Abstract: Objective To investigate mechanisms of the extracellular signal-regulated kinase signaling pathway, and the protective effect of apoE-mimetic peptide1410 after severe cerebral vasospasm (CVS)in mice. Methods A SAH model was established by endovascular perforation without opening cranium. 134 male ICR mice were randomly divided into four groups: sham operation group, model control group, LY367385 group and apoE group. Ten minutes after SAH, 5μl of LY367385 were microinjected into the lateral cerebral ventricle in LY367385 group. Before 30 min of operation mice were injected with apoE-mimetic peptide1410(0.6 mg/kg)via the tail vein and repeated every 12 hours for three days in apoE group. The neurological behavioral function was evaluated.At different time points (6, 24, 48 hours) after operation, changes in brain tissue were observed with light and electron microscopy. The expression of mGluR1 mRNA was detected using RT-PCR, Western blotting assay was used to examine mGluR1 and p-ERK1/2 expression. The number of apoptotic cells was determined by TUNEL method. Results In model control group, the neurological function scores were significantly lower, and the mGluR1 mRNA, mGluR1, p-ERK1/2 level and the number of apoptosis cells were significantly enhanced. Some neurons displayed histopathologie changes of necrosis, and organelles decreased. Mice treated with LY367385 or apoE-mimetic peptide1410 had reduction in mGluR1 mRNA, mGluR1, ERK1/2 activity, and neuronal apoptosis. apoE-mimetic peptide1410 notably relieved the neurological scores, and improved the ultrastructural changes. Conclusion The increased expression of mGluR1 in hippocampus may induce apoptosis by activation of ERK1/2 signaling after CVS. LY367385 has a good therapeutic effect on

Key words: Cerebral vasospasm, Metabotropic glutamate receptors, Extracellular signal regulated kinase, Immunohistochemistry, Western blotting, TUNEL, Mouse