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 NG-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 neutoprotective 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 < 0.05) 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 or MK-801.
Margaill
I
I
Laboratoire de Pharmacologie, Université René Descartes, Paris, France.
Allix
M
M
Boulu
R G
RG
Plotkine
M
M
D000818:Animals; D001784:Blood Gas Analysis; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester