Transient Increase of Manganese–Superoxide Dismutase in Remote Brain Areas After Focal Photothrombotic Cortical Lesion

Abstract

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 these regions from superoxide-induced damage and therefore may limit the retrograde and anterograde spread of neurotoxicity. (Stroke. 1998;29:203-211.)

Secondary Neurodegeneration in Remote Regions After Focal Cerebral Infarction

“…Increased immunoreactivity of manganese-superoxide dismutase and expression of damage-induced neuronal endopeptidase mRNA was observed in the ipsilateral thalamus after MCA occlusion in rats. 42,43 Superoxide dismutases are known to effectively scavenge superoxide radicals and protect neurons from oxidative damage, and damage-induced neuronal endopeptidase can be upregulated in response to neuronal insult and activate superoxide dismutases. Therefore, the elevation of manganese-superoxide dismutase and damage-induced neuronal endopeptidase may reflect increased oxidative stress in the ipsilateral thalamus.…”

Novel Brain Ischemic Change on MRI

“…18 -21 The previous studies revealed that neurons and/or glial cells immunoreactive to Mn-SOD increased in the boundary zone of infarction in the rat striatum after 60 minutes of MCAO, 19 in the gerbil hippocampus after 2 minutes of forebrain ischemia, 20 and in remote brain areas after focal cortical ischemia. 21 On the other hand, Kondo et al 22 reported that iron accumulated in the hippocampal CA1 region, layers III-V of the parietal cortex, and frontocortical layer V in rats after 30 minutes of forebrain ischemia.…”

Regional distribution of manganese superoxide dismutase 2 (Mn SOD2) expression in rodent and primate spiral ganglion cells

“…After deparaffinization, sections were incubated overnight with primary polyclonal antibody raised to full length rat SOD2 protein (Abcam Inc., ab13534) at 1:1000 dilution. This antibody has a broad spectrum of species reactivity (Drosophila and vertebrate) and its specificity has been confirmed by western blotting at 1/2000 dilution to a single band (Saha and Pahan, 2007;Bidmon et al, 1998;Liu et al, 1993). A biotinylated secondary anti-rabbit antibody and standard ABC-peroxidase reagents (Vector Laboratories) were applied.…”