The influence of delayed postischemic hyperthermia following transient focal ischemia: Alterations of gene expression

Young Kim, Jessie Truettner, Weizhao Zhao, Raul Busto, Myron D. Ginsberg

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

We have recently shown that moderate hyperthermia, even if delayed, markedly enlarges the volume of an acute ischemic infarct. In the current study, we used in situ hybridization autoradiography to assess the effects of delayed hyperthermia on the regional expression of messenger RNA (mRNA) for the immediate early genes c-fos and c-jun, the inducible heat-shock protein 70 (hsp 70) and glial fibrillary acid protein (GFAP) following 1 h of transient middle cerebral artery occlusion (MCAo) produced in rats by the insertion of an intraluminal suture. Sham-occluded rats were also studied. One day after MACo, rats were placed into a healing chamber, where cranial temperature was either maintained at 37-38°C (normothermic group) or was elevated to 40°C (hyperthermic group) for 3 h. At either 2 or 24 h thereafter, brains were studied by in situ hybridization. Low-level constitutive c-fos and c-jun expression in sham-occluded rats was unaffected by delayed temperature manipulation. Prior MCAo decreased c-fos and c-jun mRNA in the affected striatum and overlying cortex. In rats studied 2 h after delayed hyperthermia, however, c-fos mRNA was markedly increased in ipsilateral cingulate cortex. By contrast, the pattern of c-jun mRNA was similar in rats with prior MCAo irrespective of delayed normothermia or hyperthermia: increased expression involved ipsilateral cingulate and paramedian cortical areas. Bilateral increases in hsp70 expression were produced by hyperthermia alone, and hsp70 mRNA was densely increased throughout the ischemic cortex and striatum following MCAo, while delayed hyperthermia altered this pattern by extending the zone of increased hsp70 message to cingulate and paramedian cortical areas at 2 h. GFAP mRNA was decrease within the previously ischemic field but increased in surrounding regions. The induction of c-fos and hsp70 message in tissue regions abutting zones of enhanced injury in brains with delayed postischemic hyperthermia indicates that these zones have been additionally stressed: these gene responses may possibly contribute to the protection of these threatened regions.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalJournal of the Neurological Sciences
Volume159
Issue number1
DOIs
StatePublished - Jul 15 1998

Keywords

  • Autoradiography
  • Gene expression
  • Glial fibrillary acidic protein
  • Heat shock protein
  • Immediate early genes
  • In situ hybridization
  • Messenger RNA
  • Middle cerebral artery occlusion
  • Rat

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

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