Brain self-protection: The role of endogenous neural progenitor cells in adult brain after cerebral cortical ischemia

Bin Li, Chun Shu Piao, Xiao Yun Liu, Wen Ping Guo, Yue Qiang Xue, Wei Ming Duan, Maria E. Gonzalez-Toledo, Li Ru Zhao*

*Corresponding author for this work

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Convincing evidence has shown that brain ischemia causes the proliferation of neural stem cells/neural progenitor cells (NSCs/NPCs) in both the subventricular zone (SVZ) and the subgranular zone (SGZ) of adult brain. The role of brain ischemia-induced NSC/NPC proliferation, however, has remained unclear. Here we have determined whether brain ischemia-induced amplification of the NSCs/NPCs in adult brain is required for brain self-protection. The approach of intracerebroventricular (ICV) infusion of cytosine arabinoside (Ara-C), an inhibitor for cell proliferation, for the first 7 days after brain ischemia was used to block ischemia-induced NSC/NPC proliferation. We observed that ICV infusion of Ara-C caused a complete blockade of NSC/NPC proliferation in the SVZ and a dramatic reduction of NSC/NPC proliferation in the SGZ. Additionally, as a result of the inhibition of ischemia-induced NSC/NPC pool amplification, the number of neurons in the hippocampal CA1 and CA3 was significantly reduced, the infarction size was significantly enlarged, and neurological deficits were significantly worsened after focal brain ischemia. We also found that an NSC/NPC-conditioned medium showed neuroprotective effects in vitro and that adult NSC/NPC-released brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) are required for NSC/NPC-conditioned medium-induced neuroprotection. These data suggest that NSC/NPC-generated trophic factors are neuroprotective and that brain ischemia-triggered NSC/NPC proliferation is crucial for brain protection. This study provides insights into the contribution of endogenous NSCs/NPCs to brain self-protection in adult brain after ischemia injury.

Original languageEnglish (US)
Pages (from-to)91-102
Number of pages12
JournalBrain research
Volume1327
DOIs
StatePublished - Apr 23 2010

Keywords

  • Neural progenitor cell
  • Neural stem cell
  • Neuroprotection
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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    Li, B., Piao, C. S., Liu, X. Y., Guo, W. P., Xue, Y. Q., Duan, W. M., Gonzalez-Toledo, M. E., & Zhao, L. R. (2010). Brain self-protection: The role of endogenous neural progenitor cells in adult brain after cerebral cortical ischemia. Brain research, 1327, 91-102. https://doi.org/10.1016/j.brainres.2010.02.030