Transient increase of manganese-superoxide dismutase in remote brain areas after focal photothrombotic cortical lesion.
OBJECTIVE
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.
Bidmon
H J
HJ
Department of Neuroanatomy, Heinrich-Heine-University, Düsseldorf, Germany. hjb@hirn.uni-duesseldorf.de
Kato
K
K
Schleicher
A
A
Witte
O W
OW
Zilles
K
K
D000818:Animals; D000906:Antibodies; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009475:Neurons, Afferent / Q000378:metabolism / Q000473:pathology; D009476:Neurons, Efferent / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012395:Rose Bengal; D013482:Superoxide Dismutase / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D000906:Antibodies; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D005609:Free Radicals; D018696:Neuroprotective Agents; D012395:Rose Bengal; D013482:Superoxide Dismutase