Abstract
Ischemic stroke presents a major global economic and public health burden. Although recent advances in available endovascular therapies show improved functional outcome, a good number of stroke patients are either ineligible or do not have access to these treatments. Also, robust collateral flow during acute ischemic stroke independently predicts the success of endovascular therapies and the outcome of stroke. Hence, adjunctive therapies for cerebral blood flow (CBF) enhancement are urgently needed. A very clear overview of the pial collaterals and the role of genetics are presented in this review. We review available evidence and advancement for potential therapies aimed at improving CBF during acute ischemic stroke. We identified heme-free soluble guanylate cyclase activators; Sanguinate, remote ischemic perconditioning; Fasudil, S1P agonists; and stimulation of the sphenopalatine ganglion as promising potential CBF-enhancing therapeutics requiring further investigation. Additionally, we outline and discuss the critical steps required to advance research strategies for clinically translatable CBF-enhancing agents in the context of acute ischemic stroke models.