title: Effects of cold injury-induced trauma in manganese superoxide dismutase-deficient mice.
abstract: Manganese superoxide dismutase (Mn-SOD, SOD2) is an inducible antioxidant localized to the mitochondria, which have been shown to be both the sites of superoxide anion (O(2)*-)) production and the target of free radical attacks. Knock-out mice with targeted disruption of Sod2 (SOD2-KO) are more susceptible to ischemic damage than their wild-type (WT) counterparts, showing increased loss of mitochondrial cytochrome c after trauma, but less apoptotic cell death in the first 24 h following controlled cortical injury. In this study, we sought to investigate whether oxidative stress plays a significant role in the development of secondary brain damage following cold injury-induced brain trauma (CIBT), a model of vasogenic edema. We first measured the levels of O(2)(*-) production 2 h after CIBT by means of in situ hydroethidine oxidation. We then examined lesion size, brain swelling, apoptosis by morphology and TUNEL-staining, neutrophil infiltration, and hemorrhage rates in both SOD2-KO and WT mice at 1, 3, and 7 days post-CIBT. We found no significant differences between SOD2-KO and WT littermates in any of the paradigms or endpoints studied. There was, however, a significant increase in hemorrhagic transformations in all animals that paralleled a robust inflammatory response at 3 days post insult compared with the 24-h endpoint. In the CIBT model used in this study, a 50% reduction in SOD2 activity did not appear to alter the injury response, suggesting that accumulation of free radicals does not play a significant role in secondary brain damage as previously thought with this particular model.
authors.affiliation: Department of Neurosurgery, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Grzeschik
authors.forename: Carolina M
authors.initials: CM
authors.lastname: Maier
authors.forename: Pak H
authors.initials: PH
authors.lastname: Chan
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D003080:Cold Temperature / Q000009:adverse effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2