Induction of heme oxygenase protein protects neurons in cortex and striatum, but not in hippocampus, against transient forebrain ischemia.
To clarify whether heme oxygenase-1 (HO-1) protein plays a protective role against cerebral ischemia, we investigated the effects of an HO inhibitor (tin mesoporphyrin IX [SnMP] three doses of 30 micromol/kg, intraperitoneally) and an HO inducer (hemin, three doses of 30 micromol/kg, intraperitoneally) on the pathologic outcome and on the immunohistochemical reaction for HO-1 after 20-minute transient forebrain ischemia followed by 3-day reperfusion in rats. Hemin significantly increased viable neurons in the cortex (compared to the SnMP-treated group, P < .05) and striatum (compared to the saline-treated group at P < .01 and SnMP-treated group at P < .05), and intense HO-1 immunoreactivity was observed in cortex and striatum, whereas the administration of SnMP tended to decrease viable neurons in the parietal cortex. In contrast, neither hemin nor SnMP affected the pathologic outcome in the CA1 and CA3 hippocampi, in which HO-1 immunoreactivity was weak. These results suggest that induction of HO-1 protein may contribute to cellular defense against ischemic damage in brain regions where potential ability to synthesize HO-1 is retained in ischemia.
Takizawa
S
S
Department of Neurology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Hirabayashi
H
H
Matsushima
K
K
Tokuoka
K
K
Shinohara
Y
Y
D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology*; D003342:Corpus Striatum / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006427:Hemin / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology*; D007274:Injections, Intraperitoneal; D002546:Ischemic Attack, Transient / Q000201:enzymology* / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D008652:Mesoporphyrins / Q000008:administration & dosage; D016548:Prosencephalon / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D008652:Mesoporphyrins; C031468:mesoporphyrin IX; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing)