Altered Mitochondrial Respiration in Selectively Vulnerable Brain Subregions Following Transient Forebrain Ischemia in the Rat

Neil R. Sims, William A. Pulsinelli

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138 Citations (Scopus)

Abstract

Abstract: Mitochondrial respiratory function, assessed from the rate of oxygen uptake by homogenates of rat brain subregions, was examined after 30 min of forebrain ischemia and at recirculation periods of up to 48 h. Ischemia‐sensitive regions which develop extensive neuronal loss during the recirculation period (dorsal‐lateral striatum, CA1 hippocampus) were compared with ischemia‐resistant areas (paramedian neocortex, CA3 plus CA4 hippocampus). All areas showed reductions (to 53–69% of control) during ischemia for oxygen uptake rates determined in the presence of ADP or an uncoupling agent, which then recovered within 1 h of cerebral recirculation. In the ischemia‐resistant regions, oxygen uptake rates remained similar to control values for at least 48 h of recirculation. After 3 h of recirculation, a significant decrease in respiratory activity (measured in the presence of ADP or uncoupling agent) was observed in the dorsal‐lateral striatum which progressed to reductions of greater than 65% of the initial activity by 24 h. In the CA 1 hippocampus, oxygen uptake rates were unchanged for 24h, but were significantly reduced (by 30% in the presence of uncoupling agent) at 48 h. These alterations parallel the development of histological evidence of ischemic cell change determined previously and apparently precede the appearance of differential changes between sensitive and resistant regions in the content of high‐energy phosphate compounds. These results suggest that alterations of mitochondria activity are a relatively early change in the development of ischemic cell death and provide a sensitive biochemical marker for this process.

Original languageEnglish
Pages (from-to)1367-1374
Number of pages8
JournalJournal of Neurochemistry
Volume49
Issue number5
DOIs
Publication statusPublished - Nov 1987
Externally publishedYes

Keywords

  • Ischemia
  • Mitochondria
  • Oxygen uptake

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