Vascular Protection Following Cerebral Ischemia and Reperfusion

Abstract

Despite considerable research that has contributed to a better understanding of the pathophysiology of stroke, translation of this knowledge into effective therapies has largely failed. The only effective treatment for ischemic stroke is rapid recanalization of an occluded vessel by dissolving the clot with tissue plasminogen activator (tPA). However, stroke adversely affects vascular function as well that can cause secondary brain injury and limit treatment that depends on a patent vasculature. In middle cerebral arteries (MCA), ischemia/reperfusion (I/R) cause loss of myogenic tone, vascular paralysis, and endothelial dysfunction that can lead to loss of autoregulation. In contrast, brain parenchymal arterioles retain considerable tone during I/R that likely contributes to expansion of the infarct into the penumbra. Microvascular dysregulation also occurs during ischemic stroke that causes edema and hemorrhage, exacerbating the primary insult. Ischemic injury of vasculature is progressive with longer duration of I/R. Early postischemic reperfusion has beneficial effects on stroke outcome but can impair vascular function and exacerbate ischemic injury after longer durations of I/R. This review focuses on current knowledge on the effects of I/R on the structure and function of different vascular segments in the brain and highlight some of the more promising targets for vascular protection.

Brain hemorrhage after endovascular reperfusion therapy of ischemic stroke: a threshold-finding whole-brain perfusion CT study

“…27 Postischemic reperfusion can impair vascular function and exacerbate ischemic injury after longer durations of ischemia and reperfusion. 28 In experimental models of thromboembolic middle cerebral artery occlusion in rats the duration of brain ischemia prior to reperfusion parallels an increased risk and severity of hemorrhagic transformation. Thus, after 6 h of occlusion the risk of PH was significantly increased in comparison with shorter occlusion times (3 h) or permanent occlusion.…”

Protective actions of des-acylated ghrelin on brain injury and blood–brain barrier disruption after stroke in mice

“…Moreover, such mechanisms also contribute to blood-brain barrier (BBB) disruption after ischemia and reperfusion, as well as dysfunction of arteries upstream of the BBB (3,4). There is a growing appreciation of the contribution of these vascular changes to brain injury and edema, and thus the importance of protecting the cerebral endothelium as part of an effective stroke therapy (5).…”

N2 ameliorates neural injury during experimental ischemic stroke via the regulation of thromboxane A2 production

“…PGI 2 possesses the opposite biological activity of TXA 2 . Balanced vascular tension and integration of the endothelium lining under the vascular are essential for normal circulatory function (Ribeiro et al, 2009;Palomares and Cipolla, 2011). BMECs regulate the selective transport and metabolism of substances from blood to the brain and in the opposite direction from the parenchyma back to systemic circulation (Zheng et al, 2003;Cardoso et al, 2010).…”