From the Departments of Neuroanatomy (H.-J.B., A.S., K.Z.) and Neurology
(O.W.W.), Heinrich-Heine-University, Düsseldorf, Germany; and Department
of Biochemistry (K.K.), Aichi Human Service Center, Kamiya, Kasugai, Japan.
Correspondence to Hans-J. Bidmon, Department of Neuroanatomy, Bldg. 22.03.05 Heinrich-Heine-University, PO Box 10 10 07, Moorenstrasse 5, D-40225 Düsseldorf, Germany. E-mail hjb{at}hirn.uni-duesseldorf.de
Background and PurposeFree radicals
including superoxide are responsible for postlesional cytotoxicity. In
contrast to the constitutive CuZnsuperoxide dismutases (SODs),
manganesesuperoxide dismutase (MnSOD) is inducible and has the
potential to protect neurons by its superoxide dismutating activity.
Therefore, we studied the presence and the regional changes in MnSOD
within the brain after focal cortical ischemia.
MethodsFocal cortical photothrombotic lesions were produced in
the hindlimb region of rat brains. Animals were anesthetized
and transcardially perfused with Zamboni's fixative. MnSOD was
immunohistochemically localized using an antiserum against rat-MnSOD.
Changes in MnSOD immunoreactivity were quantified by image
analysis.
ResultsFocal photothrombosis caused a perilesional increase in
MnSOD 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, MnSOD was present in
neurons and astrocytes. Up to day 7, MnSOD increased in the entire
ipsilateral and contralateral cortex but remained higher elevated in
the ipsilateral hippocampus and thalamus. Thereafter, MnSOD decreased
globally but remained elevated in some cortical neurons up to day
60.
ConclusionsThe early transient increase of MnSOD in distinct
brain regions, which are functionally connected via afferents and
efferents, suggests that these regions are affected by the injury. It
suggests that MnSOD protects the cells in these regions from
superoxide-induced damage and therefore may limit the retrograde and
anterograde spread of neurotoxicity.
Department
of Anesthesiology/,
Critical Care Medicine,
The Johns Hopkins University,
School of Medicine,
Baltimore, Maryland
© 1998 American Heart Association, Inc.
Original Contributions
Transient Increase of ManganeseSuperoxide Dismutase in Remote Brain Areas After Focal Photothrombotic Cortical Lesion
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