Abstract
Enhancing the collateral blood supply during the acute phase of cerebral ischemia may limit both the extension of the core infarct, by rescuing the penumbra area, and the degree of disability. Many imaging techniques have been applied to rodents in preclinical studies, to evaluate the magnitude of collateral blood flow and the time course of responses during the early phase of ischemic stroke. The collateral supply follows several different routes at the base of the brain (the circle of Willis) and its surface (leptomeningeal or pial arteries), corresponding to the proximal and distal collateral pathways, respectively. In this review, we describe and illustrate the cerebral collateral systems and their modifications following pre-Willis or post-Willis occlusion in rodents. We also review the potential pharmaceutical agents for stimulating the collateral blood supply tested to date. The time taken to establish a collateral blood flow supply through the leptomeningeal anastomoses differs between young and adult animals and between different species and genetic backgrounds. Caution is required when transposing preclinical findings to humans, and clinical trials must be performed to check the added value of pharmacological agents for stimulating the collateral blood supply at appropriate time points. However, collateral recruitment appears to be a rapid, beneficial, endogenous mechanism that can be stimulated shortly after artery occlusion. It should be considered a treatment target for use in addition to recanalization strategies.
Highlights
The enhancement of collateral blood supply during the acute phase of cerebral ischemia could limit the extension of the core infarct by rescuing the penumbra area, and the degree of disability
middle cerebral artery (MCA) occlusion and transient common carotid artery (CCA) occlusion in two different mouse strains showed that native leptomeningeal collateralization accounted for rapid (30 min) retrograde flow recruitment, which continued to improve over 7 days in C57BL/6 mice, but not in Balb/C mice [14]
In the case of pre-Willis carotid artery occlusion, rerouting into the Willis circle is established side-to-side, via the azygos artery and both the posterior communicating artery (PcomA) in rodents, allowing reperfusion of the anterior cerebral artery (ACA) and posterior cerebral artery (PCA) territories, the vascular bed of the MCA being perfused via its borders by the leptomeningeal collaterals extending from the ACA and/or PCA
Summary
The enhancement of collateral blood supply during the acute phase of cerebral ischemia could limit the extension of the core infarct by rescuing the penumbra area, and the degree of disability. More invasive techniques have been used, but these require scalp incision, and, in adult rodents, a reduction of skull thickness (singlepoint laser Doppler flowmetry (LDF); laser speckle contrast imaging (LSCI) [10, 11]) or the creation of a cranial window (Sidestream Dark Field (SDF) [12]; two-photon imaging [13]; and optical coherence tomography (OCT) [14]). These invasive techniques can be used to visualize and quantify collateral recruitment at the surface of the brain, but with a depth of exploration limited to several microns. We will consider the pharmacological agents for stimulating collateral recruitment identified to date, before suggesting possible avenues of preclinical research to provide a comprehensive understanding of brain collateral recruitment
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