FK506 abrogates delayed neuronal death via suppression of nitric oxide production in rats

Takahiro Sasaki, Junichi Hamada, Mamoru Shibata, Jun Gotoh, Nobuo Araki, Yasuo Fukuuchi

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Background and purpose: The mechanism of the neuroprotective effect of FK506 in relation to nitric oxide (NO) production has not been clarified in vivo. We have investigated the effect of FK506 on ischemia-induced NO production in association with the pathogenesis of delayed neuronal death (DND) in rats. Methods: In vivo microdialysis was performed in the hippocampus of male Sprague-Dawley rats (250-350 g). Dialysate samples were collected every 3 min. In the ischemia group (n=16), global ischemia was induced for 21 min and reperfusion was achieved. In the FK506 treatment group (n=25), FK506 (1 mg/kg, i.v.) was administered 21 min prior to the onset of global ischemia. Sham operations were done (n=15). The levels of NO2- in the dialysate samples were determined by the Griess reaction. The animals were decapitated 7 days after ischemia. Coronal brain sections were stained with hematoxylin and eosin. Results: In the ischemia group, the NO2 - level significantly increased during ischemia. In the FK506 treatment group, there was no significant change in the NO2 - level during ischemia. In histological examinations, FK506 treatment showed a neuroprotective effect against DND. Conclusions: The effect of FK506 inhibiting NO production contributes to the neuro-protective effect of FK506 on DND in the hippocampus.

Original languageEnglish
Pages (from-to)34-39
Number of pages6
JournalBrain Research
Issue number1-2
Publication statusPublished - 2004 May 29
Externally publishedYes


  • Cerebral ischemia
  • Disorders of the nervous system
  • Global
  • Hippocampus
  • Ischemia
  • Microdialysis
  • Nitric oxide
  • Rat

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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