Long-term time course of regional changes in cholinergic indices following transient ischemia in the spontaneously hypertensive rat brain

Norio Ogawa, Masato Asanuma, Ken Ichi Tanaka, Hiroshi Hirata, Yoichi Kondo, Masaki Goto, Masamitsu Kawauchi, Toshio Ogura

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Using an animal model of forebrain ischemia in spontaneously hypertensive rats (SHR) by 3-h bilateral carotid occlusion, and various indices of the cerebral cholinergic system were assessed for periods up to 24 weeks. The lesions observed histologically in the hippocampus of SHR 2 weeks after ischemia were less severe than those in the frontal cortex. Marked elevation of acetylcholine concentration was transiently observed in the frontal cortex, hippocampus and thalamus + midbrain at 2 weeks, and in the striatum at 1-4 weeks after ischemia. Choline acetyltransferase activity remained unchanged in all regions throughout the experimental period except for a minimal decrease in the frontal cortex at 4 weeks. Choline esterase (ChE) activity was slightly decreased in the frontal cortex at 2-4 weeks after ischemia but recovered by 8 weeks. A decrease in the hippocampus was seen at 8 weeks. The B(max) for the M1-receptor was significantly reduced by 2 weeks in the frontal cortex and by 4 weeks in the hippocampus. Low B(max) values in both regions persisted through week 24. These delayed hippocampal changes in the ChE activity and M1-receptor in SHR were similar to those of the very much delayed changes in M1-receptor previously reported in the gerbil model for transient ischemia. In contrast, Wistar-Kyoto rats (WKY), used as normotensive controls, exhibited no histological or biochemical changes for up to 24 weeks. The difference between SHR and WKY may depend on the more severe cerebral blood flow depletion during carotid ligation in the former. The chronic state of SHR after the transient ischemia may be a useful pathophysiological model for human cerebral infarctions with hypertension.

Original languageEnglish
Pages (from-to)60-68
Number of pages9
JournalBrain Research
Volume712
Issue number1
DOIs
Publication statusPublished - Mar 11 1996

Keywords

  • Acetylcholine
  • Acetylcholine esterase
  • Choline acetyltransferase
  • Muscarinic M1-receptor
  • Spontaneously hypertensive rat
  • Transient ischemia

ASJC Scopus subject areas

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

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