title: Statins and anti-inflammatory therapies for subarachnoid hemorrhage.
abstract: Aneurysmal subarachnoid hemorrhage (SAH) induces a potent inflammatory cascade that contributes to endothelial dysfunction, imbalance of vasoactive substances (excess endothelin, depletion of nitric oxide), and arterial vasospasm. This process results in delayed cerebral ischemia, a major cause of neurologic disability in those surviving the initial hemorrhage. The only therapy shown to be effective in improving neurologic outcomes after SAH is a calcium-channel antagonist, nimodipine (although it achieved this result without reducing vasospasm). A number of novel therapies have been explored to inhibit the development of vasospasm and reduce the burden of ischemia and cerebral infarction. Statins are promising candidates, as they block multiple aspects of the inflammatory pathway that contributes to ischemic brain injury. Early clinical trials have produced conflicting results, however, and the adoption of statins in clinical practice should await the results of larger, more definitive studies. Though endothelin-receptor antagonists showed promise in significantly reducing vasospasm in preliminary trials, their failure to improve clinical outcomes in phase 3 studies has been disappointing, highlighting the complex link between vasospasm and ischemia. Future directions in the quest to improve outcomes of patients with SAH may need to approach ischemia as a multifactorial process with inflammatory, vasoactive, and ionic/metabolic components.
authors.affiliation: Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S. Euclid Ave., St. Louis, MO, 63110, USA, dharr@neuro.wustl.edu.
authors.forename: Rajat
authors.initials: R
authors.lastname: Dhar
authors.forename: Michael
authors.initials: M
authors.lastname: Diringer