Neuroprotective effect of L-serine on rats with permanent middle cerebral artery occlusion

AIM: To investigate the neuroprotective effect, therapeutic dosage and time window of L-serine against permanent cerebral injury in rats. METHODS: Permanent middle cerebral artery occlusion (pMCAO) was induced in the rats to determine the efficacy of L-serine (ip) by neurological evaluation, TTC staining and Nissl staining.L-serine was used at different doses (56 mg/kg, 168 mg/kg and 504 mg/kg) and for different time periods (1 h, 3 h, 6 h, 12 h and 24 h after pMCAO). Aminooxyacetic acid (AOAA), an inhibitor of serine racemase, was used to alter the efficacy of L-serine. Laser Doppler perfusion monitor was used to observe the regional cerebral blood flow (rCBF) in the ischemic cerebral cortex under the condition with or without L-serine treatment. RESULTS: Treatment with L-serine at doses of 168 mg/kg and 504 mg/kg at time point of 3 h after pMCAO greatly decreased the neurological deficit score and infarct volume,and attenuated the loss of hippocampal CA1 neuronal cells. In the observation of therapeutic time window, L-serine displayed a significant neuroprotective effect if used within 6 h after pMCAO, but did not exert any notable effect if used over 12 h after pMCAO. AOAA hardly changed the effect of L-serine. L-serine treatment notably raised rCBF in the area of ischemic cerebral cortex when it was injected 30 min after pMCAO. However, strychnine, an antagonist of strychnine-sensitive glycine receptor, did not alter this effect of L-serine. CONCLUSION: L-serine has neuroprotective effect on permanent ischemic brain injury in rats if administered early and sufficiently by augmentation of rCBF in the ischemic cerebral cortex.