[The role of NO resulted from neuronal nitric oxide synthase in the metabotropic glutamate receptor2/3 mediated-brain ischemic tolerance].

AIM

To explore the role of nitric oxide (NO) resulted from nNOS in the mGluR2/3 mediated-brain ischemic tolerance induced by cerebral ischemic preconditioning (CIP), the present study is undertaken to observe the influences of alpha-methyl-(4-tetrazolyl-phenyl) glycine (MTPG), an antagonist of mGluR2/3, on the expression of nNOS during the induction of the brain ischemic tolerance based on confirming the blocking effect of MTPG on the induction of the tolerance.

METHODS

Thirty-six Sprague-Dawley rats, whose vertebral arteries were permanently occluded, were randomly divided into sham, CIP, ischemic insult, CIP+ ischemic insult, MTPG+ CIP and MTPG+ CIP+ ischemic insult groups. Thionin staining and immunohistochemistry were used for neuropathological evaluation and assay of nNOS expression in the hippocampal CA1 subregion of the rats.

RESULTS

The expression of nNOS showed moderate and extreme up-regulation in the CIP and ischemia groups, respectively, compared to the sham group. The preceded CIP blocked in certain extent the extreme up-regulation of nNOS induced by brain ischemia in CIP + ischemia group. Administration of MTPG via lateral cerebral ventricle 20 min before CIP blocked the up-regulation of nNOS induced by CIP, but had no influence on the pyramidal neuronal survival. While in the MTPG+ CIP+ ischemic insult group, the expression of nNOS was stronger than that in the MTPG + CIP group, and the up-regulation was accompanied with obvious delayed neuronal death. Discussion concerned illustrated that the relative intensive up-regulation of nNOS in this group might be attributed to brain ischemia other than MTPG.

CONCLUSION

NO resulted from nNOS participated the induction of mGluR2/3 mediated-brain ischemic tolerance as a downstream molecule of activation of mGluR2/3 during CIP.