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

Subarachnoid hemorrhage (SAH) is a common and often devastating occurrence; each year approximately 7-20 of every 100,000 people experience nontraumatic SAH (1-3). Despite considerable advances in diagnostic, surgical, and anesthetic techniques, and advances in perioperative management, the outcome for patients with SAH remains poor, with an overall mortality rate of 25% and significant morbidity among approximately 50% of survivors (1-3). Cerebral vasospasm, which is a major cause of morbidity and mortality after SAH (1-3), is the delayed narrowing of large-capacitance arteries at the base of the brain. Angiographic vasospasm typically develops 3-5 days after SAH and is most severe 7-9 days after SAH (1-3). In approximately half of all cases, a delayed neurologic ischemic deficit occurs, and despite maximal therapy, 15-20% of such patients suffer stroke or die from vasospasm (1-3). Of the patients who survive, vasospasm spontaneously resolves over the course of several days and usually disappears by the end of the second or fourth week (1-3). Recent evidence suggests that hemoglobin-induced (Hb-induced) oxidative stress plays a central role in the pathogenesis of vasospasm after SAH (4). However, the mechanism by which delayed cerebral vasospasm spontaneously resolves has not been sufficiently investigated. Clarification of the intrinsic mechanism of spasmolysis may lead to a novel therapeutic approach. In the present study, we used an improved differential display technique, fluorescent differential display (FDD) (5), to identify differentially expressed genes and to evaluate the functional significance of such genes in the basilar artery with vasospasm.