Role of the esophageal vagus neural pathway in ionizing irradiation-induced seizures in nitric oxide synthase-1 homologous recombinant negative NOS1 ^-/- mice

Aim: We sought to define the mechanism of total body irradiation (TBI)-induced seizures in NOS1^-/- mice and amelioration by intra-esophageal manganese superoxide dismutase-plasmid liposomes (MnSOD-PL). Materials and Methods: We evaluated the role of vagus nerve pathways in irradiation-induced seizures using biochemical, physiologic, and histopathologic techniques. Results: Heterozygous NOS1^+/- mice demonstrated radioresistance similar to wildtype C57BL/6NHsd mice (p=0.9269). Irradiation-induced lipid peroxidation in fetal brain cultures from NOS1 ^-/- or wild-type mice was reduced by MnSOD-PL. Right-sided vagotomy did not alter the TBI radiation response of wild-type or reverse the radiosensitivity of NOS1^-/- mice. Excised esophagus from irradiated NOS1^-/- mice demonstrated an increased histopathologic inflammatory response compared to C57BL/6NHsd mice. Conclusion: NOS1^-/- mice represent a model system for dissecting the developmental abnormalities leading to esophageal-mediated TBI-induced seizures.