Astrocyte failure as a cause of CNS dysfunction

Sofroniew, Michael V.

doi:10.1038/sj.mp.4000753

Cited by 44 publications

(31 citation statements)

References 35 publications

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“…In addition to a potential role of oligodendrocyte differentiation in supporting recovery after primate SCI, astrocytic differentiation observed in this study could also contribute to recovery. Immature astrocytes facilitate axon outgrowth (Smith et al, 1990) and recovery of the CNS from injury requires astrocyte activation (Sofroniew, 2000;Faulkner et al, 2004;Smith et al, 1990). In agreement with the present findings, a previous study also reported extensive glial differentiation (Zai and Wrathall, 2005) of newly born cells after contusive SCI in rats.…”

Section: Discussionsupporting

confidence: 81%

“…There are two long-term consequences of this spontaneous cell division: (1) a subpopulation of newly dividing cells adopt mature oligodendrocyte markers in regions of demyelination, appearing to ensheath or remyelinate axons, and (2) new astrocytes are generated, a phenomenon that is likely to be important for reestablishing parenchymal stability and the blood-brain barrier after injury (Sofroniew, 2000;Faulkner et al, 2004). Of note, primate SCI does not result in new neuron formation derived from cells dividing within 5 d of injury.…”

Section: Discussionmentioning

confidence: 99%

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Endogenous Neurogenesis Replaces Oligodendrocytes and Astrocytes after Primate Spinal Cord Injury

Yang¹,

Lu²,

McKay³

et al. 2006

J. Neurosci.

146

123

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Neurogenesis has been described in various regions of the CNS throughout life. We examined the extent of natural cell division and replacement from 7 weeks to 7 months after cervical spinal cord injury in four adult rhesus monkeys. Bromodeoxyuridine (BrdU) injections revealed an increase of Ͼ80-fold in the number of newly divided cells in the primate spinal cord after injury, with an average of 725,000 BrdU-labeled cells identified per monkey in the immediate injury zone. By 7 months after injury, 15% of these new cells expressed mature markers of oligodendrocytes and 12% expressed mature astrocytic markers. Newly born oligodendrocytes were present in zones of injury-induced demyelination and appeared to ensheath or remyelinate host axons. Thus, cell replacement is an extensive natural compensatory response to injury in the primate spinal cord that contributes to neural repair and is a potential target for therapeutic enhancement.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Endogenous Neurogenesis Replaces Oligodendrocytes and Astrocytes after Primate Spinal Cord Injury

Yang¹,

Lu²,

McKay³

et al. 2006

J. Neurosci.

146

123

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“…CNTF was chosen in this study because of its ability to enhance astrocytic differentiation Lillien et al 1988;Johe et al 1996;Bonni et al 1997;Koblar et al 1998;Rajan and McKay 1998;Whittemore et al 1999). Astrocytes regulate the immune response and blood-brain barrier, promote oligodendrocyte remyelination, influence the localized metabolism of glutamate (thereby reducing glutamate toxicity and secondary injury), and provide trophic support for surviving neurons (reviewed in Sofroniew 2000). Astrocytes aid remyelination by releasing leukemia inhibitory factor, which stimulates myelination by oligodendrocytes (Ishibashi et al 2006).…”

Section: Generation Of Enhanced Populations Of Differentiated Progenymentioning

confidence: 99%

Region-specific Differentiation Potential of Adult Rat Spinal Cord Neural Stem/Precursors and Their Plasticity in Response to In Vitro Manipulation

Kulbatski

Tator

2009

J Histochem Cytochem.

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S U M M A R Y This study characterized the differentiation of neural stem/precursor cells (NSPCs) isolated from different levels of the spinal cord (cervical vs lumbar cord) and different regions along the neuraxis (brain vs cervical spinal cord) of adult male Wistar enhanced green fluorescent protein rats. The differentiation of cervical spinal cord NSPCs was further examined after variation of time in culture, addition of growth factors, and changes in cell matrix and serum concentration. Brain NSPCs did not differ from cervical cord NSPCs in the percentages of neurons, astrocytes, or oligodendrocytes but produced 26.9% less radial glia. Lumbar cord NSPCs produced 30.8% fewer radial glia and 6.9% more neurons compared with cervical cord NSPCs. Spinal cord NSPC differentiation was amenable to manipulation by growth factors and changes in in vitro conditions. This is the first study to directly compare the effect of growth factors, culturing time, serum concentration, and cell matrix on rat spinal cord NSPCs isolated, propagated, and differentiated under identical conditions. (J Histochem Cytochem 57:405-423, 2009)

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“…Thus, high concentrations of axon growth-inhibitory chondroitin sulfate proteoglycans (CSPG), mainly produced by reactive astrocytes, are found in the scar tissue, which is at the same time characterized by breakdown of the blood-brain barrier (BBB). [1][2][3][4][5] CSPG, as well as heparan sulfate proteoglycans (HSPG), are also found in the basement membrane (BM) of blood vessels. 6,7 Moreover, secondary injuries and chronic functional deficits after SCI are associated with alterations of the microvasculature, 8 including increased BBB permeability, 9 modified vascular morphology, [10][11][12] and BM duplication.…”

mentioning

confidence: 99%

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

Milbreta

Boxberg

Mailly

et al. 2014

Journal of Neurotrauma

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Upregulation of extracellular chondroitin sulfate proteoglycans (CSPG) is a primary cause for the failure of axons to regenerate after spinal cord injury (SCI), and the beneficial effect of their degradation by chondroitinase ABC (ChABC) is widely documented. Little is known, however, about the effect of ChABC treatment on astrogliosis and revascularization, two important factors influencing axon regrowth. This was investigated in the present study. Immediately after a spinal cord hemisection at thoracic level 8-9, we injected ChABC intrathecally at the sacral level, repeated three times until 10 days post-injury. Our results show an effective cleavage of CSPG glycosaminoglycan chains and stimulation of axonal remodeling within the injury site, accompanied by an extended period of astrocyte remodeling (up to 4 weeks). Interestingly, ChABC treatment favored an orientation of astrocytic processes directed toward the injury, in close association with axons at the lesion entry zone, suggesting a correlation between axon and astrocyte remodeling. Further, during the first weeks post-injury, ChABC treatment affected the morphology of laminin-positive blood vessel basement membranes and vessel-independent laminin deposits: hypertrophied blood vessels with detached or duplicated basement membrane were more numerous than in lesioned untreated animals. In contrast, at later time points, laminin expression increased and became more directly associated with newly formed blood vessels, the size of which tended to be closer to that found in intact tissue. Our data reinforce the idea that ChABC injection in combination with other synergistic treatments is a promising therapeutic strategy for SCI repair.

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Astrocyte failure as a cause of CNS dysfunction

Cited by 44 publications

References 35 publications

Endogenous Neurogenesis Replaces Oligodendrocytes and Astrocytes after Primate Spinal Cord Injury

Endogenous Neurogenesis Replaces Oligodendrocytes and Astrocytes after Primate Spinal Cord Injury

Region-specific Differentiation Potential of Adult Rat Spinal Cord Neural Stem/Precursors and Their Plasticity in Response to In Vitro Manipulation

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

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