The role of nitric oxide in the development of cortical spreading depression-induced tolerance to transient focal cerebral ischemia in rats

Takashi Horiguchi, James A. Snipes, Bela Kis, Katsuyoshi Shimizu, David W. Busija

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Cortical spreading depression (CSD) has been documented to confer ischemic tolerance on brain. Although nitric oxide (NO) is a crucial mediator in preconditioning under certain circumstances, the role of NO in CSD-induced neuroprotection is unclear. We examined the effect of L-NAME, an inhibitor of NO synthase, on CSD-induced tolerance against transient focal cerebral ischemia. A solution of 0.5 M KCl was applied for 2 h on the right hemisphere to induce CSD. Animals received either vehicle or L-NAME (4 mg/kg, iv) 30 min before CSD. Temporary occlusion (120 min) of the right middle cerebral artery was induced 4 days after preconditioning and the infarct volume was measured. Additionally, ERK 1/2 activation and cyclooxygenase-2 (COX-2) expression in the cerebral cortex were examined by Western blotting analysis immediately after cessation of CSD, or at 1, 2, 4, 8, and 24 h after CSD. CSD reduced infarct volume from 275 ± 15 mm3 (mean ± SEM) in the non-CSD group to 155 ± 14 mm3 in the CSD group (P < 0.05). L-NAME abolished this protection (281 ± 14 mm3; P < 0.05 vs. CSD group). Elevated ERK activation and COX-2 expression were observed immediately after or 8 h after preconditioning, respectively. Those responses are significantly augmented by L-NAME (3-fold for ERK and 4-fold for COX-2). These results suggest a crucial role of NO in the establishment of preconditioning with CSD.

Original languageEnglish
Pages (from-to)84-89
Number of pages6
JournalBrain Research
Volume1039
Issue number1-2
DOIs
Publication statusPublished - 2005 Mar 28
Externally publishedYes

Keywords

  • Brain ischemia
  • Cerebral blood flow
  • Cerebral circulation
  • Cerebral ischemia, transient
  • Cyclooxygenase
  • Ischemic preconditioning

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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