Neuroprotective effect of L-serine against temporary cerebral ischemia in rats.
To investigate the neuroprotective effect of L-serine and its underlying mechanisms, focal cerebral ischemia was induced in rats by occlusion of middle cerebral artery (MCAO) with a suture, and reperfusion was given by filament withdrawal 2 hr later. Meanwhile, rat hippocampal neurons were primarily cultured, and incubated in serum-free medium in an incubator containing 1% O(2) for hypoxic exposure of 5 hr, or incubated in serum-free medium containing 1 mM glutamate for glutamate exposure of 2 hr. Brain tissue injury and cell damage were then measured. L-serine dose-dependently decreased the neurology deficit score and infarct volume, elevated the cell viability and inhibited the leakage of lactate dehydrogenase. These effects were blocked by strychnine in both MCAO rats and cultured hippocampal neurons. Furthermore, L-serine (168 mg.kg(-1)) reduced the brain water content, permeability of blood-brain barrier, neuronal loss and the expression of activated caspase-3 in the cortex. In addition, L-serine effectively protected the brain from damage when it was administered within 6 hr after the end of MCAO. It is suggested that L-serine could exert a neuroprotective effect on the ischemic-reperfused brain and on the hypoxia- or glutamate-exposed hippocampal neurons, which may be mediated by activating glycine receptors.
Wang
Guo-Hua
GH
Department of Neuropharmacology, Institute of Nautical Medicine, Nantong University, Nantong, China.
Jiang
Zheng-Lin
ZL
Chen
Zhao-Qin
ZQ
Li
Xia
X
Peng
Liang-Liang
LL
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D018684:Glycine Agents / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000008:administration & dosage / Q000494:pharmacology*; D013331:Strychnine / Q000494:pharmacology; D013997:Time Factors
D018684:Glycine Agents; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D012694:Serine; D013331:Strychnine