Therapeutic Induction of Collateral Flow.

Therapeutic induction of collateral flow as a means to salvage tissue and improve outcome from acute ischemic stroke is a promising approach in the era in which endovascular therapy is no longer time-dependent but collateral-dependent. The importance of collateral flow enhancement as a therapeutic for acute ischemic stroke extends beyond those patients with large amounts of salvageable tissue. It also has the potential to extend the time window for reperfusion therapies in patients who are ineligible for endovascular thrombectomy. In addition, collateral enhancement may be an important adjuvant to neuroprotective agents by providing a more robust vascular route for which treatments can gain access to at risk tissue. However, our understanding of collateral hemodynamics, including under comorbid conditions that are highly prevalent in the stroke population, has hindered the efficacy of collateral flow augmentation for improving stroke outcome in the clinical setting. This review will discuss our current understanding of pial collateral function and hemodynamics, including vasoactivity that is critical for enhancing penumbral perfusion. In addition, mechanisms by which collateral flow can be increased during acute ischemic stroke to limit ischemic injury, that may be different depending on the state of the brain and vasculature prior to stroke, will also be reviewed.