Post-ischemic administeration but not pre-ischemic 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, F. Pu, T. Kaneko, N. Egashira, K. Iwasaki, M. Fujiwara

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In the present study, we investigated the effects of NG-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 NOx- 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 NOx- 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 NOx- may cause spatial memory impairment and induction of apoptosis in the hippocampus in rats subjected to repeated ischemia.

Original languageEnglish
Pages (from-to)533-540
Number of pages8
JournalNeuropharmacology
Volume44
Issue number4
DOIs
Publication statusPublished - Mar 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Post-ischemic administeration but not pre-ischemic administeration of N<sup>G</sup>-nitro-L-arginine prevents spatial memory impairments and apoptosis by an inhibition of a delayed increase in NO<sub>x</sub><sup>-</sup> in the hippocampus following repeated cerebral ischemia'. Together they form a unique fingerprint.

  • Cite this