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Tin protoporphyrin provides protection following cerebral hypoxia-ischemia: Involvement of alternative pathways.
MedLine Citation:
PMID:  21538467     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The contribution of heme oxygenase (HO)-linked pathways to neurodegeneration following cerebral hypoxia-ischemia (HI) remains unclear. We investigated whether HO modulators affected HI-induced brain damage and explored potential mechanisms involved. HI was induced in 26-day-old male Wistar rats by left common carotid artery ligation, followed by exposure to a humidified atmosphere of 8% oxygen for 1 hr. Tin protoporphyrin (SnPP; an HO inhibitor), ferriprotoporphyrin (FePP; an HO inducer), or saline was administered intraperitoneally once daily from 1 day prior to HI until sacrifice at 3 days post-HI. SnPP reduced (P < 0.05) infarct volume compared with saline-treated animals, but FePP had no effect on brain injury. SnPP did not significantly inhibit HO activity at 3 days post-HI, but SnPP increased (P < 0.001) total nitric oxide synthase (NOS) activity compared with HI + saline. Both inducible NOS and cyclooxygenase activities were attenuated (P < 0.05) by SnPP, whereas mitochondrial complex I and V activities were augmented (P < 0.05) by SnPP. SnPP had no effect on NMDA receptor currents. Overall, like other HO inhibitors, SnPP produced many nonselective effects, such as attenuation of inflammatory enzymes and increased mitochondrial respiratory function, which were associated with a protective response 3 days post-HI. © 2011 Wiley-Liss, Inc.
Authors:
Brad A Sutherland; Odette M Shaw; Andrew N Clarkson; Ian C Winburn; Adam C Errington; Christine L Dixon; George Lees; Ivan A Sammut; Ian Appleton
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-2
Journal Detail:
Title:  Journal of neuroscience research     Volume:  -     ISSN:  1097-4547     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Affiliation:
Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand. brad.sutherland@ndm.ox.ac.uk.
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