Expression of zinc finger immediate early genes in rat brain after permanent middle cerebral artery occlusion

Jari Honkaniemi, Bradley A. States, Philip R. Weinstein, Jose Espinoza, Frank R Sharp

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


The prolonged expression of the leucine zipper fos/jun immediate early genes (IEG) has been correlated with neuronal death after cerebral ischemia. In this study, the expression of six zinc finger lEG was examined using in situ hybridization in adult rats after middle cerebral artery occlusion (MCAO) with the suture model, NGFI-A, NGFI-B, NGFI-C, egr-2, egr-3, and Nurrl mRNA were all induced throughout the ipsilateral cortex at 1 hour to 12 hours after MCAO. The cortical induction for most of the genes was greatest in the anterior cingulate and the anterior cerebral artery (ACA) and middle cerebral artery (MCA) transition zone. All of the zinc finger lEG were induced at 1 hour in all regions of hippocampus. NGFI-A and NGFI-B were induced in ipsilateral thalamus. Within areas of infarction, the basal IEG mRNA expression, and expression of the housekeeping gene cyclophilin A mRNA, decreased below control levels by 12 hours after the ischemia. Immediate early gene expression outside areas of infarction returned to control levels in most brain regions by 24 hours except for egr-3, which continued to be induced in the MCA/ACA transition zone for 24 hours, and NGFI-A, which continued to be expressed in specific regions of the thalamus for 72 hours. The induction of these IEG in the cortex is likely caused by ischemia- induced cortical spreading depression, with the hippocampal and thalamic IEG induction being caused by activation of efferent conical pathways to these regions. The prominent induction of NGFI-B, NGFI-C, egr-2, and egr-3 in the anterior cingulate cortex, the ACA/MCA transition zone, and medial striatum could reflect the ischemic regions around MCA infarcts. The prolonged NGFI-A expression observed in thalamus in this study, and in CA 1 of hippocampus after global ischemia in the gerbil in a previous study, suggests that the prolonged NGFI-A expression could be the result of or the cause of the delayed cell death. Prolonged NGFI- A expression, like c-fos and c-jun, seems to provide a marker for slowly dying neurons.

Original languageEnglish (US)
Pages (from-to)636-646
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number6
StatePublished - Jun 1997
Externally publishedYes


  • Apoptosis
  • Glutamate
  • Hippocampus
  • In situ hybridization
  • Neuronal death
  • Rat

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism


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