Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats
Hidenori Suzuki, … , Shiro Waga, Toshio Tanaka
Hidenori Suzuki, … , Shiro Waga, Toshio Tanaka
Published July 1, 1999
Citation Information: J Clin Invest. 1999;104(1):59-66. https://doi.org/10.1172/JCI5357.
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Article

Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats

Abstract

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.

Authors

Hidenori Suzuki, Kenji Kanamaru, Hiroshi Tsunoda, Hiroyasu Inada, Minoru Kuroki, Hong Sun, Shiro Waga, Toshio Tanaka

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(a) In the 1-hemorrhage rats, the HO-1 mRNA levels in the basilar arteri...
(a) In the 1-hemorrhage rats, the HO-1 mRNA levels in the basilar arteries after the treatment with antisense HO-1 ODN (circles, n = 3), sense HO-1 ODN (squares, n = 3), or scrambled ODN (triangles, n = 3) were determined using real-time RT-PCR analysis and were expressed as a ratio of HO-1 mRNA to HO-2 mRNA. Significantly different from the baseline values on day 0 (aP < 0.05, bP < 0.025, cP < 0.01). Significantly different from the values for the antisense HO-1 ODN treatment (dP < 0.05, eP < 0.025, fP < 0.01, gP < 0.005). (b) Competitive RT-PCR analysis of HO-1 and HO-2 mRNA in the basilar arteries on day 1 after the injection of blood. Antisense HO-1 ODN prevented the induction of HO-1 mRNA but did not affect HO-2 mRNA levels. (c) The basilar arteries on day 1 after the injection of blood were also analyzed by electrophoresis on a 12.5% SDS-polyacrylamide gel, followed by Coomassie staining (top) or Western blotting with anti–HO-1 antibodies (bottom). Antisense HO-1 ODN prevented the induction of HO-1 protein.