Collateral Supply in Preclinical Cerebral Stroke Models

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.

Benefits of Endovascular Treatment in Late Window for Acute Ischemic Stroke Selected without CT Perfusion: A Real-World Study

“… 30 , 31 On the other hand, the status of collaterals is considered to be a critical determinant for distinguishing between “rapid progressing” and “slow progressing”, 32 and robust collaterals can effectively prevent the extension of the core infarct by rescuing the penumbra area. 33 Therefore, in the extended time window, patients with a small core, moderate to good collateral, are by definition “slow progressors” who can potentially benefit most from recanalization penumbra, 14 , 34 , 35 and these are also important factors for achieving good outcomes in our study.…”

Astrocyte-neuron lactate shuttle plays a pivotal role in sensory-based neuroprotection in a rat model of permanent middle cerebral artery occlusion

“…The superimposition of Paxinos and Watson's rat brain atlas according to the slices' landmarks show the resulting infarct following pMCAo in a case where the lactate transport is blocked over large cortical area (largest skull-dura-slits). The superimposition of TTC slices with the rat brain atlas shows infarct covering parts of primary motor cortex, primary somatosensory cortex, auditory cortex all the way up to parts of primary visual cortex, spanning almost the entire MCA territory 41 .…”

The Updated Role of Transcranial Ultrasound Neuromodulation in Ischemic Stroke: From Clinical and Basic Research

“…After ischemic stroke, the neurons in the stroke center rapidly undergo apoptosis and necrosis because of ischemia and hypoxia, whereas the surrounding cells still have transient survival ability because of the existence of collateral circulation, thus forming an ischemic penumbra. Within a certain period of time, cells in this area can either undergo apoptosis or return to the normal brain tissue (Bonnin et al, 2021;Davis and Donnan, 2021;Yang and Liu, 2021). If the ischemic penumbra is rescued in time, it can effectively prevent stroke progression; further, the successful rescue of ischemic penumbra is also conducive to the recovery of the nervous system and physical function in the future.…”