Neuronal nitric oxide synthase inhibition reduces brain damage by promoting collateral recruitment in a cerebral hypoxia-ischemia mice model.

OBJECTIVE: The collateral circulation development is considered as a compensatory inherent mechanism to restore damaged blood perfusion after ischemia. We aimed to detect the collateral flow and the mean blood-flow velocities (mBFVs) level in the basilar trunk during or after cerebral hypoxia-ischemia in the mice brain and explore the effect of neuronal nitric oxide synthase (nNOS) inhibition on the collateral flow. MATERIALS AND METHODS: C57BL/6J mice and the nNOS knockout (KO) mice were randomly divided into a sham-operated group (control) and the hypoxia-ischemia (HI) groups that were treated with the phosphate buffered solution (PBS) control or 7-nitroindazole (7-NI). Cortexes were harvested after the HI treatment for analysis of nNOS expression using Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Ultrasound imaging experiments were performed to detect the collateral flow and the mBFVs level in the basilar trunk. RESULTS: After cerebral HI, the cortical nNOS mRNA and protein levels increased markedly compared with the sham-operated control mice. Besides, 7-NI treatment had no effect on the blood flow in the sham-operated control mice. What's more, either the 7-NI pretreatment or the nNOS gene knockdown before the HI procedure could attenuate the brain injury by the increased collateral flow and the decreased mBFVs level in the basilar trunk. CONCLUSIONS: nNOS inhibition protected hypoxic- ischemic-induced mice brain damage by the increased collateral flow and the decreased mBFVs level in the basilar trunk. Therefore, the 7-NI administration may have potential utility for the treatment of HI injury in human beings.