Transient increase of manganese-superoxide dismutase in remote brain areas after focal photothrombotic cortical lesion

Background and Purpose-Free radicals including superoxide are responsible For postlesional cytotoxicity, In contrast to the constitutive CuZn-superoxide dismutases (SODs), manganese-superoxide dismutase (Mn-SOD) is inducible and has the potential to protect neurons by its superoxide dismutating activity, Therefore, we studied the presence and the regional changes in Mn-SOD within the brain after focal cortical ischemia. Methods-Focal cortical photothrombotic lesions were produced in the hindlimb region of rat brains. Animals were anesthetized and transcardially perfused with Zamboni's fixative. Mn-SOD was immunohistochemically localized using an antiserum against rat-Mn-SOD. Changes in Mn-SOD immunoreactivity were quantified by image analysis, Results-Focal photothrombosis caused a perilesional increase in Mn-SOD after 24 hours, followed by a further significant increase at 48 hours in perilesional cortex, ipsilateral corpus callosum, hippocampus, and thalamus, as well, as in a homotopic cortical area within the nonlesioned hemisphere. At day 2, Mn-SOD was present in neurons and astrocytes. Up to day 7, Mn-SOD increased in the entire ipsilateral and contralateral cortex but remained higher elevated in the ipsilateral hippocampus and thalamus. Thereafter, Mn-SOD decreased globally but remained elevated in some cortical neurons up to day 60. Conclusions-The early transient increase of Mn-SOD in distinct brain regions, which are functionally connected via afferents and efferents, suggests that these regions are affected by the injury, It suggests that Mn-SOD protects the cells in bb these regions from superoxide-induced damage and therefore may limit the retrograde and anterograde spread of neurotoxicity.