Neuroprotective Effects Of Simvastatin Against Hypoxia-Ischemia Brain Damage In Neonatal Rats

Objective: To study on the mechanism of neuron death account for hypoxic-ischemic brain damage (HIBD) and neuroprotective effects of simvastatin in a neonatal cerebral cortex and hippocampus of HIBD.Methods: Postnatal 7-day-old SD rats were randomly divided into four groups: sham operation group(sham group), normal saline control group(HIBD group), citicoline control group(CDPC group) and simvastatin treated group. The expression of intercellular adhesion molecule-1(ICAM-1) mRNA and protein was detected by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry technique and the activities of nitric oxide synthase (NOS) isoforms were examined by spectroscopy in cortex and hippocampus of neonatal rats at different times after HIBD or sham operation.Results: The expression of ICAM-1 mRNA and protein raised obviously 12h after HIBD , peaked at 24h , and then decreased gradually. There was a remarkable lower expression in CDPC group and simvastatin group compared with HIBD group at 12h, 24h, 48h and 72h. At 7d , there was no significant difference between simvastatin group and sham group ( P>0.05 ); and at 72h, simvastatin downregulated the expression of ICAM-1 mRNA and protein in cortex significantly than citicoline (P<0.05). The activity of inducible NOS increased significantly 12h after HIBD, and peaked at 48h . Simvastatin and citicoline both downregulated remarkably the activity of inducible NOS at 12h, 24h ,48h and 72h, but simvastatin was superior to citicoline. The activity of constitutive NOS rised greatly at 0h after HIBD, then declined slowly and there was no remarkable difference between HIBD group and sham group at 72h. But the activity of constitutive NOS in CDPC group and simvastatin group went up continually after 0h and peaked at 48h.Conclusion:â‘ ICAM-1 is upregulated in neurons following HIBD .â‘¡Both simvastatin and CDPC can relieve the damages of the brain in rats HIBD .â‘¢Intercellular adhesion molecule-1 and nitric oxide synthase may play a role in the pathogenesis of HIBD.â‘£The protective mechanisms of simvastatin and citicoline are associated with their regulations on ICAM-1 and NOS ; and simvastatin is superior to citicoline.