Involvement of interleukin-1 beta/nitric oxide pathway in the postischemicimpairment of long-term potentiation of the rat hippocampus

To investigate whether postischemic cerebral dysfunction occurs via the int erleukin-1 beta/nitric oxide (IL-1 beta /NO) pathway, we examined the effec ts of an IL-1 beta antagonist on long-term potentiation (LTP) impairment an d excessive NO production in the rat hippocampus after 10-min global ischem ia. Intracerebroventricilar administration of the IL-1 beta antagonist atte nuated NO production and rescued LTP impairment in the perforant path-denta te gyrus synapses, observed 1 day and 4 days after ischemic insult, respect ively. There was an inverse relationship between LTP in the dentate gyrus s ynapses and hippocampal NO production. Centrally applied IL-1 beta mimicked the consequences of transient ischemia in LTP formation and hippocampal NO production in non-ischemic rats. These findings indicate that the IL-1 bet a /NO pathway is involved in the hippocampal LTP impairment observed in the postischemic brain. (C) 2001 Elsevier Science Ireland Ltd. All rights rese rved.