TY - JOUR
T1 - The role of nitric oxide in the development of cortical spreading depression-induced tolerance to transient focal cerebral ischemia in rats
AU - Horiguchi, Takashi
AU - Snipes, James A.
AU - Kis, Bela
AU - Shimizu, Katsuyoshi
AU - Busija, David W.
N1 - Funding Information:
The authors acknowledge the helpful advice of Dr. Ryoichi Saito, National Tokyo Medical Center, concerning the experimental design and Nancy Busija, M.A., for aid in editing the manuscript. This work was supported by Grants HL30260, HL65380, HL66074, HL77731, and DK62372 from the National Institutes of Health and AHA Bugher Foundation Award 0270114N.
PY - 2005/3/28
Y1 - 2005/3/28
N2 - 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.
AB - 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.
KW - Brain ischemia
KW - Cerebral blood flow
KW - Cerebral circulation
KW - Cerebral ischemia, transient
KW - Cyclooxygenase
KW - Ischemic preconditioning
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U2 - 10.1016/j.brainres.2005.01.047
DO - 10.1016/j.brainres.2005.01.047
M3 - Article
C2 - 15781049
AN - SCOPUS:15244362218
VL - 1039
SP - 84
EP - 89
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1-2
ER -