Cell cycle protein expression in proliferating microglia and astrocytes following transient global cerebral ischemia in the rat

Hiroyuki Kato, Akira Takahashi, Yasuto Itoyama

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)

Abstract

Cerebral ischemia induces microglial and astroglial activation, which may play a crucial role in the development of ischemic neuronal damage. In this study, we examined the role of cell cycle proteins in glial proliferation in the hippocampus following 10min of global cerebral ischemia in the rat. Proliferating cells were identified with immunostaining for proliferating cell nuclear antigen (PCNA), and glial cells were visualized with immunostaining for microglial response factor-1 (microglia/macrophages) and glial fibrillary acidic protein (astrocytes). Expression of cyclin D1 and cyclin-dependent kinase-4 was also examined with double label immunohistochemistry. Proliferating cells in the CA1 region after ischemia consisted of microglia and much fewer astrocytes. Microglial activation and proliferation (7.6-fold increase in number after 7 days) were preceded by an increase in PCNA-positive microglia; 83% of microglia were PCNA-positive after 2 days. Astrocytes increased by 1.8-fold after 7 days, and only 6% of astrocytes became PCNA-positive by day 7. Cyclin D1 and cyclin-dependent kinase-4 immunoreactivity appeared in these glial cells in parallel with the expression of PCNA. The findings suggest that the accumulation of brain macrophages elicited by transient cerebral ischemia is caused predominantly by activation and proliferation of resident microglia through the upregulation of cell cycle proteins.

Original languageEnglish
Pages (from-to)215-221
Number of pages7
JournalBrain Research Bulletin
Volume60
Issue number3
DOIs
Publication statusPublished - 2003 May 15

Keywords

  • Astrocytes
  • Cell cycle protein
  • Cerebral ischemia
  • Hippocampus
  • Microglia
  • Proliferation

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Cell cycle protein expression in proliferating microglia and astrocytes following transient global cerebral ischemia in the rat'. Together they form a unique fingerprint.

Cite this