About 30,000 North Americans have rupture of an intracranial aneurysm each year. Because aneurysmal rupture, among all forms of intracranial bleeding, almost uniquely deposits a large volume of blood clot on the adventitial side of the basal conducting arteries, it is frequently the cause of a delayed onset, long-lasting arterial constriction known as vasospasm. Vasospasm can be so severe that the vessels may actually be occluded and distal ischemia can result with attendant delayed infarction - the second stroke. About two-thirds of ruptured aneurysm patients will show moderate to severe degrees of angiographic vasospasm if subjected to angiography a week or so after the initial hemorrhage. About half of these patients will develop clinical signs of delayed ischemia. The death rate from this phenomenon has fallen steadily in recent years with the widespread avoidance of dehydration and antifibrinolytic agents. In addition, calcium antagonists, hypertension and hypervolemia may have exerted a beneficial effect. Currently, however, about 15% of patients will still die or be severely damaged by vasospasm. Evidence of ischemic cerebral infarction is noted in about 30% of the fatal cases of aneurysmal ruptures if they survive past the initial few days. Our long-term objectives are: (1) prevention of vasospasm after subarachnoid hemorrhage; (2) the successful treatment of established vasospasm.
The specific aims of the project are to determine: (1) time course of cytoskeletal changes in arterial walls of cerebral arteries after subarachnoid hemorrhage in monkeys; (2) pathogenesis and prevention of oxyhemoglobin-induced cerebral vasospasm in monkeys; (3) biochemical changes in arterial vessel wall as vasospasm develops and abates; (4) time course of intracellular free calcium concentration changes in cultured vascular smooth muscle cells following prolonged exposure to oxyhemoglobin and if the mechanism of calcium entry is sensitive to normal antagonists of calcium channels; (5) role of activation of protein kinase C in production of cerebrovascular spasm; (6) the source of increased intracellular calcium correlated with damage by oxyhemoglobin; (7) if free radicals damage isolated cerebrovascular smooth muscle cells primarily from the inside or outside; (8) whether free radicals damage lipid components of surface membrane or ion channels; (9) if transluminal balloon dilatation of spastic primate cerebral arteries results in immediate and enduring improvement in vessel caliber and whether there is any adverse structural change in the arterial wall; (10) if intrathecal urokinase can prevent chronic cerebral vasospasm in a primate model.
| Jahromi, Babak S; Aihara, Yasuo; Ai, Jinglu et al. (2008) Temporal profile of potassium channel dysfunction in cerebrovascular smooth muscle after experimental subarachnoid haemorrhage. Neurosci Lett 440:81-6 |
| Aihara, Yasuo; Jahromi, Babak S; Yassari, Reza et al. (2008) Induction of housekeeping gene expression after subarachnoid hemorrhage in dogs. J Neurosci Methods 172:1-7 |
| Sabri, Mohammed; Kawashima, Ayako; Ai, Jinglu et al. (2008) Neuronal and astrocytic apoptosis after subarachnoid hemorrhage: a possible cause for poor prognosis. Brain Res 1238:163-71 |
| Jahromi, Babak S; Aihara, Yasuo; Ai, Jinglu et al. (2008) Voltage-gated K+ channel dysfunction in myocytes from a dog model of subarachnoid hemorrhage. J Cereb Blood Flow Metab 28:797-811 |
| Xie, An; Aihara, Yasuo; Bouryi, Vitali A et al. (2007) Novel mechanism of endothelin-1-induced vasospasm after subarachnoid hemorrhage. J Cereb Blood Flow Metab 27:1692-701 |
| Nikitina, Elena; Zhang, Zhen-Du; Kawashima, Ayako et al. (2007) Voltage-dependent calcium channels of dog basilar artery. J Physiol 580:523-41 |
| Fergusen, Sherise; Macdonald, R Loch (2007) Predictors of cerebral infarction in patients with aneurysmal subarachnoid hemorrhage. Neurosurgery 60:658-67;discussion 667 |
| Rosen, David S; Amidei, Chris; Tolentino, Jocelyn et al. (2007) Subarachnoid clot volume correlates with age, neurological grade, and blood pressure. Neurosurgery 60:259-66;discussion 266-7 |
| Rosengart, Axel J; Schultheiss, Kim E; Tolentino, Jocelyn et al. (2007) Prognostic factors for outcome in patients with aneurysmal subarachnoid hemorrhage. Stroke 38:2315-21 |
| Zhang, Zhen-Du; Macdonald, R Loch (2006) Contribution of the remodeling response to cerebral vasospasm. Neurol Res 28:713-20 |
Showing the most recent 10 out of 67 publications
