Cerebral vasospasm (CVS) is a potentially lethal complication of aneurysmal subarachnoid hemorrhage (aSAH). Recently, the symptomatic presentation of CVS has been termed delayed cerebral ischemia (DCI), occurring as early as 3-4 days after the sentinel bleed. For the past 5-6 decades, scientific research has promulgated the theory that cerebral vasospasm plays a primary role in the pathology of DCI and subsequently delayed ischemic neurological decline (DIND). Approximately 70% of patients develop CVS after aSAH with 50% long-term morbidity rates. The exact etiology of CVS is unknown; however, a well-described theory involves an antecedent inflammatory cascade with alterations of intracellular calcium dynamics and nitric oxide fluxes, though the intricacies of this inflammatory theory are currently unknown. Consequently, there have been few advances in the clinical treatment of this patient cohort, and morbidity remains high. Identification of intermediaries in the inflammatory cascade can provide insight into newer clinical interventions in the prevention and management of cerebral vasospasm and will hopefully prevent neurological decline. In this review, we discuss current theories implicating the inflammatory cascade in the development of CVS and potential treatment targets. 1. Introduction Subarachnoid hemorrhage (SAH) is a devastating neurological insult that causes significant morbidity and mortality [1]. One of the greatest sources of this morbidity and mortality is cerebral vasospasm (CVS), leading to delayed cerebral ischemia (DCI) [2]. While angiographic vasospasm is thought to occur in approximately 70% of patients after aSAH, only 25% develop symptomatic CVS [3, 4]. Morbidity remains high despite years of clinical and basic science research done on the topic, with approximately 50% infarction rates in affected patients [5, 6]. An antecedent inflammatory cascade is one of the many etiologies thought to be responsible for the development of CVS. Experimental studies have shown involvement of cytokines, cell adhesion molecules, and leukocytes, and early clinical studies have attempted to inhibit components of the inflammatory cascade to mitigate CVS [7–19]. Additionally, endothelin receptor activation, nitric oxide inhibition, thromboxane receptor modification, and many cell signaling cascades are thought to play an integral role in the development of this pathology [20–27]. Currently, the primary treatment for this patient population involves hemodynamic augmentation and medically or surgically mediated intra-arterial vasodilation. These
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