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Tin protoporphyrin provides protection following cerebral hypoxia‐ischemia: Involvement of alternative pathways
Author(s) -
Sutherland Brad A.,
Shaw Odette M.,
Clarkson Andrew N.,
Winburn Ian C.,
Errington Adam C.,
Dixon Christine L.,
Lees George,
Sammut Ivan A.,
Appleton Ian
Publication year - 2011
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22661
Subject(s) - heme oxygenase , chemistry , pharmacology , nitric oxide , nitric oxide synthase , saline , ischemia , heme , biochemistry , medicine , endocrinology , enzyme , organic chemistry
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.