OBJECTIVETo observe the therapeutic time window of L-serine against focal cerebral ischemia/reperfusion injury in rats, and related mechanisms.

METHODSSprague-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.

RESULTSCompared 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.

CONCLUSIONL-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.