NDLI: Postischemic Infusion of Cu/Zn Superoxide Dismutase or SOD:Tet451 Reduces Cerebral Infarction Following Focal Ischemia/Reperfusion in Rats

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Postischemic Infusion of Cu/Zn Superoxide Dismutase or SOD:Tet451 Reduces Cerebral Infarction Following Focal Ischemia/Reperfusion in Rats

Content Provider	Semantic Scholar
Author	Francis, Jonathan W. Ren, Jingmei Warren, L. Brown, Robert H. Finklestein, Seth P.
Copyright Year	1997
Abstract	Oxygen-free radicals play a major role in neuronal cell injury following cerebral ischemia/reperfusion. The free-radical scavenging enzyme, Cu/Zn superoxide dismutase (SOD-1), ameliorates various types of brain injury resulting from temporary CNS ischemia. We have compared the cerebroprotective properties of human SOD-1 (hSOD-1) with a novel recombinant SOD-1 hybrid protein, SOD:Tet451, composed of hSOD-1 linked to the neuronal binding fragment of tetanus toxin (TTxC). Following 2 h of temporary middle cerebral artery occlusion, rats infused with equivalent activities of either hSOD-1 or SOD:Tet451 for the initial 3 h of reperfusion showed reductions in cerebral infarct volume of 43 and 57%, respectively, compared to saline-treated controls (P < 0.01). Serum hSOD-1 concentrations in rats receiving SOD:Tet451 were seven-fold higher than those in rats receiving the native enzyme. Animals treated with SOD:Tet451 also demonstrated an extended persistence of hSOD-1 in the bloodstream during drug washout as compared to animals given free enzyme. Immunohistochemical examination of brain sections from an SOD:Tet451-treated ischemic rat showed positive immunoreactivity in the ipsilateral cerebral cortex using either anti-TTxC or anti-human SOD-1 antibodies. Our results document that both hSOD-1 and SOD:Tet451 significantly reduce brain infarct volume in a model of transient focal ischemia/reperfusion in rats. Additionally, our findings suggest that the cerebroprotective effects of SOD-1 may be enhanced by neuronal targeting as seen with the hybrid protein SOD:Tet451.
Starting Page	435
Ending Page	443
Page Count	9
File Format	PDF HTM / HTML
DOI	10.1006/exnr.1997.6547
PubMed reference number	9270054
Journal	Medline
Volume Number	146
Alternate Webpage(s)	https://api.elsevier.com/content/article/pii/S001448869796547X
Alternate Webpage(s)	https://www.sciencedirect.com/science/article/pii/S001448869796547X?dgcid=api_sd_search-api-endpoint
Alternate Webpage(s)	https://doi.org/10.1006/exnr.1997.6547
Journal	Experimental Neurology
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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