| 1. |
- Caravaca, April S., et al.
(författare)
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Vagus Nerve Stimulation Reduces Indomethacin-Induced Small Bowel Inflammation
- 2022
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Crohns disease is a chronic, idiopathic condition characterized by intestinal inflammation and debilitating gastrointestinal symptomatology. Previous studies of inflammatory bowel disease (IBD), primarily in colitis, have shown reduced inflammation after electrical or pharmacological activation of the vagus nerve, but the scope and kinetics of this effect are incompletely understood. To investigate this, we studied the effect of electrical vagus nerve stimulation (VNS) in a rat model of indomethacin-induced small intestinal inflammation. 1 min of VNS significantly reduced small bowel total inflammatory lesion area [(mean +/- SEM) sham: 124 +/- 14 mm(2), VNS: 62 +/- 14 mm(2), p = 0.002], intestinal peroxidation and chlorination rates, and intestinal and systemic pro-inflammatory cytokine levels as compared with sham-treated animals after 24 h following indomethacin administration. It was not known whether this observed reduction of inflammation after VNS in intestinal inflammation was mediated by direct innervation of the gut or if the signals are relayed through the spleen. To investigate this, we studied the VNS effect on the small bowel lesions of splenectomized rats and splenic nerve stimulation (SNS) in intact rats. We observed that VNS reduced small bowel inflammation also in splenectomized rats but SNS alone failed to significantly reduce small bowel lesion area. Interestingly, VNS significantly reduced small bowel lesion area for 48 h when indomethacin administration was delayed. Thus, 1 min of electrical activation of the vagus nerve reduced indomethacin-induced intestinal lesion area by a spleen-independent mechanism. The surprisingly long-lasting and spleen-independent effect of VNS on the intestinal response to indomethacin challenge has important implications on our understanding of neural control of intestinal inflammation and its potential translation to improved therapies for IBD.
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| 2. |
- Datta-Chaudhuri, Timir, et al.
(författare)
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The Fourth Bioelectronic Medicine Summit "Technology Targeting Molecular Mechanisms" : current progress, challenges, and charting the future
- 2021
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Ingår i: Bioelectronic medicine. - : BioMed Central. - 2332-8886. ; 7:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- There is a broad and growing interest in Bioelectronic Medicine, a dynamic field that continues to generate new approaches in disease treatment. The fourth bioelectronic medicine summit "Technology targeting molecular mechanisms" took place on September 23 and 24, 2020. This virtual meeting was hosted by the Feinstein Institutes for Medical Research, Northwell Health. The summit called international attention to Bioelectronic Medicine as a platform for new developments in science, technology, and healthcare. The meeting was an arena for exchanging new ideas and seeding potential collaborations involving teams in academia and industry. The summit provided a forum for leaders in the field to discuss current progress, challenges, and future developments in Bioelectronic Medicine. The main topics discussed at the summit are outlined here.
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| 3. |
- Donahue, Mary, et al.
(författare)
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Wireless optoelectronic devices for vagus nerve stimulation in mice
- 2022
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Ingår i: Journal of Neural Engineering. - : IOP Publishing. - 1741-2560 .- 1741-2552. ; 19:6, s. 066031-
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Vagus nerve stimulation (VNS) is a promising approach for the treatment of a wide variety of debilitating conditions, including autoimmune diseases and intractable epilepsy. Much remains to be learned about the molecular mechanisms involved in vagus nerve regulation of organ function. Despite an abundance of well-characterized rodent models of common chronic diseases, currently available technologies are rarely suitable for the required long-term experiments in freely moving animals, particularly experimental mice. Due to challenging anatomical limitations, many relevant experiments require miniaturized, less invasive, and wireless devices for precise stimulation of the vagus nerve and other peripheral nerves of interest. Our objective is to outline possible solutions to this problem by using nongenetic light-based stimulation. Approach. We describe how to design and benchmark new microstimulation devices that are based on transcutaneous photovoltaic stimulation. The approach is to use wired multielectrode cuffs to test different stimulation patterns, and then build photovoltaic stimulators to generate the most optimal patterns. We validate stimulation through heart rate analysis. Main results. A range of different stimulation geometries are explored with large differences in performance. Two types of photovoltaic devices are fabricated to deliver stimulation: photocapacitors and photovoltaic flags. The former is simple and more compact, but has limited efficiency. The photovoltaic flag approach is more elaborate, but highly efficient. Both can be used for wireless actuation of the vagus nerve using light impulses. Significance. These approaches can enable studies in small animals that were previously challenging, such as long-term in vivo studies for mapping functional vagus nerve innervation. This new knowledge may have potential to support clinical translation of VNS for treatment of select inflammatory and neurologic diseases.
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| 4. |
- Hayderi, Assim, 1990-, et al.
(författare)
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RSAD2 is abundant in atherosclerotic plaques and promotes interferon-induced CXCR3-chemokines in human smooth muscle cells
- 2024
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- In atherosclerotic lesions, monocyte-derived macrophages are major source of interferon gamma (IFN-γ), a pleotropic cytokine known to regulate the expression of numerous genes, including the antiviral gene RSAD2. While RSAD2 was reported to be expressed in endothelial cells of human carotid lesions, its significance for the development of atherosclerosis remains utterly unknown. Here, we harnessed publicly available human carotid atherosclerotic data to explore RSAD2 in lesions and employed siRNA-mediated gene-knockdown to investigate its function in IFN-γ-stimulated human aortic smooth muscle cells (hAoSMCs). Silencing RSAD2 in IFN-γ-stimulated hAoSMCs resulted in reduced expression and secretion of key CXCR3-chemokines, CXCL9, CXCL10, and CXCL11. Conditioned medium from RSAD2-deficient hAoSMCs exhibited diminished monocyte attraction in vitro compared to conditioned medium from control cells. Furthermore, RSAD2 transcript was elevated in carotid lesions where it was expressed by several different cell types, including endothelial cells, macrophages and smooth muscle cells. Interestingly, RSAD2 displayed significant correlations with CXCL10 (r = 0.45, p = 0.010) and CXCL11 (r = 0.53, p = 0.002) in human carotid lesions. Combining our findings, we uncover a novel role for RSAD2 in hAoSMCs, which could potentially contribute to monocyte recruitment in the context of atherosclerosis.
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| 5. |
- Kumawat, Ashok Kumar, 1982-, et al.
(författare)
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Inhibition of IL17A Using an Affibody Molecule Attenuates Inflammation in ApoE-Deficient Mice
- 2022
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Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The balance between pro- and anti-inflammatory cytokines released by immune and non-immune cells plays a decisive role in the progression of atherosclerosis. Interleukin (IL)-17A has been shown to accelerate atherosclerosis. In this study, we investigated the effect on pro-inflammatory mediators and atherosclerosis development of an Affibody molecule that targets IL17A. Affibody molecule neutralizing IL17A, or sham were administered in vitro to human aortic smooth muscle cells (HAoSMCs) and murine NIH/3T3 fibroblasts and in vivo to atherosclerosis-prone, hyperlipidaemic ApoE(-/-) mice. Levels of mediators of inflammation and development of atherosclerosis were compared between treatments. Exposure of human smooth muscle cells and murine NIH/3T3 fibroblasts in vitro to alpha IL-17A Affibody molecule markedly reduced IL6 and CXCL1 release in supernatants compared with sham exposure. Treatment of ApoE(-/-) mice with alpha IL-17A Affibody molecule significantly reduced plasma protein levels of CXCL1, CCL2, CCL3, HGF, PDGFB, MAP2K6, QDPR, and splenocyte mRNA levels of Ccxl1, Il6, and Ccl20 compared with sham exposure. There was no significant difference in atherosclerosis burden between the groups. In conclusion, administration of alpha IL17A Affibody molecule reduced levels of pro-inflammatory mediators and attenuated inflammation in ApoE(-/-) mice.
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| 6. |
- Olofsson, Peder S., et al.
(författare)
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Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase
- 2016
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Ingår i: Nature Biotechnology. - : Nature Publishing Group. - 1087-0156 .- 1546-1696. ; 34:10, s. 1066-1071
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been determined. We previously showed that CD4(+) T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals(1). Here we show that these CD4(+)CD44(hi)CD62L(Io) T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 T-ChAT). Mice lacking ChAT expression in CD4(+) cells have elevated arterial blood pressure, compared to littermate controls. Jurkat T cells overexpressing ChAT (JT(ChAT)) decreased blood pressure when infused into mice. Co-incubation of JT(ChAT) and endothelial cells increased endothelial cell levels of phosphorylated endothelial nitric oxide synthase, and of nitrates and nitrites in conditioned media, indicating increased release of the potent vasorelaxant nitric oxide. The isolation and characterization of CD4 T-ChAT cells will enable analysis of the role of these cells in hypotension and hypertension, and may suggest novel therapeutic strategies by targeting cell-mediated vasorelaxation.
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| 7. |
- Padinhare, Harikesh, et al.
(författare)
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Ion-tunable antiambipolarity in mixed ion-electron conducting polymers enables biorealistic organic electrochemical neurons
- 2023
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Ingår i: Nature Materials. - : NATURE PORTFOLIO. - 1476-1122 .- 1476-4660. ; 22, s. 242-248
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Tidskriftsartikel (refereegranskat)abstract
- Biointegrated neuromorphic hardware holds promise for new protocols to record/regulate signalling in biological systems. Making such artificial neural circuits successful requires minimal device/circuit complexity and ion-based operating mechanisms akin to those found in biology. Artificial spiking neurons, based on silicon-based complementary metal-oxide semiconductors or negative differential resistance device circuits, can emulate several neural features but are complicated to fabricate, not biocompatible and lack ion-/chemical-based modulation features. Here we report a biorealistic conductance-based organic electrochemical neuron (c-OECN) using a mixed ion-electron conducting ladder-type polymer with stable ion-tunable antiambipolarity. The latter is used to emulate the activation/inactivation of sodium channels and delayed activation of potassium channels of biological neurons. These c-OECNs can spike at bioplausible frequencies nearing 100 Hz, emulate most critical biological neural features, demonstrate stochastic spiking and enable neurotransmitter-/amino acid-/ion-based spiking modulation, which is then used to stimulate biological nerves in vivo. These combined features are impossible to achieve using previous technologies.
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| 8. |
- Söderström, Leif, et al.
(författare)
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Increased carotid artery lesion inflammation upon treatment with the CD137 agonistic antibody 2A
- 2017
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Ingår i: Circulation Journal. - 1346-9843. ; 81:12, s. 1945-1952
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increased inflammatory activity destabilizes the atherosclerotic lesion and may lead to atherothrombosis and symptomatic cardiovascular disease. Co-stimulatory molecules, such as CD137, are key regulators of inflammation, and CD137 activity regulates inflammation in experimental atherosclerosis. Here, we hypothesized that CD137 activation promotes carotid artery inflammation and atherothrombosis. Methods and Results: In a model of inducible atherothrombosis with surgical ligation of the right carotid artery and a subsequent placement of a polyethene cuff, elevated levels of CD137 and CD137 ligand mRNA in atherothrombotic vs. non-atherothrombotic murine carotid lesions was observed. Mice treated with the CD137 agonistic antibody 2A showed signs of increased inflammation in the aorta and a higher proportion of CD8+ T cells in spleen and blood. In carotid lesions of 2A-treated mice, significantly higher counts of CD8+ and major histocompatibility (MHC)-class II molecule I-Ab+ cells were observed. Treatment with the CD137 agonistic antibody 2A did not significantly affect the atherothrombosis frequency in 16-week-old mice in this model. Conclusions: Levels of CD137 and CD137 ligand mRNA were higher in advanced atherosclerotic disease compared to control vessels, and treatment with the CD137 agonistic antibody 2A, in a murine model for inducible atherothrombosis promoted vascular inflammation, but had no significant effect on atherothrombosis frequency at this early disease stage.
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| 9. |
- Botzanowski, Boris, et al.
(författare)
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Noninvasive Stimulation of Peripheral Nerves using Temporally-Interfering Electrical Fields
- 2022
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Ingår i: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659. ; 11:17
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Tidskriftsartikel (refereegranskat)abstract
- Electrical stimulation of peripheral nerves is a cornerstone of bioelectronic medicine. Effective ways to accomplish peripheral nerve stimulation (PNS) noninvasively without surgically implanted devices are enabling for fundamental research and clinical translation. Here, it is demonstrated how relatively high-frequency sine-wave carriers (3 kHz) emitted by two pairs of cutaneous electrodes can temporally interfere at deep peripheral nerve targets. The effective stimulation frequency is equal to the offset frequency (0.5 - 4 Hz) between the two carriers. This principle of temporal interference nerve stimulation (TINS) in vivo using the murine sciatic nerve model is validated. Effective actuation is delivered at significantly lower current amplitudes than standard transcutaneous electrical stimulation. Further, how flexible and conformable on-skin multielectrode arrays can facilitate precise alignment of TINS onto a nerve is demonstrated. This method is simple, relying on the repurposing of existing clinically-approved hardware. TINS opens the possibility of precise noninvasive stimulation with depth and efficiency previously impossible with transcutaneous techniques.
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| 10. |
- Brück, Emily, et al.
(författare)
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Lack of clinically relevant correlation between subjective and objective cognitive function in ICU survivors : a prospective 12-month follow-up study
- 2019
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCognitive impairment and psychological distress are common in intensive care unit (ICU) survivors. Early identification of affected individuals is important, so intervention and treatment can be utilized at an early stage. Cognitive Failures Questionnaire (CFQ) is commonly used to screen for subjective cognitive function, but it is unclear whether CFQ scores correlate to objective cognitive function in this population.MethodsBetween 2014 and 2018, 100 ICU survivors aged 18–70 years from the general ICU at the Karolinska University Hospital, Solna, were included in the study. Out of these, 58 patients completed follow-up at 3 months after ICU discharge, 51 at 6 months, and 45 at 12 months. Follow-up included objective cognitive function testing using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and subjective cognitive function testing with the self-rating Cognitive Failures Questionnaire (CFQ), as well as psychological self-rating with the Post-Traumatic Stress Symptoms Scale-10 (PTSS-10) and Hospital Anxiety and Depression Scale (HADS).ResultsThe prevalence of cognitive impairment as measured by four selected CANTAB tests was 34% at 3 months after discharge, 18% at 6 months, and 16% at 12 months. There was a lack of significant correlation between CANTAB scores and CFQ scores at 3 months (r = − 0.134–0.207, p > 0.05), at 6 months (r = − 0.106–0.257, p > 0.05), and at 12 months after discharge (r = − 0.070–0.109, p > 0.05). Correlations between CFQ and PTSS-10 scores and HADS scores, respectively, were significant over the follow-up period (r = 0.372–0.710, p ≤ 0.001–0.023). In contrast, CANTAB test scores showed a weak correlation with PTSS-10 and HADS scores, respectively, at 3 months only (r = − 0.319–0.348, p = 0.008–0.015).ConclusionWe found no clinically relevant correlation between subjective and objective cognitive function in this cohort of ICU survivors, while subjective cognitive function correlated significantly with psychological symptoms throughout the follow-up period. Treatment and evaluation of ICU survivors’ recovery need to consider both subjective and objective aspects of cognitive impairment, and subjective reports must be interpreted with caution as an indicator of objective cognitive function.
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