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Improvement in regional CBF by L-serine contributes to its neuroprotective effect in rats after focal cerebral ischemia.

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.
AuthorsTao-Jie Ren, Ren Qiang, Zheng-Lin Jiang, Guo-Hua Wang, Li Sun, Rui Jiang, Guang-Wei Zhao, Le-Yang Han
JournalPloS one (PLoS One) Vol. 8 Issue 6 Pg. e67044 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID23825613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Neuroprotective Agents
  • Potassium Channels, Calcium-Activated
  • Charybdotoxin
  • Apamin
  • Serine
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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