Abstract
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 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. Conclusion: NOS1−/− mice represent a model system for dissecting the developmental abnormalities leading to esophageal-mediated TBI-induced seizures.
- Received June 17, 2011.
- Revision received August 5, 2011.
- Accepted August 8, 2011.
- Copyright © 2011 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved