Abstract |
To investigate the mechanisms underlying the neuroprotective effect of L-serine, permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery while monitoring cerebral blood flow (CBF). Rats were divided into control and L-serine-treated groups after middle cerebral artery occlusion. The neurological deficit score and brain infarct volume were assessed. Nissl staining was used to quantify the cortical injury. L-serine and D- serine levels in the ischemic cortex were analyzed with high performance liquid chromatography. We found that L-serine treatment: 1) reduced the neurological deficit score, infarct volume and cortical neuron loss in a dose-dependent manner; 2) improved CBF in the cortex, and this effect was inhibited in the presence of apamin plus charybdotoxin while the alleviation of both neurological deficit score and infarct volume was blocked; and 3) increased the amount of L-serine and D- serine in the cortex, and inhibition of the conversion of L-serine into D- serine by aminooxyacetic acid did not affect the reduction of neurological deficit score and infarct volume by L-serine. In conclusion, improvement in regional CBF by L-serine may contribute to its neuroprotective effect on the ischemic brain, potentially through vasodilation which is mediated by the small- and intermediate-conductance Ca(2+)-activated K(+) channels on the cerebral blood vessel endothelium.
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Authors | Tao-Jie Ren, Ren Qiang, Zheng-Lin Jiang, Guo-Hua Wang, Li Sun, Rui Jiang, Guang-Wei Zhao, Le-Yang Han |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 6
Pg. e67044
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23825613
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Neuroprotective Agents
- Potassium Channels, Calcium-Activated
- Charybdotoxin
- Apamin
- Serine
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Topics |
- Animals
- Apamin
(pharmacology)
- Cerebrovascular Circulation
(drug effects)
- Charybdotoxin
(pharmacology)
- Dose-Response Relationship, Drug
- Drug Interactions
- Endothelium, Vascular
(drug effects)
- Infarction, Middle Cerebral Artery
(metabolism, physiopathology)
- Male
- Neuroprotective Agents
(pharmacology)
- Potassium Channels, Calcium-Activated
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Serine
(antagonists & inhibitors, pharmacology)
- Time Factors
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