaction (PCR) of C. pneumoniae was run on all patients, and real-time PCR of bacterial 16S rDNA was conducted on 30 of the 75 patients to screen for the presence of other bacteria.RESULTS: Real-time PCR showed no evidence of the presence of C. pneumoniae in the patients' specimens, nor were other bacteria detected.CONCLUSIONS: Although an inflammatory component is part of the pathogenesis of OA, we found no evidence indicating that C. pneumoniae is a stimulator of that inflammation.
  •  
49.
  • Frederiksen, Simona D., et al. (författare)
  • Perivascular neurotransmitters : Regulation of cerebral blood flow and role in primary headaches
  • 2019
  • Ingår i: Journal of Cerebral Blood Flow and Metabolism. - 0271-678X. ; 39:4, s. 610-632
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to understand the nature of the relationship between cerebral blood flow (CBF) and primary headaches, we have conducted a literature review with particular emphasis on the role of perivascular neurotransmitters. Primary headaches are in general considered complex polygenic disorders (genetic and environmental influence) with pathophysiological neurovascular alterations. Identified candidate headache genes are associated with neuro- and gliogenesis, vascular development and diseases, and regulation of vascular tone. These findings support a role for the vasculature in primary headache disorders. Moreover, neuronal hyperexcitability and other abnormalities have been observed in primary headaches and related to changes in hemodynamic factors. In particular, this relates to migraine aura and spreading depression. During headache attacks, ganglia such as trigeminal and sphenopalatine (located outside the blood-brain barrier) are variably activated and sensitized which gives rise to vasoactive neurotransmitter release. Sympathetic, parasympathetic and sensory nerves to the cerebral vasculature are activated. During migraine attacks, altered CBF has been observed in brain regions such as the somatosensory cortex, brainstem and thalamus. In regulation of CBF, the individual roles of neurotransmitters are partly known, but much needs to be unraveled with respect to headache disorders.
  •  
50.
  • Haanes, Kristian A., et al. (författare)
  • Exploration of purinergic receptors as potential anti-migraine targets using established pre-clinical migraine models
  • 2019
  • Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 39:11, s. 1421-1434
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The current understanding of mechanisms behind migraine pain has been greatly enhanced with the recent therapies targeting calcitonin gene-related peptide and its receptor. The clinical efficacy of calcitonin gene-related peptide-blocking drugs indicates that, at least in a considerable proportion of patients, calcitonin gene-related peptide is a key molecule in migraine pain. There are several receptors and molecular pathways that can affect the release of and response to calcitonin gene-related peptide. One of these could be purinergic receptors that are involved in nociception, but these are greatly understudied with respect to migraine. Objective: We aimed to explore purinergic receptors as potential anti-migraine targets. Methods: We used the human middle meningeal artery as a proxy for the trigeminal system to screen for possible anti-migraine candidates. The human findings were followed by intravital microscopy and calcitonin gene-related peptide release measurements in rodents. Results: We show that the purinergic P2Y13 receptor fulfills all the features of a potential anti-migraine target. The P2Y13 receptor is expressed in both the human trigeminal ganglion and middle meningeal artery and activation of this receptor causes: a) middle meningeal artery contraction in vitro; b) reduced dural artery dilation following periarterial electrical stimulation in vivo and c) a reduction of CGRP release from both the dura and the trigeminal ganglion in situ. Furthermore, we show that P2X3 receptor activation of the trigeminal ganglion causes calcitonin gene-related peptide release and middle meningeal artery dilation. Conclusion: Both an agonist directed at the P2Y13 receptor and an antagonist of the P2X3 receptor seem to be viable potential anti-migraine therapies.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-50 av 420
Typ av publikation
tidskriftsartikel (353)
konferensbidrag (31)
forskningsöversikt (29)
doktorsavhandling (4)
annan publikation (2)
bokkapitel (1)
visa fler...
visa färre...
Typ av innehåll
refereegranskat (403)
övrigt vetenskapligt/konstnärligt (17)
Författare/redaktör
Edvinsson, Lars (388)
Xu, Cang-Bao (58)
Warfvinge, Karin (39)
Erlinge, David (33)
Ansar, Saema (30)
Malmsjö, Malin (25)
visa fler...
Eftekhari, Sajedeh (19)
Zhang, Yaping (18)
Haanes, Kristian Agm ... (16)
Ahnstedt, Hilda (15)
Stenman, Emelie (14)
Maddahi, Aida (14)
Wackenfors, Angelica (14)
Vikman, Petter (13)
Adner, Mikael (12)
Edvinsson, Tomas, Pr ... (11)
Henriksson, Marie (11)
Tajti, Janos (11)
Edvinsson, Marie-Lou ... (11)
Waldsee, Roya (10)
Grell, Anne Sofie (10)
Cao, Yong-Xiao (10)
Uddman, Erik (9)
Nilsson, Elisabeth (9)
Cao, Lei (9)
Minthon, Lennart (8)
Uddman, Rolf (8)
Gustafson, Lars (8)
Johansson, Sara Elli ... (8)
Edvinsson, Sören, 19 ... (8)
Ingemansson, Richard (7)
Krause, Diana N (7)
Blixt, Frank W. (7)
Hou, Mingyan (7)
Ohlsson, Lena (6)
Bondesson, Susanne (6)
Bygren, Lars Olov, 1 ... (6)
Stolt, Lars (5)
Zhang, Wei (5)
Österlund, Lars, 196 ... (5)
Säveland, Hans (5)
Mostajeran, Maryam (5)
Nilsson, E (5)
Andersson, Sven (5)
Hedner, T (5)
Bayrak Pehlivan, Ilk ... (5)
Broman, Jonas (5)
Radziwon-Balicka, An ... (5)
Erdling, André (5)
Chen, Qingwen (5)
visa färre...
Lärosäte
Lunds universitet (386)
Karolinska Institutet (29)
Uppsala universitet (15)
Umeå universitet (10)
Göteborgs universitet (5)
Örebro universitet (5)
visa fler...
Linnéuniversitetet (3)
Röda Korsets Högskola (3)
Högskolan Kristianstad (2)
Kungliga Tekniska Högskolan (2)
Stockholms universitet (2)
Linköpings universitet (2)
Jönköping University (1)
visa färre...
Språk
Engelska (418)
Svenska (2)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (390)
Naturvetenskap (10)
Teknik (5)
Samhällsvetenskap (3)
Humaniora (1)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy