Subarachnoid hemorrhage and inflammation: bench to bedside and back

Abstract

Subarachnoid hemorrhage (SAH) is a devastating and complicated disease. The development of therapeutic interventions has been hampered by a poor understanding of the three components of the disease pathology in SAH: aneurysm rupture, cerebral edema, and vasospasm. The role of inflammation in the pathology of subarachnoid hemorrhage will be reviewed. The events leading up to aneurysm rupture are heralded by degradation of the endothelial cell layer integrity and inflammatory cell infiltration into the wall of the aneurysm. This is associated with release of active agents that can digest the basement membrane and may cause rupture. After rupture, cytokine release by mononuclear leukocytes is associated with early edema. Vasospasm is a complicated process that includes arterial wall thickening and vasoconstriction. Evidence supports the role of inflammation in free radical formation and in perturbations in nitric oxide and endothelin-1 levels that are important mediators of the vasoconstriction in vasospasm. Targeting the inflammatory mediators associated with the three prominent events in SAH is a promising strategy for reducing the mortality and morbidity in these patients. More study is needed to determine which specific effectors in the inflammatory cascade may serve as targets for intervention.