Temporal profile of neurogenesis in the subventricular zone, dentate gyrus and cerebral cortex following transient focal cerebral ischemia.
BACKGROUND
In the adult mammalian brain, it is considered that neurogenesis persists in limited regions such as the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ) of the lateral ventricle. On the other hand, neurogenesis in the cortex after cerebral ischemia and its role in post-stroke recovery have not been clarified yet. In this study, we investigated neurogenesis in the cortex and the spatiotemporal profile of neural progenitors in SVZ and DG of rats subjected to transient focal cerebral ischemia.


METHODS
Male Sprague-Dawley rats (270-300 g) were subjected to 60 minute middle cerebral artery occlusion. Proliferating cells were labeled by the cumulative administration of BrdU 1, 2, 3, 4, 6 and 8 weeks after ischemia induction (at weeks 1-4, 6 and 8). Double labeling was also performed with antibodies against BrdU and NeuN.


RESULTS
BrdU-positive cells proliferated in DG and SVZ of the bilateral hemispheres, and their proliferation peaked at week 3 in SVZ and at week 4 in DG. In the peri-infarct zone of cerebral cortex, BrdU-positive cells co-expressed NeuN from weeks 3 to 8.


CONCLUSIONS
Neurogenesis was observed in the cerebral cortex and proliferation of neural progenitors occurred in SVZ and DG of rats subjected to transient focal cerebral ischemia. Our data might indicate that endogenous dormant neural stem cells residing in the cortex were activated by ischemic insult to induce the proliferation of neural progenitors and differentiation into mature neurons.
Kuge
Atsushi
A
Department of Neurosurgery, Faculty of Medicine, Yamagata University, Yamagata, Japan.
Takemura
Sunao
S
Kokubo
Yasuaki
Y
Sato
Shinya
S
Goto
Kaoru
K
Kayama
Takamasa
T
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000503:physiopathology*; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D004268:DNA-Binding Proteins; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013997:Time Factors
D015415:Biomarkers; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D001973:Bromodeoxyuridine