| 1. |
|
|
| 2. |
- Aldskogius, Håkan, et al.
(författare)
-
Central neuron-glial and glial-glial interactions following axon injury
- 1998
-
Ingår i: Progress in Neurobiology. - 0301-0082 .- 1873-5118. ; 55:1, s. 1-26
-
Tidskriftsartikel (refereegranskat)abstract
- Axon injury rapidly activates microglial and astroglial cells close to the axotomized neurons. Following motor axon injury, astrocytes upregulate within hour(s) the gap junction protein connexin-43, and within one day glial fibrillary acidic protein (GFAP). Concomitantly, microglial cells proliferate and migrate towards the axotomized neuron perikarya. Analogous responses occur in central termination territories of peripherally injured sensory ganglion cells. The activated microglia express a number of inflammatory and immune mediators. When neuron degeneration occurs, microglia act as phagocytes. This is uncommon after peripheral nerve injury in the adult mammal, however, and the functional implications of the glial cell responses in this situation are unclear. When central axons are injured, the glial cell responses around the affected neuron perikarya appears to be minimal or absent, unless neuron degeneration occurs. Microglia proliferate, and astrocytes upregulate GFAP along central axons undergoing anterograde, Wallerian, degeneration. Although microglia develop into phagocytes, they eliminate the disintegrating myelin very slowly, presumably because they fail to release molecules which facilitate phagocytosis. During later stages of Wallerian degeneration, oligodendrocytes express clusterin, a glycoprotein implicated in several conditions of cell degeneration. A hypothetical scheme for glial cell activation following axon injury is discussed, implying the injured neurons initially interact with adjacent astrocytes. Subsequently, neighbouring resting microglia are activated. These glial reactions are amplified by paracrine and autocrine mechanisms, in which cytokines appear to be important mediators. The specific functional properties of the activated glial cells will determine their influence on neuronal survival, axon regeneration, and synaptic plasticity. The control of the induction and progression of these responses are therefore likely to be critical for the outcome of, for example, neurotrauma, brain ischemia and chronic neurodegenerative diseases.
|
|
| 3. |
- Aldskogius, Håkan, 1943-, et al.
(författare)
-
Dorsal Root Injury : A Model for Exploring Pathophysiology and Therapeutic Strategies in Spinal Cord Injury
- 2021
-
Ingår i: Cells. - : MDPI. - 2073-4409. ; 10:9
-
Forskningsöversikt (refereegranskat)abstract
- Unraveling the cellular and molecular mechanisms of spinal cord injury is fundamental for our possibility to develop successful therapeutic approaches. These approaches need to address the issues of the emergence of a non-permissive environment for axonal growth in the spinal cord, in combination with a failure of injured neurons to mount an effective regeneration program. Experimental in vivo models are of critical importance for exploring the potential clinical relevance of mechanistic findings and therapeutic innovations. However, the highly complex organization of the spinal cord, comprising multiple types of neurons, which form local neural networks, as well as short and long-ranging ascending or descending pathways, complicates detailed dissection of mechanistic processes, as well as identification/verification of therapeutic targets. Inducing different types of dorsal root injury at specific proximo-distal locations provide opportunities to distinguish key components underlying spinal cord regeneration failure. Crushing or cutting the dorsal root allows detailed analysis of the regeneration program of the sensory neurons, as well as of the glial response at the dorsal root-spinal cord interface without direct trauma to the spinal cord. At the same time, a lesion at this interface creates a localized injury of the spinal cord itself, but with an initial neuronal injury affecting only the axons of dorsal root ganglion neurons, and still a glial cell response closely resembling the one seen after direct spinal cord injury. In this review, we provide examples of previous research on dorsal root injury models and how these models can help future exploration of mechanisms and potential therapies for spinal cord injury repair.
|
|
| 4. |
- Aldskogius, Håkan, et al.
(författare)
-
Microglia and Neuropathic Pain
- 2013
-
Ingår i: CNS & Neurological Disorders. - : Wiley. - 1871-5273 .- 1996-3181. ; 12:6, s. 768-772
-
Tidskriftsartikel (refereegranskat)abstract
- Neuropathic pain is a serious consequence of injury or disease in the nervous system itself. Current treatment options for this condition are often unsatisfactory. From being originally viewed as a diseased caused by neuronal dysfunction, a growing body of evidence implicate activated microglia as a key player in the development of this pain condition. In this review, some of the evidence for this proposal is briefly discussed and placed in a translational context, pointing out the difficulties in translating commonly used animal models of neuropathic pain to the clinical condition, as well as emphasizing the broader role of activated microglia in the injured or diseased nervous system.
|
|
| 5. |
- Aldskogius, Håkan, et al.
(författare)
-
Strategies for repair of the deafferented spinal cord
- 2002
-
Ingår i: Brain Research Reviews. - 0165-0173 .- 1872-6321. ; 40:1-3, s. 301-308
-
Tidskriftsartikel (refereegranskat)abstract
- Deafferentation of the spinal cord by interruption of the sensory fibers in the dorsal roots highlights the problem of regeneration failure in the central nervous system. The injured dorsal root axons regenerate steadily, albeit slowly, in the peripheral compartment of the dorsal root, but abruptly cease to elongate when confronted with the interface between the peripheral and central nervous system, the dorsal root transitional zone (DRTZ). The glial cells of the CNS and their products together form this regeneration barrier. Recent years have witnessed several successful approaches to, at least in part, overcome this barrier. Particularly promising results have been obtained by (1). the replacement of adult non-regenerating dorsal root ganglion neurons with corresponding cells from embryonic or fetal donors, (2). the implantation of olfactory ensheathing cells at the DRTZ, and (3). immediate intrathecal infusion of growth factors to which dorsal root ganglion cells respond. In all these instances, growth of sensory axons into the adult spinal cord, as well as return of spinal cord connectivity, have been demonstrated. These findings suggest routes towards treatment strategies for plexus avulsion, and contribute to our understanding of possibilities to overcome regeneration failure in the spinal cord.
|
|
| 6. |
- Brännvall, Karin, et al.
(författare)
-
Central nervous system stem/progenitor cells form neurons and peripheral glia after transplantation to the dorsal root ganglion.
- 2006
-
Ingår i: NeuroReport. - 0959-4965 .- 1473-558X. ; 17:6, s. 623-628
-
Tidskriftsartikel (refereegranskat)abstract
- We asked whether neural stem/progenitor cells from the cerebral cortex of E14.5 enhanced green fluorescent protein transgenic mice are able to survive grafting and differentiate in the adult rat dorsal root ganglion. Neurospheres were placed in lumbar dorsal root ganglion cavities after removal of the dorsal root ganglia. Alternatively, dissociated neurospheres were injected into intact dorsal root ganglia. Enhanced green fluorescent protein-positive cells in the dorsal root ganglion cavity were located in clusters and expressed beta-III-tubulin or glial fibrillary acidic protein after 1 month, whereas after 3 months, surviving grafted cells expressed only glial fibrillary acidic protein. In the intact adult DRG, transplanted neural stem/progenitor cells surrounded dorsal root ganglion cells and fibers, and expressed glial but not neuronal markers. These findings show that central nervous system stem/progenitor cells can survive and differentiate into neurons and peripheral glia after xenotransplantation to the adult dorsal root ganglion.
|
|
| 7. |
- Garcia-Bennett, Alfonso E., et al.
(författare)
-
Delivery of Differentiation Factors by Mesoporous Silica Particles Assists Advanced Differentiation of Transplanted Murine Embryonic Stem Cells
- 2013
-
Ingår i: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 2:11, s. 906-915
-
Tidskriftsartikel (refereegranskat)abstract
- Stem cell transplantation holds great hope for the replacement of damaged cells in the nervous system. However, poor long-term survival after transplantation and insufficiently robust differentiation of stem cells into specialized cell types in vivo remain major obstacles for clinical application. Here, we report the development of a novel technological approach for the local delivery of exogenous trophic factor mimetics to transplanted cells using specifically designed silica nanoporous particles. We demonstrated that delivering Cintrofin and Gliafin, established peptide mimetics of the ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, respectively, with these particles enabled not only robust functional differentiation of motor neurons from transplanted embryonic stem cells but also their long-term survival in vivo. We propose that the delivery of growth factors by mesoporous nanoparticles is a potentially versatile and widely applicable strategy for efficient differentiation and functional integration of stem cell derivatives upon transplantation.
|
|
| 8. |
- Garcia-Bennett, Alfonso E., et al.
(författare)
-
In vitro generation of motor neuron precursors from mouse embryonic stem cells using mesoporous nanoparticles
- 2014
-
Ingår i: Nanomedicine. - 1743-5889 .- 1748-6963. ; 9:16, s. 2457-2466
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Stem cell-derived motor neurons (MNs) are utilized to develop replacement strategies for spinal cord disorders. Differentiation of embryonic stem cells into MN precursors involves factors and their repeated administration. We investigated if delivery of factors loaded into mesoporous nanoparticles could be effective for stem cell differentiation in vitro. Materials & methods: We used a mouse embryonic stem cell line expressing green fluorescent protein under the promoter for the MN-specific gene Hb9 to visualize the level of MN differentiation. The differentiation of stem cells was evaluated by expression of MN-specific transcription factors monitored by quantitative real-time PCR reactions and immunocytochemistry. Results: Mesoporous nanoparticles have strong affiliation to the embryoid bodies, penetrate inside the embryoid bodies and come in contact with differentiating cells. Conclusion: Repeated administration of soluble factors into a culture medium can be avoided due to a sustained release effect using mesoporous silica.
|
|
| 9. |
- Goursaud, Stephanie, et al.
(författare)
-
Cultured astrocytes derived from corpus callosum or cortical grey matter show distinct glutamate handling properties
- 2009
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 108:6, s. 1442-1452
-
Tidskriftsartikel (refereegranskat)abstract
- While the astrocytic control of extracellular glutamate concentration at synaptic contacts is well characterized, little is known regarding the clearance of glutamate along axon tracts, even though local excitotoxic damage has been reported. Therefore, we have compared glutamate handling in astrocyte cultures derived from white matter (corpus callosum) and grey matter tissues (cortical structures). These populations of astrocytes showed clearly distinct phenotypes, adopting stellate or protoplasmic morphologies respectively. In addition, white matter astrocytes showed high densities of the intermediate filament proteins glial fibrillary acidic protein, vimentin and nestin. The glutamate-aspartate transporter and glutamate transporter-1, as well as glutamine synthetase, were found to be expressed at higher levels in white matter compared with grey matter astrocytes. Consistent with this aspartate uptake capacity was three to fourfold higher in white matter cells, and the use of specific inhibitors revealed a substantial activity of glutamate transporter-1, contrasting with grey matter cells where this transporter appeared poorly functional. In addition, expression of type 5 metabotropic glutamate receptors was considerably higher in white matter astrocytes where the agonist (S)-3,5-dihydroxyphenylglycine triggered a large release of intracellular calcium. Differences in these astrocyte cultures were also observed when exposed to experimental conditions that trigger glial activation. This study highlights typical features of cultured astrocytes derived from white matter tissues, which appear constitutively adapted to handle excitotoxic insults. Moreover, the expression and activity of the astroglial components involved in the control of glutamatergic transmission are reinforced when these cells are maintained under conditions mimicking a gliotic environment.
|
|
| 10. |
- Grouwels, G., et al.
(författare)
-
Differentiating neural crest stem cells induce proliferation of cultured rodent islet beta cells
- 2012
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 55:7, s. 2016-2025
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesisEfficient stimulation of cycling activity in cultured beta cells would allow the design of new strategies for cell therapy in diabetes. Neural crest stem cells (NCSCs) play a role in beta cell development and maturation and increase the beta cell number in co-transplants. The mechanism behind NCSC-induced beta cell proliferation and the functional capacity of the new beta cells is not known.MethodsWe developed a new in vitro co-culture system that enables the dissection of the elements that control the cellular interactions that lead to NCSC-dependent increase in islet beta cells.ResultsMouse NCSCs were cultured in vitro, first in medium that stimulated their proliferation, then under conditions that supported their differentiation. When mouse islet cells were cultured together with the NCSCs, more than 35% of the beta cells showed cycle activity. This labelling index is more than tenfold higher than control islets cultured without NCSCs. Beta cells that proliferated under these culture conditions were fully glucose responsive in terms of insulin secretion. NCSCs also induced beta cell proliferation in islets isolated from 1-year-old mice, but not in dissociated islet cells isolated from human donor pancreas tissue. To stimulate beta cell proliferation, NCSCs need to be in intimate contact with the beta cells.Conclusions/interpretationCulture of islet cells in contact with NCSCs induces highly efficient beta cell proliferation. The reported culture system is an excellent platform for further dissection of the minimal set of factors needed to drive this process and explore its potential for translation to diabetes therapy.
|
|
