Increased proliferation of neural progenitor cells but reduced survival of newborn cells in the contralateral hippocampus after focal cerebral ischemia in rats

Ken Ichiro Takasawa, Kazuo Kitagawa, Yoshiki Yagita, Tsutomu Sasaki, Shigeru Tanaka, Kohji Matsushita, Toshiho Ohstuki, Takaki Miyata, Hideyuki Okano, Masatsugu Hori, Masayasu Matsumoto

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Recent studies demonstrated that neurogenesis in the adult hippocampus increased after transient global ischemia; however, the molecular mechanism underlying increased neurogenesis after ischemia remains unclear. The finding that proliferation of progenitor cells occurred at least a week after ischemic insult suggests that the stimulus was not an ischemic insult to progenitor cells. To clarify whether focal ischemia increases the rate of neurogenesis in the remote area, the authors examined the contralateral hemisphere in rats subjected to permanent occlusion of the middle cerebral artery. In the subgranular zone of the hippocampal dentate gyrus, the numbers of bromodeoxyuridine (BrdU)-positive cells increased approximately sixfold 7 days after ischemia. In double immunofluorescence staining, more than 80% of newborn cells expressed Musashil, a marker of neural stem/progenitor cells, but only approximately 10% of BrdU-positive cells expressed glial fibrillary acidic protein (GFAP), a marker of astrocytes. The number of BrdU-positive cells markedly decreased 28 days after BrdU administration after ischemia, but it was still elevated compared with that of sham-operated rats. In double immunofluorescence staining, 80% of newborn cells expressed NeuN, a marker of differentiated neurons, and 10% of BrdU-positive cells expressed GFAP. However, in the other areas of the contralateral hemisphere including the rostral subventricular zone, the number of BrdU-positive cells remained unchanged. These results showed that focal ischemia stimulated the proliferation of neuronal progenitor cells, but did not support survival of newborn cells in the contralateral hippocampus.

Original languageEnglish
Pages (from-to)299-307
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume22
Issue number3
DOIs
Publication statusPublished - 2002 Jan 1
Externally publishedYes

Keywords

  • Hippocampus
  • Ischemia
  • Musashi-1 (Msi1)
  • Neurogenesis
  • Neuronal progenitor cells

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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