ALTERATION OF PROTEIN-KINASE-C ACTIVITY AFTER TRANSIENT FOCAL CEREBRAL-ISCHEMIA IN MICE USING IN-VITRO [H-3] PHORBOL-12,13-DIBUTYRATE BINDING AUTORADIOGRAPHY

Changes in the regional distribution of protein kinase C (PKC) after t ransient focal cerebral ischemia in SV-129 mice were assessed by quant itative autoradiography using [H-3]phorbol-12,13-dibutyrate ([H-3]PDBu ) binding. [H-3]PDBu binding did not change up to 10 min after reperfu sion of 3 h ischemia, but at 1 h after reperfusion markedly decreased to 40-50% of control (pre-ischemia) in the ipsilateral striatum and th e middle cerebral artery (MCA) region of cortex in SV-129 mice. The bi nding decreased to 20% of control at 3-7 days after reperfusion, but d id not change in the ipsilateral anterior cerebral artery (ACA) territ ory or the contralateral brain. In the ipsilateral substantia nigra, w hich lies outside the ischemic zone, [H-3]PDBu binding was not signifi cantly changed compared to the control values (pre-ischemia) at early phase (up to 3 h after reperfusion), but marked reduction of the bindi ng was observed 1 day after reperfusion. After 3 h ischemia followed b y 3 h reperfusion, the morphological damage and the decrease in [H-3]P DBu binding in the ipsilateral striatum and the MCA region of cortex w as smaller in mice lacking the expression of neuronal nitric oxide syn thase (type I NOS) gene mutant mice compared to wild-type (SV-129 and C57black/6) mice. Our data suggest that postischemic alterations of PK C binding activity were observed in the ischemic and non-ischemic lesi ons in the mouse brain. (C) 1997 Elsevier Science B.V.