Dose- and time-dependence of L-NAME neuroprotection in transient focal cerebral ischaemia 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 min and 3 h after the onset of ischaemia. None of the doses gave any striatal neuroprotection, but 1 and 3 mg kg(-1) L-NAME reduced the infarcted 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 effect. 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 volume by 19% (P<0.01) when given 3 h after ischaemia, by 21% (P<0.01) when given at 6 h, and by 16% (P<0.5) when given at 9 h, but had no neuroprotective activity when given 12 h after ischaemia. 5 Thus a low dose of L-NAME is neuroprotective in a model of transient focal ischaemia, with a wide therapeutic window, much larger than that found for MK-801.