Adult Neural Stem Cells from the Subventricular Zone Give Rise to Reactive Astrocytes in the Cortex after Stroke

Faiz, Maryam; Sachewsky, Nadia; Gascón, Sergio; Bang, K.W. Annie; Morshead, Cindi M.; Nagy, András

doi:10.1016/j.stem.2015.08.002

Cited by 247 publications

(219 citation statements)

References 63 publications

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“…Interestingly, this proliferative population of reactive astrocytes was also shown by clonal analysis to be derived from distinct progenitors 20 , suggesting that one source of reactive astrocyte heterogeneity may be distinct cellular origins. In support of this, neural stem cell (NSC)-derived reactive astrocytes have been shown to contribute to glial scars in the brain 21 , while a recent study found little contribution of NSC-derived reactive astrocytes to SCI-induced glial scars 22 . Therefore, reactive astrocyte heterogeneity is dependent on the site of injury.…”

Section: Functional Diversity Of Glial Cells In the Injured Cnsmentioning

confidence: 99%

The diversity and disparity of the glial scar

2017

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Injury or disease to the CNS results in multifaceted cellular and molecular responses. One such response, the glial scar, is a structural formation of reactive glia around an area of severe tissue damage. While traditionally viewed as a barrier to axon regeneration, beneficial functions of the glial scar have also been recently identified. In this Perspective, we discuss the divergent roles of the glial scar during CNS regeneration and explore the possibility that these disparities are due to functional heterogeneity within the cells of the glial scar—specifically, astrocytes, NG2 glia and microglia.

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Section: Functional Diversity Of Glial Cells In the Injured Cnsmentioning

confidence: 99%

The diversity and disparity of the glial scar

2017

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“…Some reactive astrocytes in peri-infarct areas may arise from the neural stem cells in the subventricular zone. 39 The fact that neural stem cell-derived or immature astrocytes, which express nestin, 33 synthesize less chondroitin sulfate proteoglycans that inhibit axonal growth may support the beneficial effects of peri-infarct astrogliosis in acute ischemic stroke. 21 Moreover, recent evidence suggests that white matter reorganization also participates in poststroke recovery in periinfarct areas.…”

Section: Tachibana Et Al Effects Of Reperfusion In Brain Ischemia 2229mentioning

confidence: 99%

Early Reperfusion After Brain Ischemia Has Beneficial Effects Beyond Rescuing Neurons

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Wakisaka

et al. 2017

Stroke

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Background and Purpose-Recent studies show that successful endovascular thrombectomy 6 to 12 hours after stroke onset enhances functional outcomes 3 months later. In this study, we investigated the effects of reperfusion after ischemia on repair processes in the ischemic areas, as well as on functional recovery, using mouse stroke models. Methods-We examined time-dependent histological changes and functional recovery after transient middle cerebral artery occlusion of different durations, including permanent middle cerebral artery occlusion, using the CB-17 (CB-17/lcr-+/+Jcl) mouse strain, which has poor pial collateral blood flow. Results-Large microtubule-associated protein 2-negative areas of neuronal death were produced in mice subjected to ≥60 minutes of ischemia followed by reperfusion on day 1, while restricted microtubule-associated protein 2-negative regions were observed in mice subjected to a 45-minute period of ischemia. A substantial reduction in microtubule-associated protein 2-negative areas was observed on day 7 in mice given early reperfusion and was associated with better functional recovery. Klüver-Barrera staining demonstrated that white matter injury on day 1 was significantly lesser in mice with reperfusion. Immunohistochemistry and electron microscopy revealed that a greater number of endothelial cells were present in the infarct areas in mice with earlier reperfusion and were associated with a more rapid recruitment of plateletderived growth factor receptor β-positive pericytes and subsequent intrainfarct fibrosis. Early reperfusion also resulted in a greater accumulation of glial fibrillary acidic protein-positive astrocytes in peri-infarct areas. Peri-infarct astrogliosis was attenuated in platelet-derived growth factor receptor β heterozygous knockout mice. Conclusions-Early reperfusion after ischemia enhances the survival of endothelial cells and pericytes within ischemic areas even after the infarct is established, resulting in efficient intrainfarct fibrosis and peri-infarct astrogliosis. These effects might be associated with efficient peri-infarct reorganization and functional recovery. in peri-infarct areas in experimental researches, although this remains controversial. 21,22 Furthermore, it is experimentally suggested that efficient fibrotic formation within areas of infarct may promote peri-infarct astrogliosis. 23 Thus, if these repair processes are associated with functional recovery, apparent infarct volumes at early phases may not be suitable for predicting functional outcome.To date, few papers have focused on the effects of reperfusion on poststroke repair processes in both animals and human. In the present study, we hypothesized that early reperfusion might elicit efficient tissue repair, such as intrainfarct fibrosis and peri-infarct astrogliosis, and lead to functional recovery even if it does not prevent neuronal death within the ischemic areas. To examine the precise effects of ischemia-reperfusion in the MCA, we performed tMCAO of various durations, as well as perm...

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“…This age effect on OPC and white matter responses appears to be mediated by greater local inflammation in the aged brain81 and by intrinsic differences in aged OPCs 82. In another aspect of gliogenesis, stroke induces proliferation of astrocytes adjacent to the lesion,83, 84 and a remarkable generation of new astrocytes from neural progenitor cells that migrate from the subventricular zone 85, 86. Astrocytes proliferate near human stroke,87 but the role of this generation of new astrocytes immediately adjacent to stroke in recovery remains to be defined.…”

Section: The Brain Forms Regenerative Cellular Niches During Repair Amentioning

confidence: 99%

Emergent properties of neural repair: elemental biology to therapeutic concepts

Carmichael

2016

Annals of Neurology

121

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Stroke is the leading cause of adult disability. The past decade has seen advances in basic science research of neural repair in stroke. The brain forms new connections after stroke, which have a causal role in recovery of function. Brain progenitors, including neuronal and glial progenitors, respond to stroke and initiate a partial formation of new neurons and glial cells. The molecular systems that underlie axonal sprouting, neurogenesis, and gliogenesis after stroke have recently been identified. Importantly, tractable drug targets exist within these molecular systems that might stimulate tissue repair. These basic science advances have taken the field to its first scientific milestone; the elemental principles of neural repair in stroke have been identified. The next stages in this field involve understanding how these elemental principles of recovery interact in the dynamic cellular systems of the repairing brain. Emergent principles arise out of the interaction of the fundamental or elemental principles in a system. In neural repair, the elemental principles of brain reorganization after stroke interact to generate higher order and distinct concepts of regenerative brain niches in cellular repair, neuronal networks in synaptic plasticity, and the distinction of molecular systems of neuroregeneration. Many of these emergent principles directly guide the development of new therapies, such as the necessity for spatial and temporal control in neural repair therapy delivery and the overlap of cancer and neural repair mechanisms. This review discusses the emergent principles of neural repair in stroke as they relate to scientific and therapeutic concepts in this field. Ann Neurol 2016;79:895–906

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Adult Neural Stem Cells from the Subventricular Zone Give Rise to Reactive Astrocytes in the Cortex after Stroke

Cited by 247 publications

References 63 publications

The diversity and disparity of the glial scar

The diversity and disparity of the glial scar

Early Reperfusion After Brain Ischemia Has Beneficial Effects Beyond Rescuing Neurons

Emergent properties of neural repair: elemental biology to therapeutic concepts

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