Brain self-protection: the role of endogenous neural progenitor cells in adult brain after cerebral cortical ischemia.
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 7days 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.
Li
Bin
B
Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
Piao
Chun-Shu
CS
Liu
Xiao-Yun
XY
Guo
Wen-Ping
WP
Xue
Yue-Qiang
YQ
Duan
Wei-Ming
WM
Gonzalez-Toledo
Maria E
ME
Zhao
Li-Ru
LR
D053687:Adult Stem Cells / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020287:In Situ Nick-End Labeling / Q000379:methods; D020547:Lateral Ventricles / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009460:Neurologic Examination / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D055748:SOXB1 Transcription Factors / Q000378:metabolism
D017077:Culture Media, Conditioned; D007166:Immunosuppressive Agents; D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D003561:Cytarabine; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine