In recent decades, a large body of research has focused on the role of nitric oxide (NO) in the development of cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH). Literature searches were therefore conducted regarding the role of NO in cerebral vasospasm, specifically focusing on NO donors, reactive nitrogen species, and peroxynitrite in manifestation of vasospasm. Based off the assessment of available evidence, two competing theories are reviewed regarding the role of NO in vasospasm. One school of thought describes a deficiency in NO due to scavenging by hemoglobin in the cisternal space, leading to an NO signaling deficit and vasospastic collapse. A second hypothesis focuses on the dysfunction of nitric oxide synthase, an enzyme that synthesizes NO, and subsequent generation of reactive nitrogen species. Both theories have strong experimental evidence behind them and hold promise for translation into clinical practice. Furthermore, NO donors show definitive promise for preventing vasospasm at the angiographic and clinical level. However, NO augmentation may also cause systemic hypotension and worsen vasospasm due to oxidative distress. Recent evidence indicates that targeting NOS dysfunction, for example, through erythropoietin or statin administration, also shows promise at preventing vasospasm and neurotoxicity. Ultimately, the role of NO in neurovascular disease is complex. Neither of these theories is mutually exclusive, and both should be considered for future research directions and treatment strategies. 1. Introduction Subarachnoid hemorrhage (SAH) is a form of stroke that affects 28,000 individuals in North America each year [1]. A frequent cause of SAH is the rupture of an intracranial aneurysm, leading to extravasation of blood into the subarachnoid space. While aneurysmal SAH accounts for only 7% of all cerebrovascular accidents (CVAs), those that suffer SAH have an average age of 51 years, significantly younger than those with a thromboembolic or hemorrhagic stroke [1]. Due to the young age of these patients, they have great potential to return to their premorbid state and level of productivity, with successful intervention. However, even with endovascular or surgical repair of the offending aneurysm, those that survive the initial insult can still accumulate additional neurologic defects in the days and weeks post-hemorrhage. Enormous efforts to understand and prevent additional mortality following SAH led to the discovery of the phenomenon known as cerebral vasospasm (CV) [1]. CV refers to the constriction of smooth muscle
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