Dose‐ and time‐dependence of l ‐NAME neuroprotection in transient focal cerebral ischaemia in rats

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. 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. 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.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. 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.British Journal of Pharmacology (1997) 120 , 160–163; doi: 10.1038/sj.bjp.0700889