Long-term potentiation saturation in chronic cerebral hypoperfusion

Chronic reductions in cerebral blood flow (CBF) of between 25 and 50%, in the absence of cerebral infarction, lead to impairments in hippocampal in vitro long-term potentiation (LTP). This study set out to explore some of the properties of this impairment of LTP. LTP is an electrophysiological property known to occur in the hippocampus, a region known to be exquisitely sensitive to hypoxic or ischemic insults. Thus, assessing LTP is a novel way of assessing the effects of subtle ischemic insults. Five male Sprague-Dawley rats had arteriovenous fistulae created surgically in the neck to induce a state of chronic cerebral hypoperfusion (CCH) with the features described above. Five rats were used as age-matched controls. Twenty-six weeks after fistula formation, the animals were prepared for in vitro hippocampal recording in a submerged tissue bath. Extracellular field potentials were recorded at the Schaffer collateral-CA1 region, with a stimulus intensity that achieved a population spike amplitude of 1 mV. After tetanic stimulation, the frequency and magnitude of LTP was compared between control and fistula animals. All animals in both these groups demonstrated LTP in contradistinction to our previous work where LTP was impaired in fistula animals when a higher intensity of stimulation was used. This indicates that the structures that are associated with the initiation and maintenance of LTP (most probably the ischemia-sensitive CA1 pyramidal cells) are saturated as the stimulus intensity is increased. Thus, at this lower intensity of stimulation LTP is preserved in the fistula animals, but found to be impaired as the stimulus intensity is increased. Consequently, this study provides further information on this newly identified subtype of chronic cerebral ischemia which, in time, after further studies in humans, may help to redefine therapeutic indicators for the management of cerebral arteriovenous malformation and severe cerebrovascular disease.