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

Abstract

1 In this study the e ect 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 71 , 5 min and 3 h after the onset of ischaemia. None of the doses gave any striatal neuroprotection, but 1 and 3 mg kg 71 L-NAME reduced the infarcted volume in the cortex (by 26%, P50.01 for 1 mg kg 71 and 21%, P50.05 for 3 mg kg 71 ), whereas 10 mg kg 71 had no neuroprotective e ect. 3 Single injections of L-NAME 1 mg kg 71 , given 5 min or 3 h after ischaemia onset, had similar neuroprotective e ects on the cortical infarction as did the repeated injections. 4 L-NAME 1 mg kg 71 given 3, 6 or 9 h after ischaemia induction reduced the cortical infarct volume by 19% (P50.01) when given 3 h after ischaemia, by 21% (P50.01) when given at 6 h, and by 16% (P50.5) 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.

Methylene blue added to a hypertonic–hyperoncotic solution increases short-term survival in experimental cardiac arrest*

“…A possible mechanism by which neurotoxicity is induced is the formation of peroxynitrite anion (40,41). Thus, NOS inhibitors are considered to favor neuroprotection by inhibiting NO production, preventing neurotoxicity due to excess NO by scavenging oxygen-derived free radicals (41,42), which together may otherwise form peroxynitrite.…”

Reperfusion-Induced Oxidative/Nitrative Injury to Neurovascular Unit After Focal Cerebral Ischemia

“…15 Possibly because of this dual action of NO, high doses of NOS inhibitors increase infarct size, whereas low doses are protective. 33 Inhibition of peroxynitrite formation is also feasible by suppressing superoxide levels. In parallel to our results, Asahi et al found a decrease in reperfusion-induced vascular injury and reduction in hemorrhagic complications when a free radical scavenger was administered at reperfusion.…”

Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury

“…As stated above, a non-selective NOS inhibitor, L-NAME (Figure 1a), can reduce the infarction volume, prevent the BBB breakdown and improve the recovery of neurological functions in cerebral ischemic mouse models [118,119] . However, L-NAME also targets eNOS, which has protective effects during the ischemic process.…”