Acute development of collateral circulation and therapeutic prospects in ischemic stroke

Abstract

In acute ischemic stroke, collateral circulation plays an important role in maintaining blood flow to the tissue that is at risk of progressing into ischemia, and in increasing the successful recanalization rate without hemorrhagic transformation. We have reported that well-developed collateral circulation is associated with smaller infarct volume and better long-term neurological outcome, and it disappears promptly once the effective recanalization is achieved. Contrary to the belief that collateral vessels develop over time in chronic stenotic condition, there exists a phenomenon that collateral circulation develops immediately in acute stenosis or occlusion of the arteries and it seems to be triggered by fluid shear stress, which occurs between the territories of stenotic/occluded arteries and those fed by surrounding intact arteries. We believe that this acute development of collateral circulation is a target of novel therapeutics in ischemic stroke and refer our recent attempt in enhancing collateral circulation by modulating sphingosine-1-phosphate receptor 1, which is a known shear-stress mechanosensing protein.

Total Glycosides of Cistanche deserticola Promote Neurological Function Recovery by Inducing Neurovascular Regeneration via Nrf-2/Keap-1 Pathway in MCAO/R Rats

“…Thus, TGs are considered the major active fraction of C. deserticola for neuroprotection, potentially through promoting neural remodeling, angiogenesis and BBB integrity via activating Nrf-2/Keap-1 pathway. Mounting evidence indicates that establishment of effective collateral circulation is significantly important for avoiding the formation of infarction and ischemic penumbra, and is a critical treatment at an early stage of ischemic stroke (ElAli, 2016;Iwasawa et al, 2016). The proliferation of vascular endothelial cells and smooth muscle cells after ischemic infarction determines the establishment of collateral circulation.…”

The Association between FLAIR Vascular Hyperintensity and Stroke Outcome Varies with Time from Onset

“…Within 6 hours of onset or within the time window of reperfusion therapy, FVH might be a marker of leptomeningeal anastomoses that are anatomically present and develop dramatically and rapidly after the onset of acute ischemic stroke. 2,5 The areas with FVH, especially those with FVH-DWI mismatch, represent the brain tissue at risk of infarction, which could be saved by reperfusion therapy to reduce the final lesion volume and improve outcome. 6,9,16,29 This may explain why patients with FVH have better outcomes than those without FVH in this period.…”

“…Some collaterals such as leptomeningeal anastomoses may be anatomically present, though enhanced capacity for cerebral blood flow likely requires time to develop. [1][2][3][4][5] Angiogenesis induced by hypoxia and increased fluid shear stress also requires several days to weeks. 1,2 Furthermore, the incipient development of collaterals does not guarantee their persistence.…”

“…[1][2][3][4][5] Angiogenesis induced by hypoxia and increased fluid shear stress also requires several days to weeks. 1,2 Furthermore, the incipient development of collaterals does not guarantee their persistence. 1 Therefore, the prognostic significance of an observation of the presence of collaterals after ischemic stroke varies with time.…”

Exercise training provides cardioprotection by activating and coupling endothelial nitric oxide synthaseviaa β3-adrenergic receptor-AMP-activated protein kinase signaling pathway

“…Additionally, it is widely accepted that increases in blood flow across the endothelial cell surface are potent stimuli for the production of NO from eNOS 33. Studies using cultured endothelial cells and isolated blood vessels suggest that shear stress induces a signaling cascade involving Akt, PKA and/or AMPK 343536. Importantly, these kinases appear to act independently of each other, suggesting that if one pathway is compromised the other two can still increase NO 34.…”