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Tin Protoporphyrin Provides Protection Following Cerebral Hypoxia-Ischemia: Involvement of Alternative Pathways

Citation

Sutherland, BA and Shaw, OM and Clarkson, AN and Winburn, IC and Errington, AC and Dixon, CL and Lees, G and Sammut, IA and Appleton, I, Tin Protoporphyrin Provides Protection Following Cerebral Hypoxia-Ischemia: Involvement of Alternative Pathways, Journal of neuroscience research, 89 pp. 1284-1294. ISSN 0360-4012 (2011) [Refereed Article]

Copyright Statement

Copyright 2011 Wiley-Liss,

DOI: doi:10.1002/jnr.22661

Abstract

The contribution of heme oxygenase (HO)-linked pathways to neurodegeneration following cerebral hypoxiaischemia (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 1 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.

Item Details

Item Type:Refereed Article
Keywords:heme oxygenase, neurorpotection, nitric oxide synthase, cyclooxygenase, mitochondria
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Medical and Health Sciences
Author:Sutherland, BA (Dr Brad Sutherland)
ID Code:113398
Year Published:2011
Deposited By:Office of the School of Medicine
Deposited On:2016-12-22
Last Modified:2017-05-01
Downloads:0

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