CHRONIC CEREBRAL HYPOPERFUSION INHIBITS CALCIUM-INDUCED LONG-TERM POTENTIATION IN RATS

Background and Purpose Long-term potentiation (LTP) in the rat hippoca mpus induced by tetanic stimulation is impaired by chronic cerebral hy poperfusion. The effects of chronic cerebral hypoperfusion on other fo rms of LTP are unknown. Such data could help delineate the pathways of cellular alteration caused by chronic cerebral hypoperfusion. The in vitro phenomenon of calcium-induced LTP was thus examined in rat hippo campal CA1 cells that had undergone chronic hypoperfusion with a reduc tion in cerebral blood flow of between 25% and 50% maintained for 26 w eeks. Methods Ten Sprague-Dawley rats had a cervical arteriovenous fis tula surgically constructed, and an additional 10 animals were used as age-matched controls. Hippocampal slices were prepared after 26 weeks of hypoperfusion, and in vitro extracellular field potential recordin gs were taken from the Schaffer collateral CA1 region. Properties of L TP induced through transient exposure to a hypercalcemic solution were analyzed. Results LTP was impaired in animals with an arteriovenous f istula (P<.05). Control animals demonstrated potentiation lasting for the entire 2 hours of recording, whereas fistula animals showed only t ransient potentiation (<60 minutes) before returning to baseline value s. Conclusions Calcium-induced LTP is impaired by chronic cerebral hyp operfusion. This form of LTP is different from that induced by tetanic stimulation. It is the most sensitive test available for in vitro det ection of the changes induced in neuronal function by chronic noninfar ctional reductions in cerebral blood flow of 25% to 50% and may indica te that the most basic cellular parameters involving calcium homeostas is and metabolism are being altered. The precise mechanisms remain to be elucidated, and several postulates are discussed.