[Experimental study of therapeutic time window of L-serine against focal cerebral ischemia/reperfusion injury in rats].
OBJECTIVE
To observe the therapeutic time window of L-serine against focal cerebral ischemia/reperfusion injury in rats, and related mechanisms.


METHODS
Sprague-Dawley rats were randomly divided into six groups (n=6), sham-operation group, vehicle group, 3, 6, 12 and 24 h treatment group of L-serine. Focal cerebral ischemia was induced with the method of middle cerebral artery occlusion (MCAO) in rats, and reperfusion was emerged by removing the thread 2 h later. The treatment of L-serine (200 mg/kg ip) was begun at 3, 6, 12 and 24 h after MCAO respectively, and subsequently repeated once 12 h. The vehicle group was intraperitoneally injected with isodose normal saline. The neurological behavior score and cerebral infarction volume was measured 48 h after reperfusion. In addition, the contents of malondialdehyde (MDA), activity of superoxide dismetase (SOD), the levels of inflammatory cytokines (TNF-alpha, IL-6) and ultrastructure of neuron in brain tissue were investigated.


RESULTS
Compared with the vehicle group, treatments with L-serine both 3 and 6 h after MCAO decreased the neurology deficit score and infarct volume. Only neurology deficit score had been reduced 12 h after MCAO, while no neuropmrotective effects had been observed during 24 h. Furthermore, L-serine elevated the content of SOD, decreased the level of MDA, TNF-alpha and IL-6 in ischemic brain tissue, and alleviated the injury of the neuronal ultrastructure.


CONCLUSIONS
L-serine exerted a time-dependent neuroprotective effect on the brain after MCAO in rat. This effect might be possibly mediated through following mechanisms: lessening oxidative stress and reducing the release of inflammatory cytokines.
Wang
Guo-hua
GH
Institute of Nautical Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China.
Jiang
Zheng-lin
ZL
Zhang
Xiang-gen
XG
Shen
Li-hua
LH
Fan
Xing-juan
XJ
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D012694:Serine / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D012694:Serine; D013482:Superoxide Dismutase