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

OBJECTIVE

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).

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 wild-type 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.

CONCLUSIONS

NOS1(-/-) mice represent a model system for dissecting the developmental abnormalities leading to esophageal-mediated TBI-induced seizures.