Cerebral autoregulation, spreading depolarization, and implications for targeted therapy in brain injury and ischemia

Cerebral autoregulation is an intrinsic myogenic response of cerebral vasculature that allows for preservation of stable cerebral blood flow levels in response to changing systemic blood pressure. It is effective across a broad range of blood pressure levels through precapillary vasoconstriction and dilation. Autoregulation is difficult to directly measure and methods to indirectly ascertain cerebral autoregulation status inherently require certain assumptions. Patients with impaired cerebral autoregulation may be at risk of brain ischemia. One of the central mechanisms of ischemia in patients with metabolically compromised states is likely the triggering of spreading depolarization (SD) events and ultimately, terminal (or anoxic) depolarization. Cerebral autoregulation and SD are therefore linked when considering the risk of ischemia. In this scoping review, we will discuss the range of methods to measure cerebral autoregulation, their theoretical strengths and weaknesses, and the available clinical evidence to support their utility. We will then discuss the emerging link between impaired cerebral autoregulation and the occurrence of SD events. Such an approach offers the opportunity to better understand an individual patient's physiology and provide targeted treatments.