| 1. |
- Augestad, Ingrid Lovise, et al.
(författare)
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Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat
- 2017
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Ingår i: Neurochemical Research. - : SPRINGER/PLENUM PUBLISHERS. - 0364-3190 .- 1573-6903. ; 42:6, s. 1599-1609
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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.
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| 2. |
- Bandyopadhyay, Sulalit, et al.
(författare)
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Growing gold nanostructures for shape-selective cellular uptake
- 2018
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Ingår i: Nanoscale Research Letters. - : SpringerOpen. - 1931-7573 .- 1556-276X. ; 13
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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.
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| 3. |
- Bandyopadhyay, Sulalit, et al.
(författare)
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Synthesis and in vitro cellular interactions of superparamagnetic iron nanoparticles with a crystalline gold shell
- 2014
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Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 316, s. 171-178
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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.
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| 4. |
- Bauer, Ulrich Stefan, et al.
(författare)
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Validation of Functional Connectivity of Engineered Neuromuscular Junction With Recombinant Monosynaptic Pseudotyped ΔG-Rabies Virus Tracing
- 2022
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media S.A.. - 1662-5145. ; 16
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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.
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| 5. |
- Bjorkli, Christiana, et al.
(författare)
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Bridging the Gap Between Fluid Biomarkers for Alzheimer's Disease, Model Systems, and Patients
- 2020
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 12
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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.
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| 6. |
- Bjorkli, Christiana, et al.
(författare)
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Combined targeting of pathways regulating synaptic formation and autophagy attenuates Alzheimer’s disease pathology in mice
- 2022
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 13
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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.
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| 7. |
- Fiskum, Vegard, et al.
(författare)
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Silencing of Activity During Hypoxia Improves Functional Outcomes in Motor Neuron Networks in vitro
- 2021
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media S.A.. - 1662-5145. ; 15
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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.
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| 8. |
- Hanssen, Katrine Sjaastad, et al.
(författare)
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Dissection and culturing of adult lateral entorhinal cortex layer II neurons from APP/PS1 Alzheimer model mice
- 2023
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Ingår i: Journal of Neuroscience Methods. - : Elsevier. - 0165-0270 .- 1872-678X. ; 390
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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.
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| 9. |
- McDonagh, Birgitte H, et al.
(författare)
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Controlling the self-assembly and optical properties of gold nanoclusters and gold nanoparticles biomineralized with bovine serum albumin
- 2015
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 5:122, s. 101101-101109
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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.
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| 10. |
- McDonagh, Birgitte Hjelmeland, et al.
(författare)
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L-DOPA-Coated Manganese Oxide Nanoparticles as Dual MRI Contrast Agents and Drug-Delivery Vehicles
- 2016
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Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 12:3, s. 301-306
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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.
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| 11. |
- McDonagh, Birgitte H., et al.
(författare)
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Self-assembly and characterization of transferrin-gold nanoconstructs and their interaction with bio-interfaces
- 2015
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 7:17, s. 8062-8070
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Tidskriftsartikel (refereegranskat)abstract
- Transferrin (Tf) conjugated to gold nanoparticles and clusters combine the protein's site-specific receptor targeting capabilities with the optical properties imparted by the nano-sized gold. We have described two different synthesis protocols, one yielding fluorescent Tf-stabilized gold nanoclusters (AuNCs) and one yielding Tf-stabilized gold nanoparticles that exhibit localized surface plasmon resonance. We demonstrate that the synthetic route employed has a large influence both on the gold nanostructure formed, and also on the structural integrity of the protein. A slight protein unfolding allows stronger interaction with lipids, and was found to significantly perturb lipid monolayers. Interactions between the protein-gold nanostructures and three different cell types were also assessed, indicating that the enhanced membrane affinity may be attributed to intercellular membrane differences.
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| 12. |
- Podobinska, Martyna, et al.
(författare)
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Epigenetic Modulation of Stem Cells in Neurodevelopment : The Role of Methylation and Acetylation
- 2017
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media S.A.. - 1662-5102. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The coordinated development of the nervous system requires fidelity in the expression of specific genes determining the different neural cell phenotypes. Stem cell fate decisions during neurodevelopment are strictly correlated with their epigenetic status. The epigenetic regulatory processes, such as DNA methylation and histone modifications discussed in this review article, may impact both neural stem cell (NSC) self-renewal and differentiation and thus play an important role in neurodevelopment. At the same time, stem cell decisions regarding fate commitment and differentiation are highly dependent on the temporospatial expression of specific genes contingent on the developmental stage of the nervous system. An interplay between the above, as well as basic cell processes, such as transcription regulation, DNA replication, cell cycle regulation and DNA repair therefore determine the accuracy and function of neuronal connections. This may significantly impact embryonic health and development as well as cognitive processes such as neuroplasticity and memory formation later in the adult.
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| 13. |
- Sandvig, Axel, et al.
(författare)
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Axonal tracing of the normal and regenerating visual pathway of mouse, rat, frog, and fish using manganese-enhanced MRI (MEMRI)
- 2011
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Ingår i: Journal of Magnetic Resonance Imaging. - Chicago, IL : Society for Magnetic Resonance Imaging. - 1053-1807 .- 1522-2586. ; 34:3, s. 670-675
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess optic nerve (ON) regeneration after injury by applying manganese-enhanced MRI (MEMRI) in a study of comparative physiology between nonregenerating rat and mouse species and regenerating frog and fish species.Materials and Methods: The normal visual projections of rats, mice, frogs, and fish was visualized by intravitreal MnCl(2) injection followed by MRI. Rats and mice with ON crush (ONC) were divided into nonregenerating (ONC only), and regenerating animals with peripheral nerve graft (ONC+PNG; rats) or lens injury (ONC+LI; mice) and monitored by MEMRI at 1 and 20 days post-lesion (dpl). Frog and fish with ON transection (ONT) were monitored by MEMRI up to 6 months postlesion (mpl).Results: Signal intensity profiles of the Mn(2+)-enhanced ON were consistent with ON regeneration in the ONC+PNG and ONC+LI rat and mice groups, respectively, compared with the nonregenerating ONC groups. Furthermore, signal intensity profiles of the Mn(2+)-enhanced ON obtained between 1 mpl and 6 mpl in the fish and frog groups, respectively, were consistent with spontaneous, complete ON regeneration.Conclusion: Taken together, these results demonstrate that MEMRI is a viable method for serial, in vivo monitoring of normal, induced, and spontaneously regenerating optic nerve axons in different species.
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| 14. |
- Sandvig, Axel, et al.
(författare)
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Connectomics of morphogenetically engineered neurons as a predictor of functional integration in the ischemic brain
- 2019
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Recent advances in cell reprogramming technologies enable the in vitro generation of theoretically unlimited numbers of cells, including cells of neural lineage and specific neuronal subtypes from human, including patient-specific, somatic cells. Similarly, as demonstrated in recent animal studies, by applying morphogenetic neuroengineering principles in situ, it is possible to reprogram resident brain cells to the desired phenotype. These developments open new exciting possibilities for cell replacement therapy in stroke, albeit not without caveats. Main challenges include the successful integration of engineered cells in the ischemic brain to promote functional restoration as well as the fact that the underlying mechanisms of action are not fully understood. In this review, we aim to provide new insights to the above in the context of connectomics of morphogenetically engineered neural networks. Specifically, we discuss the relevance of combining advanced interdisciplinary approaches to: validate the functionality of engineered neurons by studying their self-organizing behavior into neural networks as well as responses to stroke-related pathology in vitro; derive structural and functional connectomes from these networks in healthy and perturbed conditions; and identify and extract key elements regulating neural network dynamics, which might predict the behavior of grafted engineered neurons post-transplantation in the stroke-injured brain.
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| 15. |
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| 16. |
- Sandvig, Ioanna, et al.
(författare)
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In vivo MRI of olfactory ensheathing cell grafts and regenerating axons in transplant mediated repair of the adult rat optic nerve
- 2012
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Ingår i: NMR in Biomedicine. - Malden, MA, USA : John Wiley & Sons. - 0952-3480 .- 1099-1492. ; 25:4, s. 620-631
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to use magnetic resonance imaging (MRI) as a tool for monitoring transplant-mediated repair of the adult rat visual pathway. We labelled rat olfactory ensheathing cells (OECs) using micron-sized particles of iron oxide (MPIO) and transplanted them by: i) intravitreal injection (ivit) and ii) intra-optic nerve (ON) injection (iON) in adult rats with ON crush (ONC) injury. We applied T2-weighted MRI and manganese-enhanced MRI (MEMRI) to visualise transplanted cells and ON axons at specific times after injury and cell engraftment. Our findings demonstrate that ivit MPIO-labelled OECs are unequivocally detected by T2-weighted MRI in vivo and that the T1-weighted 3D FLASH sequence applied for MEMRI facilitates simultaneous visualisation of Mn2+-enhanced regenerating retinal ganglion cell (RGC) axons and MPIO-labelled OEC grafts. Furthermore, analysis of MRI data and ultrastructural findings supports the hypothesis that iON OEC transplants mediate regeneration and remyelination of RGC axons post injury.
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| 17. |
- Sandvig, Ioanna, et al.
(författare)
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Labelling of olfactory ensheathing cells with micron-sized particles of iron oxide and detection by MRI
- 2012
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Ingår i: Contrast Media & Molecular Imaging. - Hoboken, NJ : Wiley-Blackwell. - 1555-4309 .- 1555-4317. ; 7:4, s. 403-410
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Tidskriftsartikel (refereegranskat)abstract
- A crucial issue in transplant-mediated repair of the damaged central nervous system (CNS) is serial non-invasive imaging of the transplanted cells, which has led to interest in the application of magnetic resonance imaging (MRI) combined with designated intracellular magnetic labels for cell tracking. Micron-sized particles of iron oxide (MPIO) have been successfully used to track cells by MRI, yet there is relatively little known about either their suitability for efficient labelling of specific cell types, or their effects on cell viability. The purpose of this study was to develop a suitable MPIO labelling protocol for olfactory ensheathing cells (OECs), a type of glia used to promote the regeneration of CNS axons after transplantation into the injured CNS. Here, we demonstrate an OEC labelling efficiency of >90% with an MPIO incubation time as short as 6?h, enabling intracellular particle uptake for single-cell detection by MRI without affecting cell proliferation, migration and viability. Moreover, MPIO are resolvable in OECs transplanted into the vitreous body of adult rat eyes, providing the first detailed protocol for efficient and safe MPIO labelling of OECs for non-invasive MRI tracking of transplanted OECs in real time for use in studies of CNS repair and axon regeneration. Copyright (c) 2012 John Wiley & Sons, Ltd.
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| 18. |
- Sandvig, Ioanna, et al.
(författare)
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Neuroplasticity in stroke recovery : The role of microglia in engaging and modifying synapses and networks
- 2018
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Ingår i: European Journal of Neuroscience. - : John Wiley & Sons. - 0953-816X .- 1460-9568. ; 47:12, s. 1414-1428
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Tidskriftsartikel (refereegranskat)abstract
- Neuroplasticity after ischaemic injury involves both spontaneous rewiring of neural networks and circuits as well as functional responses in neurogenic niches. These events involve complex interactions with activated microglia, which evolve in a dynamic manner over time. Although the exact mechanisms underlying these interactions remain poorly understood, increasing experimental evidence suggests a determining role of pro- and anti-inflammatory microglial activation profiles in shaping both synaptogenesis and neurogenesis. While the inflammatory response of microglia was thought to be detrimental, a more complex profile of the role of microglia in tissue remodelling is emerging. Experimental evidence suggests that microglia in response to injury can rapidly modify neuronal activity and modulate synaptic function, as well as be beneficial for the proliferation and integration of neural progenitor cells (NPCs) from endogenous neurogenic niches into functional networks thereby supporting stroke recovery. The manner in which microglia contribute towards sculpting neural synapses and networks, both in terms of activity-dependent and homeostatic plasticity, suggests that microglia-mediated pro- and/or anti-inflammatory activity may significantly contribute towards spontaneous neuronal plasticity after ischaemic lesions. In this review, we first introduce some of the key cellular and molecular mechanisms underlying neuroplasticity in stroke and then proceed to discuss the crosstalk between microglia and endogenous neuroplasticity in response to brain ischaemia with special focus on the engagement of synapses and neural networks and their implications for grey matter integrity and function in stroke repair.
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| 19. |
- Sandvig, Ioanna, et al.
(författare)
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RGD-peptide modified alginate by a chemoenzymatic strategy for tissue engineering applications
- 2015
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Ingår i: Journal of Biomedical Materials Research. Part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 103:3, s. 896-906
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Tidskriftsartikel (refereegranskat)abstract
- One of the main challenges in tissue engineering and regenerative medicine is the ability to maintain optimal cell function and survival post-transplantation. Biomaterials such as alginates are commonly used for immunoisolation, while they may also provide structural support to the cell transplants by mimicking the extracellular matrix. In this study, arginine-glycine-aspartate (RGD)-peptide-coupled alginates of tailored composition were produced by adopting a unique chemoenzymatic strategy for substituting the nongelling mannuronic acid on the alginate. Alginates with and without RGD were produced with high and low content of G. Using carbodiimide chemistry 0.1-0.2% of the sugar units were substituted by peptide. Furthermore, the characterization by H-1-nuclear magnetic resonance (NMR) revealed by-products from the coupling reaction that partly could be removed by coal filtration. Olfactory ensheathing cells (OECs) and myoblasts were grown in two-dimensional (2D) and 3D cultures of RGD-peptide modified or unmodified alginates obtained by the chemoenzymatically strategy and compared to native alginate. Both OECs and myoblasts adhered to the RGD-peptide modified alginates in 2D cultures, forming bipolar protrusions. OEC encapsulation resulted in cell survival for up to 9 days, thus demonstrating the potential for short-term 3D culture. Myoblasts showed long-term survival in 3D cultures, that is, up to 41 days post encapsulation. The RGD modifications did not result in marked changes in cell viability in 3D cultures. We demonstrate herein a unique technique for tailoring peptide substituted alginates with a precise and flexible composition, conserving the gel forming properties relevant for the use of alginate in tissue engineering. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 896-906, 2015.
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| 20. |
- Sandvig, Ioanna, et al.
(författare)
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Strategies to Enhance Implantation and Survival of Stem Cells After Their Injection in Ischemic Neural Tissue
- 2017
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert. - 1547-3287 .- 1557-8534. ; 26:8, s. 554-565
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Tidskriftsartikel (refereegranskat)abstract
- High post-transplantation cell mortality is the main limitation of various approaches that are aimed at improving regeneration of injured neural tissue by an injection of neural stem cells (NSCs) and mesenchymal stromal cells (MStroCs) in and/or around the lesion. Therefore, it is of paramount importance to identify efficient ways to increase cell transplant viability. We have previously proposed the "evolutionary stem cell paradigm," which explains the association between stem cell anaerobic/microaerophilic metabolic set-up and stem cell self-renewal and inhibition of differentiation. Applying these principles, we have identified the main critical point in the collection and preparation of these cells for experimental therapy: exposure of the cells to atmospheric O2, that is, to oxygen concentrations that are several times higher than the physiologically relevant ones. In this way, the primitive anaerobic cells become either inactivated or adapted, through commitment and differentiation, to highly aerobic conditions (20%-21% O2 in atmospheric air). This inadvertently compromises the cells' survival once they are transplanted into normal tissue, especially in the hypoxic/anoxic/ischemic environment, which is typical of central nervous system (CNS) lesions. In addition to the findings suggesting that stem cells can shift to glycolysis and can proliferate in anoxia, recent studies also propose that stem cells may be able to proliferate in completely anaerobic or ischemic conditions by relying on anaerobic mitochondrial respiration. In this systematic review, we propose strategies to enhance the survival of NSCs and MStroCs that are implanted in hypoxic/ischemic neural tissue by harnessing their anaerobic nature and maintaining as well as enhancing their anaerobic properties via appropriate ex vivo conditioning.
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| 21. |
- Singh, Gurvinder, et al.
(författare)
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Synthesis of gadolinium oxide nanodisks and gadolinium doped iron oxide nanoparticles for MR contrast agents
- 2017
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry (RSC). - 2050-750X .- 2050-7518. ; 5:3, s. 418-422
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we report the synthesis of differently sized gadolinium oxide nanodisks and gadolinium doped iron oxide spherical and cubic nanoparticles through the thermal decomposition of an oleate precursor. We also demonstrate that these nanoparticles are promising candidates for MR contrast agents.
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| 22. |
- Tukmachev, Dmitry, et al.
(författare)
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Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair
- 2016
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Ingår i: Tissue Engineering. Part A. - : Mary Ann Liebert Inc. - 1937-3341 .- 1937-335X. ; 22:3-4, s. 306-317
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Tidskriftsartikel (refereegranskat)abstract
- Restoration of lost neuronal function after spinal cord injury (SCI) still remains a big challenge for current medicine. One important repair strategy is bridging the SCI lesion with a supportive and stimulatory milieu that would enable axonal rewiring. Injectable extracellular matrix (ECM)-derived hydrogels have been recently reported to have neurotrophic potential in vitro. In this study, we evaluated the presumed neuroregenerative properties of ECM hydrogels in vivo in the acute model of SCI. ECM hydrogels were prepared by decellularization of porcine spinal cord (SC) or porcine urinary bladder (UB), and injected into a spinal cord hemisection cavity. Histological analysis and real-time qPCR were performed at 2, 4, and 8 weeks postinjection. Both types of hydrogels integrated into the lesion and stimulated neovascularization and axonal ingrowth into the lesion. On the other hand, massive infiltration of macrophages into the lesion and rapid hydrogel degradation did not prevent cyst formation, which progressively developed over 8 weeks. No significant differences were found between SC-ECM and UB-ECM. Gene expression analysis revealed significant downregulation of genes related to immune response and inflammation in both hydrogel types at 2 weeks post SCI. A combination of human mesenchymal stem cells with SC-ECM did not further promote ingrowth of axons and blood vessels into the lesion, when compared with the SC-ECM hydrogel alone. In conclusion, both ECM hydrogels bridged the lesion cavity, modulated the innate immune response, and provided the benefit of a stimulatory substrate for in vivo neural tissue regeneration. However, fast hydrogel degradation might be a limiting factor for the use of native ECM hydrogels in the treatment of acute SCI.
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| 23. |
- Valderhaug, Vibeke D., et al.
(författare)
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Early functional changes associated with alpha-synuclein proteinopathy in engineered human neural networks
- 2021
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Ingår i: American Journal of Physiology - Cell Physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 320:6, s. C1141-C1152
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Tidskriftsartikel (refereegranskat)abstract
- A patterned spread of proteinopathy represents a common characteristic of many neurodegenerative diseases. In Parkinson's disease (PD), misfolded forms of α-synuclein proteins accumulate in hallmark pathological inclusions termed Lewy bodies and Lewy neurites. Such protein aggregates seem to affect selectively vulnerable neuronal populations in the substantia nigra and to propagate within interconnected neuronal networks. Research findings suggest that these proteinopathic inclusions are present at very early time points in disease development, even before clear behavioral symptoms of dysfunction arise. In this study, we investigate the early pathophysiology developing after induced formation of such PD-related α-synuclein inclusions in a physiologically relevant in vitro setup using engineered human neural networks. We monitor the neural network activity using multielectrode arrays (MEAs) for a period of 3 wk following proteinopathy induction to identify associated changes in network function, with a special emphasis on the measure of network criticality. Self-organized criticality represents the critical point between resilience against perturbation and adaptational flexibility, which appears to be a functional trait in self-organizing neural networks, both in vitro and in vivo. We show that although developing pathology at early onset is not clearly manifest in standard measurements of network function, it may be discerned by investigating differences in network criticality states.
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| 24. |
- Valderhaug, Vibeke Devold, et al.
(författare)
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Formation of neural networks with structural and functional features consistent with small-world network topology on surface-grafted polymer particles
- 2019
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Ingår i: Royal Society Open Science. - : Royal Society Publishing. - 2054-5703. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- In vitro electrophysiological investigation of neural activity at a network level holds tremendous potential for elucidating underlying features of brain function (and dysfunction). In standard neural network modelling systems, however, the fundamental three-dimensional (3D) character of the brain is a largely disregarded feature. This widely applied neuroscientific strategy affects several aspects of the structure-function relationships of the resulting networks, altering network connectivity and topology, ultimately reducing the translatability of the results obtained. As these model systems increase in popularity, it becomes imperative that they capture, as accurately as possible, fundamental features of neural networks in the brain, such as small-worldness. In this report, we combine in vitro neural cell culture with a biologically compatible scaffolding substrate, surface-grafted polymer particles (PPs), to develop neural networks with 3D topology. Furthermore, we investigate their electrophysiological network activity through the use of 3D multielectrode arrays. The resulting neural network activity shows emergent behaviour consistent with maturing neural networks capable of performing computations, i.e. activity patterns suggestive of both information segregation (desynchronized single spikes and local bursts) and information integration (network spikes). Importantly, we demonstrate that the resulting PP-structured neural networks show both structural and functional features consistent with small-world network topology.
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| 25. |
- Valderhaug, Vibeke Devold, et al.
(författare)
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Micro-and mesoscale aspects of neurodegeneration in engineered human neural networks carrying the LRRK2 G2019S mutation
- 2024
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media S.A.. - 1662-5102. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been widely linked to Parkinson’s disease, where the G2019S variant has been shown to contribute uniquely to both familial and sporadic forms of the disease. LRRK2-related mutations have been extensively studied, yet the wide variety of cellular and network events related to these mutations remain poorly understood. The advancement and availability of tools for neural engineering now enable modeling of selected pathological aspects of neurodegenerative disease in human neural networks in vitro. Our study revealed distinct pathology associated dynamics in engineered human cortical neural networks carrying the LRRK2 G2019S mutation compared to healthy isogenic control neural networks. The neurons carrying the LRRK2 G2019S mutation self-organized into networks with aberrant morphology and mitochondrial dynamics, affecting emerging structure–function relationships both at the micro-and mesoscale. Taken together, the findings of our study points toward an overall heightened metabolic demand in networks carrying the LRRK2 G2019S mutation, as well as a resilience to change in response to perturbation, compared to healthy isogenic controls.
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