Evidence for stroke-induced neurogenesis in the human brain

Jin, Kunlin; Wang, Xiaomei; Xie, Lin; Mao, Xiao Ou; Zhu, Wei; Wang, Yin; Shen, Jianfeng; Mao, Ying; Banwait, Surita; Greenberg, David A.

doi:10.1073/pnas.0603512103

Cited by 552 publications

(364 citation statements)

References 20 publications

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“…Enhanced neurogenesis has been suggested to occur in stroke patients (Jin et al, 2006, Macas et al, 2006. The notion that enhanced proliferation of NSPCs following stroke promotes functional recovery (Nygren et al, 2006, Thored et al, 2006) makes these findings potentially clinically relevant.…”

Section: Discussionmentioning

confidence: 97%

Brain injury activates microglia that induce neural stem cell proliferation ex vivo and promote differentiation of neurosphere-derived cells into neurons and oligodendrocytes

et al. 2010

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Here, we developed an ex vivo method to investigate how the proliferation of NSPCs changes over time after experimental stroke or excitotoxic striatal lesion in the adult rat brain by studying the effects of microglial cells derived from an injured brain on NSPCs. We isolated NSPCs from the SVZ of brains with lesions and analyzed their growth and differentiation when cultured as neurospheres. We found that NSPCs isolated from the brains 1-2 weeks following injury consistently generated more and larger neurospheres than those harvested from naïve brains. We attributed these effects to the presence of microglial cells in NSPC cultures that originated from injured brains. We suggest that the effects are due to released factors because we observed increased proliferation of NSPCs isolated from non-injured brains when they were exposed to conditioned medium from cultures containing microglial cells derived from injured brains. Furthermore, we found that NSPCs derived from injured brains were more likely to differentiate into neurons and oligodendrocytes than astrocytes. Our ex vivo system reliably mimics what is observed in vivo following brain injury. It constitutes a powerful tool that could be used to identify factors that promote NSPC proliferation and differentiation in response to injury-induced activation of microglial cells, by using tools such as proteomics and gene array technology.4

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Section: Discussionmentioning

confidence: 97%

Brain injury activates microglia that induce neural stem cell proliferation ex vivo and promote differentiation of neurosphere-derived cells into neurons and oligodendrocytes

et al. 2010

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“…However, despite a robust initial neurogenic response, most of these immature neurons die. Poststroke neurogenesis has been reported in human stroke, by utilizing tissue staining for protein markers of immature neurons in autopsy material 72, 73, 74. However, a lack of poststroke neurogenesis has been reported in human cortical stroke, using 14 C labeling of newly born cells 75.…”

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

113

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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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“…In humans, there is also evidence for enhanced SVZ cell proliferation and neuroblast formation after stroke (Jin et al, 2006;Marti-Fabregas et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Meteorin is a Chemokinetic Factor in Neuroblast Migration and Promotes Stroke-Induced Striatal Neurogenesis

Wang

Andrade

Torp

et al. 2011

J Cereb Blood Flow Metab

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Ischemic stroke affecting the adult brain causes increased progenitor proliferation in the subventricular zone (SVZ) and generation of neuroblasts, which migrate into the damaged striatum and differentiate to mature neurons. Meteorin (METRN), a newly discovered neurotrophic factor, is highly expressed in neural progenitor cells and immature neurons during development, suggesting that it may be involved in neurogenesis. Here, we show that METRN promotes migration of neuroblasts from SVZ explants of postnatal rats and stroke-subjected adult rats via a chemokinetic mechanism, and reduces N-methyl-D-asparate-induced apoptotic cell death in SVZ cells in vitro. Stroke induced by middle cerebral artery occlusion upregulates the expression of endogenous METRN in cells with neuronal phenotype in striatum. Recombinant METRN infused into the stroke-damaged brain stimulates cell proliferation in SVZ, promotes neuroblast migration, and increases the number of immature and mature neurons in the ischemic striatum. Our findings identify METRN as a new factor promoting neurogenesis both in vitro and in vivo by multiple mechanisms. Further work will be needed to translate METRN's actions on endogenous neurogenesis into improved recovery after stroke.

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Evidence for stroke-induced neurogenesis in the human brain

Cited by 552 publications

References 20 publications

Brain injury activates microglia that induce neural stem cell proliferation ex vivo and promote differentiation of neurosphere-derived cells into neurons and oligodendrocytes

Brain injury activates microglia that induce neural stem cell proliferation ex vivo and promote differentiation of neurosphere-derived cells into neurons and oligodendrocytes

Emergent properties of neural repair: elemental biology to therapeutic concepts

Meteorin is a Chemokinetic Factor in Neuroblast Migration and Promotes Stroke-Induced Striatal Neurogenesis

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