Chronic cerebral hypoperfusion and impaired neuronal function in rats

Lali H S Sekhon, Michael K. Morgan*, Ian Spence, Neville C. Weber

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

Background and Purpose: Studies in acute cerebral ischemia have shown that reductions in cerebral blood flow of up to 50% do not lead to infarction or alterations in neuronal electric activity. Little is known about the effects of chronic reductions in cerebral blood flow. The purpose of this study was to evaluate neuronal electrophysiological function in brain that had been subjected to a chronic reduction of cerebral blood flow of less than 50%. Based on existing knowledge of thresholds of cerebral ischemia, neuronal electrophysiological function should be unaffected by hypoperfusion of this magnitude. Methods An arteriovenous fistula model in the rat was used to induce chronic cerebral hypoperfusion with reductions of cerebral blood flow of 25% to 50% as measured previously by 14C-labeled autoradiography. Using in vitro electrophysiological brain slice techniques, long-term potentiation in hippocampal CA1 neurons was examined extracellularly after 6 months of chronic noninfarctional cerebral hypoperfusion. Brains were also examined histologically at this time for evidence of cerebral infarction. Results There was no evidence of cerebral infarction. Longterm potentiation was produced in 9 of 12 control animals and only 2 of 8 hypoperfused animals. This difference was significant (P<.05) and demonstrated that long-term potentiation was impaired in animals with chronic hypoperfusion. Conclusions Noninfarctional reductions in cerebral blood flow of up to 50% do impair neuronal function in chronic cerebral ischemia, a result quite distinct from that seen in acute ischemia. The threshold for neuronal dysfunction in chronic cerebral hypoperfusion is lower than that found in acute cerebral ischemia, suggesting that duration as well as severity of ischemic insult determines cellular viability. Chronic hypoperfusion may lead to a noninfarctional state with impaired neuronal function, a category of chronic cerebral ischemia not previously identified.

Original languageEnglish
Pages (from-to)1022-1027
Number of pages6
JournalStroke
Volume25
Issue number5
Publication statusPublished - 1994
Externally publishedYes

Keywords

  • Arteriovenous fistula
  • Cerebral ischemia
  • Hippocampus
  • Rats

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