IN-VIVO BINDING OF [H-3] NIMODIPINE IN RAT-BRAIN AFTER TRANSIENT FOREBRAIN ISCHEMIA

We report the regional variation in relative in vivo binding of the L- type voltage sensitive calcium channel (VSCC) antagonist H-3nimodipi ne to brain following transient forebrain ischemia in the rat. At 30-m in of reperfusion after 20 min of forebrain ischemia, H-3nimodipine binding was significantly increased in striatum, CA3 and CA4, and dent ate relative to binding in sham-operated rats, suggesting that VSCCs w ere responding to ischemic depolarization. Two h following ischemia, b inding in all brain structures returned to normal levels indicating re polarization of cell membranes. At 24 h of recirculation, increased H -3nimodipine binding was again observed in striatum and dentate. Bind ing remained elevated in the striatum and dentate, and increased bindi ng became evident in the CA1 region of the hippocampus after 48 h of r eperfusion. With the exception of the dentate gyrus, the second rise i n H-3nimodipine binding anticipated or coincided with the observed r egional ischemic cell changes. These observations in global cerebral i schemia support previous work indicating that in vivo binding of H-3 nimodipine to the L-type VSCC may be an early and sensitive indicator of impending ischemic injury. Such measurements may be of use in ident ifying vulnerable brain regions and defining a therapeutic window of o pportunity in models of cerebral ischemia.