DOSE-DEPENDENCE AND TIME-DEPENDENCE OF L-NAME NEUROPROTECTION IN TRANSIENT FOCAL CEREBRAL-ISCHEMIA IN RATS

1 In this study the effect of the dose and administration time of N-G- nitro-L-arginine methyl ester (L-NAME), an NO-synthase inhibitor, in a model of transient focal cerebral ischaemia in rats was investigated. 2 Two injections of L-NAME were given, of 1, 3 and 10 mg kg(-1), 5 mi n and 3 h after the onset of ischaemia. None of the doses gave any str iatal neuroprotection, but 1 and 3 mg kg(-1) L-NAME reduced the infarc ted volume in the cortex (by 26%, P<0.01 for 1 mg kg(-1) and 21%, P<0. 05 for 3 mg kg(-1)), whereas 10 mg kg(-1) had no neuroprotective effec t. 3 Single injections of L-NAME 1 mg kg(-1), given 5 min or 3 h after ischaemia onset, had similar neuroprotective effects on the cortical infarction as did the repeated injections. 4 L-NAME 1 mg kg(-1) given 3, 6 or 9 h after ischaemia induction reduced the cortical infarct vol ume by 19% (P<0.01) when given 3 h after ischaemia, by 21% (P<0.01) wh en given at 6 h, and by 16% (P<0.5) when given at 9 h, but had no neur oprotective activity when given 12 h after ischaemia. 5 Thus a low dos e of L-NAME is neuroprotective in a model of transient focal ischaemia , with a wide therapeutic window, much larger than that found for MK-8 01.