Neuronal and inducible nitric oxide synthase inhibitor for cerebral protection during deep hypothermic circulatory arrest in porcine hippocampus.

Neurological and neuropsychological deficits remain common following cardiovascular surgery in infants, yet the mechanisms underlying neuronal injury during deep hypothermic circulatory arrest (DHCA) are not fully understood. Our previous study demonstrated that inhaled nitric oxide (NO) attenuates DHCA-induced microglial activation and neurodegeneration. In this study, we investigated whether targeted inhibition of nitric oxide synthase (NOS) could reduce brain damage following DHCA. Based on previously published data, we used 2-iminobiotin, a selective inhibitor of both neuronal NOS (nNOS) and inducible NOS (iNOS). Juvenile piglets (∼7 wk old) underwent DHCA (cooled to 18°C) for 30 min, followed by rewarming either with or without a NOS inhibitor. Neuroinflammation and neuronal injury were assessed histologically in the hippocampus. TUNEL staining revealed that the NOS inhibitor (TUNEL-positive cells; median 1.3%) significantly alleviated neuronal damage compared with the nontreatment group (median 6.7%). NOS inhibitor also reduced the microglia activities related to the cerebral neuroinflammatory reaction after DHCA. NOS inhibition reduces neuronal degeneration and microglial activation in the hippocampus following DHCA. These findings suggest that the NOS inhibitor reduces neuronal degeneration by ameliorating inflammation.NEW & NOTEWORTHY DHCA demonstrates strongly activated microglia and neuronal damage in the hippocampus. A selective inhibitor of both nNOS and iNOS can reduce neuronal damage by ameliorating neuroinflammation.