title: 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.
authors.affiliation: Department of Neuropharmacology, Institute of Nautical Medicine, Nantong University, Nantong, Jiangsu Province, China.
authors.forename: Tao-Jie
authors.initials: TJ
authors.lastname: Ren
authors.forename: Ren
authors.initials: R
authors.lastname: Qiang
authors.forename: Zheng-Lin
authors.initials: ZL
authors.lastname: Jiang
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Jiang
authors.forename: Guang-Wei
authors.initials: GW
authors.lastname: Zhao
authors.forename: Le-Yang
authors.initials: LY
authors.lastname: Han
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D018999:Charybdotoxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin; D001030:Apamin; D012694:Serine