Aneurysmal subarachnoid hemorrhage (aSAH) is a sudden life-threatening bleeding occurring in the subarachnoid space (i.e. between two layers of the protective membranes that surround the brain). It is caused by the rupture of an aneurysm - a weak bulging spot on the wall of a brain artery - that causes blood to escape and accumulate in the space around the brain. To stop the bleeding, endovascular coiling or microsurgical clipping is required.
Aneurysmal SAH is estimated to affect 30,000 patients in the US each year. The mortality rate for patients suffering from aSAH is high, and among those who survive, long-term symptoms such as physical disabilities are common, making them entirely dependent upon relatives or caregivers.
In about half of aSAH patients, after a few days of improvement, a worsening of their condition may occur due to a cerebral vasospasm (constriction of intracerebral arteries), which is at least in part explained by a release of endothelin subsequently to the bleeding event. Cerebral vasospasm diminishes blood flow to the brain and contributes to the severity of brain damage and the poor long-term outcomes associated with aSAH.
Currently, rescue invasive, intra-arterial intervention is used to treat cerebral vasospasm. This therapy is associated with medical risk and often requires repeated procedures. There is no effective pharmacotherapy available for the prevention or the treatment of cerebral vasospasm and its severe complications.