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Nitric Oxide Production and Long-term Potentiation in the Rat Hippocampus Following Transient Cerebral Ischemia

Conference paper

Summary

The cerebral dysfunction such as deterioration of memory remains serious complications of ischemic reperfusion injury. Long-term potentiation (LTP) has been widely studied as a form of synaptic plasticity that represents a cellular mechanism of learning and memory. Numerous processes and molecules are reported to be involved in LTP mechanisms, and some elements including neurotrophic and transcription factors are likely to be common with those involved in neural death after cerebral ischemia. Nitric oxide (NO) is a molecule which has crucial roles in neuronal injury. In our study, we focused on LTP formation as a functional response to cerebral ischemia and elucidated the implication of NO production in LTP formation in the rat hippocampus following transient cerebral ischemia. NO production was evaluated by oxidative NO metabolite levels determined using in vivo brain microdialysis. Transient cerebral ischemia produced a marked inhibition of LTP in both Schaffer-CAl synapses and perforant path-dentategyrus synapses. The increase in hippocampal NO production was observed to precede LTP inhibition. Direct or indirect inhibition of an inducible NO synthase (iNOS) rescued ischemia-induced LTP inhibition. Centrally administered bacterial endotoxin, lipopolysaccharide, which is known to induce iNOS expression, could mimic the time-course changes in hippocampal NO production observed after ischemic insult. These findings suggest that iNOS-derived NO is partly responsible for the ischemia-induced impairment of LTP in the rat hippocampus.

Key Words

Cerebral ischemia Long-term potentiation Nitric oxide Hippocampus 

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Copyright information

© Springer Japan 1999

Authors and Affiliations

  1. 1.Department of PharmacologyHokkaido University Graduate School of MedicineSapporoJapan
  2. 2.Department of AnesthesiologyHokkaido University School of MedicineSapporoJapan

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