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 language | English |
|---|---|
| Pages (from-to) | 84-89 |
| Number of pages | 6 |
| Journal | Brain Research |
| Volume | 1039 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - 2005 Mar 28 |
| Externally published | Yes |
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Keywords
- Brain ischemia
- Cerebral blood flow
- Cerebral circulation
- Cerebral ischemia, transient
- Cyclooxygenase
- Ischemic preconditioning
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
The role of nitric oxide in the development of cortical spreading depression-induced tolerance to transient focal cerebral ischemia in rats. / Horiguchi, Takashi; Snipes, James A.; Kis, Bela; Shimizu, Katsuyoshi; Busija, David W.
In: Brain Research, Vol. 1039, No. 1-2, 28.03.2005, p. 84-89.Research output: Contribution to journal › Article
}
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.
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
UR - http://www.scopus.com/inward/record.url?scp=15244362218&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=15244362218&partnerID=8YFLogxK
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 - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -