Involvement of interleukin-1beta/nitric oxide pathway in the postischemic impairment of long-term potentiation of the rat hippocampus.
To investigate whether postischemic cerebral dysfunction occurs via the interleukin-1 beta/nitric oxide (IL-1beta/NO) pathway, we examined the effects of an IL-1beta antagonist on long-term potentiation (LTP) impairment and excessive NO production in the rat hippocampus after 10-min global ischemia. Intracerebroventricilar administration of the IL-1beta antagonist attenuated NO production and rescued LTP impairment in the perforant path-dentate gyrus synapses, observed 1 day and 4 days after ischemic insult, respectively. There was an inverse relationship between LTP in the dentate gyrus synapses and hippocampal NO production. Centrally applied IL-1beta mimicked the consequences of transient ischemia in LTP formation and hippocampal NO production in non-ischemic rats. These findings indicate that the IL-1beta/NO pathway is involved in the hippocampal LTP impairment observed in the postischemic brain.
Togashi
H
H
Department of Pharmacology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, 060-8638, Sapporo, Japan.thiro@med.hokudai.ac.jp
Mori
K
K
Itoh
Y
Y
Matsumoto
M
M
Ueno
K
K
Ohashi
S
S
Otani
H
H
Yoshioka
M
M
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D002339:Carotid Arteries / Q000502:physiology; D018891:Dentate Gyrus / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D053583:Interleukin-1beta; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009569:Nitric Oxide / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D019580:Perforant Pathway / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
D007375:Interleukin-1; D053583:Interleukin-1beta; D010446:Peptide Fragments; C056932:interleukin 1beta (193-195); D009569:Nitric Oxide