ROLE OF INHIBITION IN CHRONIC CEREBRAL HYPOPERFUSION

Chronic reductions in cerebral blood flow (CBF) of between 25 and 50% maintained for 26 weeks impair neuronal function, through a mechanism which is not known, but which is now explored. Increased GABAergic syn aptic inhibition may play a role, as inhibitory interneurons are known to be relatively resistant to acute ischaemic insults. The phenomenon of tetanus-induced longterm potentiation (LTP) was previously found t o be impaired in this setting, and was thus examined in the in vitro r at hippocampus in the presence of bicuculline, a specific GABA(A) anta gonist, to evaluate the role of inhibition in the impairment of LTP in chronic cerebral hypoperfusion (CCH). Nine Sprague-Dawley rats aged 8 -10 weeks had arteriovenous fistulae (AVF) surgically constructed to r educe CBF to between 25 and 50%. Ten animals were used as age-matched controls. After a further 26 weeks, 400 mu m hippocampal slices were p repared. Tetanic stimulation was used in order to attempt to induce LT P. In vitro extracellular field potentials from control and AVF slices with 5 x 10(-6) M bicuculline exposure and subsequent tetanic stimula tion were compared. There was no statistical difference between the re sponses of the two groups in either scenario (P > 0.05), although LTP was in general more difficult to induce (only occurring in 60% of cont rol animals). Possible causes of this are discussed. It is concluded t hat increased GABAergic synaptic inhibition does not play a role in im pairment of neuronal function seen after 26 weeks of non-infarctional CCH. Journal of Clinical Neuroscience (1998) 5(4), 423-428 (C) Harcour t Brace & Co. Ltd 1998