| 1. |
- Augestad, Ingrid Lovise, et al.
(författare)
-
Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat
- 2017
-
Ingår i: Neurochemical Research. - : SPRINGER/PLENUM PUBLISHERS. - 0364-3190 .- 1573-6903. ; 42:6, s. 1599-1609
-
Tidskriftsartikel (refereegranskat)abstract
- Effective transplant-mediated repair of ischemic brain lesions entails extensive tissue remodeling, especially in the ischemic core. Neural stem cells (NSCs) are promising reparative candidates for stroke induced lesions, however, their survival and integration with the host-tissue post-transplantation is poor. In this study, we address this challenge by testing whether co-grafting of NSCs with olfactory ensheathing cells (OECs), a special type of glia with proven neuroprotective, immunomodulatory, and angiogenic effects, can promote graft survival and host tissue remodelling. Transient focal cerebral ischemia was induced in adult rats by a 60-min middle cerebral artery occlusion (MCAo) followed by reperfusion. Ischemic lesions were verified by neurological testing and magnetic resonance imaging. Transplantation into the globus pallidus of NSCs alone or in combination with OECs was performed at two weeks post-MCAo, followed by histological analyses at three weeks post-transplantation. We found evidence of extensive vascular remodelling in the ischemic core as well as evidence of NSC motility away from the graft and into the infarct border in severely lesioned animals co-grafted with OECs. These findings support a possible role of OECs as part of an in situ tissue engineering paradigm for transplant mediated repair of ischemic brain lesions.
|
|
| 2. |
- Bandyopadhyay, Sulalit, et al.
(författare)
-
Growing gold nanostructures for shape-selective cellular uptake
- 2018
-
Ingår i: Nanoscale Research Letters. - : SpringerOpen. - 1931-7573 .- 1556-276X. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- With development in the synthesis of shape- and size-dependent gold (Au) nanostructures (NSs) and their applications in nanomedicine, one of the biggest challenges is to understand the interaction of these shapes with cancer cells. Herein, we study the interaction of Au NSs of five different shapes with glioblastoma-astrocytoma cells. Three different shapes (nanorods, tetrahexahedra, and bipyramids), possessing tunable optical properties, have been synthesized by a single-step seed-mediated growth approach employing binary surfactant mixtures of CTAB and a secondary surfactant By the use of two-step seed-mediated approach, we obtained new NSs, named nanomakura (Makura is a Japanese word used for pillow) which is reported for the first time here. Spherical Au nanoparticles were prepared by the Turkevich method. To study NS-cell interactions, we functionalized the NSs using thiolated PEG followed by 11-Mercaptoundecanoic acid. The influence of shape and concentration of NSs on the cytotoxicity were assessed with a LIVE/DEAD assay in glioblastoma-astrocytoma cells. Furthermore, the time-dependent uptake of nanomakura was studied with TEM. Our results indicate that unlike the other shapes studied here, the nanomakura were taken up both via receptor-mediated endocytosis and macropinocytosis. Thus, from our library of different NSs with similar surface functionality, the shape is found to be an important parameter for cellular uptake.
|
|
| 3. |
- Bandyopadhyay, Sulalit, et al.
(författare)
-
Synthesis and in vitro cellular interactions of superparamagnetic iron nanoparticles with a crystalline gold shell
- 2014
-
Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 316, s. 171-178
-
Tidskriftsartikel (refereegranskat)abstract
- Fe@Au core-shell nanoparticles (NPs) exhibit multiple functionalities enabling their effective use in applications such as medical imaging and drug delivery. In this work, a novel synthetic method was developed and optimized for the synthesis of highly stable, monodisperse Fe@Au NPs of average diameter similar to 24 nm exhibiting magneto-plasmonic characteristics. Fe@Au NPs were characterized by a wide range of experimental techniques, including scanning (transmission) electron microscopy (S(T)EM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDX), dynamic light scattering (DLS) and UV-vis spectroscopy. The formed particles comprise an amorphous iron core with a crystalline Au shell of tunable thickness, and retain the superparamagnetic properties at room temperature after formation of a crystalline Au shell. After surface modification, PEGylated Fe@Au NPs were used for in vitro studies on olfactory ensheathing cells (OECs) and human neural stem cells (hNSCs). No adverse effects of the Fe@Au particles were observed post-labeling, both cell types retaining normal morphology, viability, proliferation, and motility. It can be concluded that no appreciable toxic effects on both cell types, coupled with multifunctionality and chemical stability make them ideal candidates for therapeutic as well as diagnostic applications.
|
|
| 4. |
- Bauer, Ulrich Stefan, et al.
(författare)
-
Validation of Functional Connectivity of Engineered Neuromuscular Junction With Recombinant Monosynaptic Pseudotyped ΔG-Rabies Virus Tracing
- 2022
-
Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media S.A.. - 1662-5145. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Current preclinical models of neurodegenerative disease, such as amyotrophic lateral sclerosis (ALS), can significantly benefit from in vitro neuroengineering approaches that enable the selective study and manipulation of neurons, networks, and functional units of interest. Custom-designed compartmentalized microfluidic culture systems enable the co-culture of different relevant cell types in interconnected but fluidically isolated microenvironments. Such systems can thus be applied for ALS disease modeling, as they enable the recapitulation and study of neuromuscular junctions (NMJ) through co-culturing of motor neurons and muscle cells in separate, but interconnected compartments. These in vitro systems are particularly relevant for investigations of mechanistic aspects of the ALS pathological cascade in engineered NMJ, as progressive loss of NMJ functionality may constitute one of the hallmarks of disease related pathology at early onset, in line with the dying back hypothesis. In such models, ability to test whether motor neuron degeneration in ALS starts at the nerve terminal or at the NMJ and retrogradely progresses to the motor neuron cell body largely relies on robust methods for verification of engineered NMJ functionality. In this study, we demonstrate the functionality of engineered NMJs within a microfluidic chip with a differentially perturbable microenvironment using a designer pseudotyped ΔG-rabies virus for retrograde monosynaptic tracing.
|
|
| 5. |
- Bjorkli, Christiana, et al.
(författare)
-
Bridging the Gap Between Fluid Biomarkers for Alzheimer's Disease, Model Systems, and Patients
- 2020
-
Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of two proteins in fibrillar form: amyloid-β (Aβ) and tau. Despite decades of intensive research, we cannot yet pinpoint the exact cause of the disease or unequivocally determine the exact mechanism(s) underlying its progression. This confounds early diagnosis and treatment of the disease. Cerebrospinal fluid (CSF) biomarkers, which can reveal ongoing biochemical changes in the brain, can help monitor developing AD pathology prior to clinical diagnosis. Here we review preclinical and clinical investigations of commonly used biomarkers in animals and patients with AD, which can bridge translation from model systems into the clinic. The core AD biomarkers have been found to translate well across species, whereas biomarkers of neuroinflammation translate to a lesser extent. Nevertheless, there is no absolute equivalence between biomarkers in human AD patients and those examined in preclinical models in terms of revealing key pathological hallmarks of the disease. In this review, we provide an overview of current but also novel AD biomarkers and how they relate to key constituents of the pathological cascade, highlighting confounding factors and pitfalls in interpretation, and also provide recommendations for standardized procedures during sample collection to enhance the translational validity of preclinical AD models.
|
|
| 6. |
- Bjorkli, Christiana, et al.
(författare)
-
Combined targeting of pathways regulating synaptic formation and autophagy attenuates Alzheimer’s disease pathology in mice
- 2022
-
Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- All drug trials completed to date have fallen short of meeting the clinical endpoint of significantly slowing cognitive decline in Alzheimer’s disease (AD) patients. In this study, we repurposed two FDA-approved drugs, Fasudil and Lonafarnib, targeting synaptic formation (i.e., Wnt signaling) and cellular clearance (i.e., autophagic) pathways respectively, to test their therapeutic potential for attenuating AD-related pathology. We characterized our 3xTg AD mouse colony to select timepoints for separate and combinatorial treatment of both drugs while collecting cerebrospinal fluid (CSF) using an optimized microdialysis method. We found that treatment with Fasudil reduced Aβ at early and later stages of AD, whereas administration of Lonafarnib had no effect on Aβ, but did reduce tau, at early stages of the disease. Induction of autophagy led to increased size of amyloid plaques when administered at late phases of the disease. We show that combinatorial treatment with both drugs was effective at reducing intraneuronal Aβ and led to improved cognitive performance in mice. These findings lend support to regulating Wnt and autophagic pathways in order to attenuate AD-related pathology.
|
|
| 7. |
- Fiskum, Vegard, et al.
(författare)
-
Silencing of Activity During Hypoxia Improves Functional Outcomes in Motor Neuron Networks in vitro
- 2021
-
Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media S.A.. - 1662-5145. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of hypoxia, or reduced oxygen supply, to brain tissue can be disastrous, leading to extensive loss of function. Deoxygenated tissue becomes unable to maintain healthy metabolism, which leads to increased production of reactive oxygen species (ROS) and loss of calcium homoeostasis, with damaging downstream effects. Neurons are a highly energy demanding cell type, and as such they are highly sensitive to reductions in oxygenation and some types of neurons such as motor neurons are even more susceptible to hypoxic damage. In addition to the immediate deleterious effects hypoxia can have on neurons, there can be delayed effects which lead to increased risk of developing neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), even if no immediate consequences are apparent. Furthermore, impairment of the function of various hypoxia-responsive factors has been shown to increase the risk of developing several neurodegenerative disorders. Longitudinal assessment of electrophysiological network activity is underutilised in assessing the effects of hypoxia on neurons and how their activity and communication change over time following a hypoxic challenge. This study utilised multielectrode arrays and motor neuron networks to study the response to hypoxia and the subsequent development of the neuronal activity over time, as well as the effect of silencing network activity during the hypoxic challenge. We found that motor neuron networks exposed to hypoxic challenge exhibited a delayed fluctuation in multiple network activity parameters compared to normoxic networks. Silencing of activity during the hypoxic challenge leads to maintained bursting activity, suggesting that functional outcomes are better maintained in these networks and that there are activity-dependent mechanisms involved in the network damage following hypoxia.
|
|
| 8. |
- Hanssen, Katrine Sjaastad, et al.
(författare)
-
Dissection and culturing of adult lateral entorhinal cortex layer II neurons from APP/PS1 Alzheimer model mice
- 2023
-
Ingår i: Journal of Neuroscience Methods. - : Elsevier. - 0165-0270 .- 1872-678X. ; 390
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Primary neuronal cultures enable cell-biological studies of Alzheimer's disease (AD), albeit typically non-neuron-specific. The first cortical neurons affected in AD reside in layer II of the lateralmost part of the entorhinal cortex, and they undergo early accumulation of intracellular amyloid-β, form subsequent tau pathology, and start degenerating pre-symptomatically. These vulnerable entorhinal neurons uniquely express the glycoprotein reelin and provide selective inputs to the hippocampal memory system. Gaining a more direct access to study these neurons is therefore highly relevant.New method: We demonstrate a methodological approach for dissection and long-term culturing of adult lateral entorhinal layer II-neurons from AD-model mice.Results: We maintain adult dissected lateralmost entorhinal layer II-neurons beyond two months in culture. We show that they express neuronal markers, and that they are electrophysiologically active by 15 days in vitro and continuing beyond 2 months.Comparison with existing methods: Primary neurons are typically harvested from embryonic or early postnatal brains because such neurons are easier to culture compared to adult neurons. Methods to culture adult primary neurons have been reported, however, to our knowledge, culturing of adult entorhinal neuron-type specific primary neurons from AD-model animals have not been reported.Conclusions: Our methodological approach offers a window to study initial pathological changes in the AD disease-cascade. This includes the study of proteinopathy, single-neuron changes, and network-level dysfunction.
|
|
| 9. |
- McDonagh, Birgitte H, et al.
(författare)
-
Controlling the self-assembly and optical properties of gold nanoclusters and gold nanoparticles biomineralized with bovine serum albumin
- 2015
-
Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 5:122, s. 101101-101109
-
Tidskriftsartikel (refereegranskat)abstract
- While the size-dependent optical properties of BSA-stabilized gold nanoclusters are well known, the timedependent growth mechanism remains to be described. Herein, we systematically compare two synthesis methods with and without ascorbic acid, and show that tuning of BSA-stabilized gold nanoclusters (AuNCs) of different sizes can be performed without the aid of an extrinsic reducing agent and with good reproducibility. We also show that adding ascorbic acid yields larger BSA-stabilized gold nanoparticles (AuNPs), and that AuNPs can only form above a threshold gold precursor concentration. Using computed tomography, we describe how these biomineralized AuNPs show size-dependent X-ray attenuation. Growth of BSA-stabilized AuNCs and AuNPs, over a range of gold precursor concentrations, was followed with steady-state fluorescence and UV-vis spectroscopy for one week, constituting the first study of its kind. Based on our results, we propose a mechanism for BSA-stabilization of AuNCs and AuNPs that can further aid in selective growth of discrete AuNCs and AuNPs.
|
|
| 10. |
- McDonagh, Birgitte Hjelmeland, et al.
(författare)
-
L-DOPA-Coated Manganese Oxide Nanoparticles as Dual MRI Contrast Agents and Drug-Delivery Vehicles
- 2016
-
Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 12:3, s. 301-306
-
Tidskriftsartikel (refereegranskat)abstract
- Manganese oxide nanoparticles (MONPs) are capable of time-dependent magnetic resonance imaging contrast switching as well as releasing a surface-bound drug. MONPs give T2/T2* contrast, but dissolve and release T1-active Mn2+ and l-3,4-dihydroxyphenylalanine. Complementary images are acquired with a single contrast agent, and applications toward Parkinson's disease are suggested.
|
|
