We used in-vivo and in-vitro autoradiography and 3H-nimodipine, a dihydropyridine calcium channel antagonist, to study rat brain at various intervals after focal cerebral ischemia. The severity of ischemia was graded by blood flow measurements performed at the same time in separate rats. We observed that in-vitro autoradiography was inadequate as a measns to study binding in focal cerebral ischemia, since the act of decapitation activated the cortical binding sites diffusely and the preceding focal ischemia became inapparent. Conversely, in-vivo a very dynamic picture of both regional and duration-dependent binding to nimodipine was evident. Comparison to CBF data indicated that the most ischemic regions show the earliest activation of nimodipine binding. As these regions lose their activation, more moderately ischemic regions exhibit activated binding. We therefore propose to test the hypothesis that loss of nimodipine binding in a previously acttivated region is associated with infarction, while slower but more persistent activation characterizes salvageable tissue. We then propose to compare control ischemia to the results obtained when calcium channel or NMDA receptor antagonists are administered after the onset of ischemia. Using positron-emitting 11C-nimodipine synthesized here, we propose to use PET to study the effect of varying ischemic severity on nimodipine binding in baboon brain and, with the same techniques, investigate the natural history of nimodipine binding in stroke patients.
