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.
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA 15232, USA.
Mark E
ME
Bernard
Hyun
H
Kim
Jean-Claude
JC
Rwigema
Michael W
MW
Epperly
Eric E
EE
Kelley
Geoffery H
GH
Murdoch
Tracy
T
Dixon
Hong
H
Wang
Joel S
JS
Greenberger
D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D004947:Esophagus / Q000201:enzymology / Q000294:innervation* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000502:physiology*; D011839:Radiation, Ionizing; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012640:Seizures / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D014630:Vagus Nerve / Q000503:physiopathology*; D014916:Whole-Body Irradiation
D011994:Recombinant Proteins; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse