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. 2003 Mar;44(4):533-40.
doi: 10.1016/s0028-3908(02)00404-5.

Post-ischemic administration [correction of administeration] but not pre-ischemic administration [correction of administeration] of NG-nitro-L-arginine prevents spatial memory impairments and apoptosis by an inhibition of a delayed increase in NOx- in the hippocampus following repeated cerebral ischemia

K Mishima  1 , F Pu, T Kaneko, N Egashira, K Iwasaki, M Fujiwara
Affiliations

Post-ischemic administration [correction of administeration] but not pre-ischemic administration [correction of administeration] of NG-nitro-L-arginine prevents spatial memory impairments and apoptosis by an inhibition of a delayed increase in NOx- in the hippocampus following repeated cerebral ischemia

K Mishima et al. Neuropharmacology. 2003 Mar.

Abstract

In the present study, we investigated the effects of N(G)-nitro-L-arginine (L-NAME), an inhibitor of nitric oxide synthase, on repeated cerebral ischemia-induced impairment of spatial memory of the 8-arm radial maze in rats. Repeated ischemia (10 min ischemia x 2 times with 1 h interval) impaired the spatial memory in the 8-arm radial maze test and produced apoptosis in the hippocampus 7 days after final occlusion, and gradually increased the NO(x)(-) levels approximately 30-180 min after the second reperfusion. Post-ischemic administration of L-NAME at a dose of 50 mg/kg, i.p. 30 min following the second occlusion, significantly attenuated the repeated ischemia-induced impairment of spatial memory in the 8-arm radial maze test and suppressed apoptosis in the hippocampus, and also significantly suppressed a delayed increase in the NO(x)(-) levels induced by repeated ischemia. However, pre-ischemic administration of L-NAME at a dose of 50 mg/kg, i.p. 30 min before the first occlusion, caused about 90% mortality (the mortality rate of vehicle-treated group was 10%). These results suggest that the delayed generation of NO(x)(-) may cause spatial memory impairment and induction of apoptosis in the hippocampus in rats subjected to repeated ischemia.

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