The role of sex as a biological variable in neurocritical care: Fundamentals of cerebrovascular physiology with clinical implications.

Ischemic stroke, intracerebral hemorrhage (ICH), aneurysmal subarachnoid hemorrhage (aSAH), global hypoxic ischemic brain injury following cardiac arrest (HIBI), and traumatic brain injury (TBI) present clinical pathologies that share brain ischemia as a primary or secondary consequence of their respective pathophysiology. Recently, sex-as a biological variable-has received attention for its clear implications in differences in injury pathophysiology, diagnosis, and management. Due to historical, social, and gender biases, females have been excluded from physiology-based research and clinical trials, resulting in limited insight into female physiology and poor translation of current diagnostics and therapies to females. The role of sex-specific hormones has been implicated in a host of sex differences following cerebrovascular injury and the ensuing clinical outcomes. Therefore, this review aims to provide a contemporary overview on the role of biological sex and sex hormones in the underlying physiology, mechanisms, and outcomes of selected cerebrovascular injuries. First, we identify sex-based differences in clinical outcomes in ischemic stroke, ICH, aSAH, HIBI, and TBI. Second, we discuss the impact of biological sex and sex hormones on the fundamentals of cerebrovascular physiology. Finally, related mechanisms of sex-based differences in injury pathophysiology are explored to identify potential therapeutic avenues for future research.