CHRONIC CEREBRAL HYPOPERFUSION AND IMPAIRED NEURONAL FUNCTION IN RATS

Background and Purpose Studies in acute cerebral ischemia have shown t hat reductions in cerebral blood flow of up to 50% do not lead to infa rction or alterations in neuronal electric activity. Little is known a bout the effects of chronic reductions in cerebral blood flow. The pur pose of this study was to evaluate neuronal electrophysiological funct ion in brain that had been subjected to a chronic reduction of cerebra l blood flow of less than 50%. Based on existing knowledge of threshol ds of cerebral ischemia, neuronal electrophysiological function should be unaffected by hypoperfusion of this magnitude. Methods An arteriov enous fistula model in the rat was used to induce chronic cerebral hyp operfusion with reductions of cerebral blood flow of 25% to 50% as mea sured previously by C-14-labeled autoradiography. Using in vitro elect rophysiological brain slice techniques, long-term potentiation in hipp ocampal CA1 neurons was examined extracellularly after 6 months of chr onic noninfarctional cerebral hypoperfusion. Brains were also examined histologically at this time for evidence of cerebral infarction. Resu lts There was no evidence of cerebral infarction. Longterm potentiatio n was produced in 9 of 12 control animals and only 2 of 8 hypoperfused animals. This difference was significant (P<.05) and demonstrated tha t long-term potentiation was impaired in animals with chronic hypoperf usion. Conclusions Noninfarctionai reductions in cerebral blood flow o f up to 50% do impair neuronal function in chronic cerebral ischemia, a result quite distinct from that seen in acute ischemia. The threshol d for neuronal dysfunction in chronic cerebral hypoperfusion is lower than that found in acute cerebral ischemia, suggesting that duration a s well as severity of ischemic insult determines cellular viability. C hronic hypoperfusion may lead to a noninfarctional state with impaired neuronal function, a category of chronic cerebral ischemia not previo usly identified.