Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats.
Delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) causes cerebral ischemia and infarction. To date, the pathogenesis and gene expression associated with vasospasm remain poorly understood. The present study used fluorescent differential display to identify differentially expressed genes in a rat model of SAH. By using quantitative RT-PCR, we found that heme oxygenase-1 (HO-1) mRNA was prominently induced in the basilar artery and modestly in brain tissue in a rat vasospasm model. A significant correlation was observed between the degree of vasospasm and HO-1 mRNA levels in the basilar arteries exhibiting vasospasm. Intracisternal injection of antisense HO-1 oligodeoxynucleotide (ODN) significantly delayed the clearance of oxyhemoglobin and deoxyhemoglobin from the subarachnoid space and aggravated angiographic vasospasm. Antisense HO-1 ODN inhibited HO-1 induction in the basilar arteries but not in the whole brain tissue. This phenomenon was not observed in the nontreated, sense HO-1 ODN-treated, or scrambled ODN-treated arteries. We report the protective effects of HO-1 gene induction in cerebral vasospasm after SAH, a finding that should provide a novel therapeutic approach for cerebral vasospasm.
Department of Molecular and Cellular Pharmacology, Mie University School of Medicine, Mie 514-8507, Japan.
H
H
Suzuki
K
K
Kanamaru
H
H
Tsunoda
H
H
Inada
M
M
Kuroki
H
H
Sun
S
S
Waga
T
T
Tanaka
D000818:Animals; D001488:Basilar Artery / Q000201:enzymology; D001921:Brain / Q000201:enzymology*; D002533:Cerebral Angiography; D004790:Enzyme Induction; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D006454:Hemoglobins / Q000378:metabolism; D007278:Injections, Spinal; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D018384:Oxidative Stress; D010108:Oxyhemoglobins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013345:Subarachnoid Hemorrhage / Q000150:complications; D013382:Subtraction Technique
D006454:Hemoglobins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D010108:Oxyhemoglobins; D012333:RNA, Messenger; C100003:deoxyhemoglobin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1