Collaterals: Implications in cerebral ischemic diseases and therapeutic interventions

Abstract

Despite the tremendous progress made in the treatment of cerebrovascular occlusive diseases, many patients suffering from ischemic brain injury still experience dismal outcomes. Although rehabilitation contributes to post-stroke functional recovery, there is no doubt that interventions that promote the restoration of blood supply are proven to minimize ischemic injury and improve recovery. In response to the acutely decreased blood perfusion during arterial occlusion, arteriogenesis, the compensation of blood flow through the collateral circulation during arterial obstructive diseases can act not only in a timely fashion but also much more efficiently compared to angiogenesis, the sprouting of new capillaries, and a mechanism occurring in a delayed fashion while increases the total resistance of the vascular bed of the affected territory. Interestingly, despite the vast differences between the two vascular remodeling mechanisms, some crucial growth factors and cytokines involved in angiogenesis are also required for arteriogenesis. Understanding the mechanisms underlying vascular remodeling after ischemic brain injury is a critical step towards the development of effective therapies for ischemic stroke. The present article will discuss our current views in vascular remodeling acutely after brain ischemia, namely arteriogenesis, and some relevant clinical therapies available on the horizon in augmenting collateral flow that hold promise in treating ischemic brain injury. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.

Keywords: Anastomosis; Angiogenesis; Arteriogenesis; Carotid disease; Stroke; Vascular remodeling.

Figure

Type-II diabetes db/db mice exhibit impaired collateral flow recruitment after experimental stroke compared to their normoglycemic control db/+ mice. Retrograde collateral flow dynamics was assessed by Doppler optical coherent tomography (DOCT), a non-invasive high-resolution three-dimensional optical imaging technique for microangiography. Representative DOCT images of db/+ and db/db mice at baseline and immediately after MCAO were shown. The anatomic orientation is labeled with arrows pointing to the lateral (L) and anterior (A) directions. Dotted white lines mark the divide between MCA and ACA territory. White- and black-filled arrows indicate MCA and ACA branches, respectively. The direction of blood flow is color-coded, with the blood flowing towards the scanning probe beam or towards ACA territory coded as red, and the retrograde flow towards proximal MCA as green. Arrowheads indicate the tortuous anastomoses between MCA and ACA. Scale bar: 1 mm.