An Endovascular Canine Middle Cerebral Artery Occlusion Model for the Study of Leptomeningeal Collateral Recruitment

Abstract

Objectives This work aimed to refine a large animal in minimally invasive reversible middle cerebral artery (MCA) occlusion (MCAO) model to account for leptomeningeal collateral formation. Materials and Methods An angiographically based methodology allowed for transient MCA and carotid terminus occlusion in 12 mongrel dogs and assessment of pial collateral recruitment. Outcome measures included 1- and 24-hour magnetic resonance imaging-based infarct volume calculation, a behavioral scale and histopathologic sections. Results MCAO succeeded in 8 of 12 dogs (67% efficiency). One-hour postreperfusion infarct volume predicted 24-hour postreperfusion infarct volume (r2 = 0.997, P < 0.0001). Pial collateral recruitment varied with time and reproducibly assessed predicted infarct volume on 1-hour postre-perfusion mean diffusivity maps (P < 0.0001; r2 = 0.946) and 24-hour fluid-attenuated inversion recovery FLAIR magnetic resonance imaging (P < 0.0033; r2 = 0.961). The canine stroke scale score correlated with infarct volumes and pial collateral score. Conclusion This canine MCAO model produces defined cerebral infarct lesions whose volumes correlate with leptomeningeal collateral formation and canine behavior.

Tocotrienol Vitamin E Protects against Preclinical Canine Ischemic Stroke by Inducing Arteriogenesis

“…Furthermore, the current experimental model benefits from C-arm fluoroscopy visualization of MCAO. As opposed to the widely used rodent intraluminal thread model of MCAO, this method permits repeated real-time documentation of the stroke event, improving the overall reproducibility of the procedure and enabling objective assessment of collateral circulation during cerebral ischemia (Christoforidis et al, 2011). In this work, the latter proved to be pivotal in identifying the effects of TE on perfusion of the stroke-affected brain tissue.…”

“…Digital subtraction angiogram acquisitions obtained just before reperfusion were reviewed to assess cerebrovascular collateral recruitment using an 11-point scale, as previously described (Christoforidis et al, 2011). This scale takes into account the anatomic extent and transit time of leptomeningeal collaterals from the posterior and anterior cerebral artery circulations to the affected MCA territory.…”

An endovascular canine stroke model: middle cerebral artery occlusion with autologous clots followed by ipsilateral internal carotid artery blockade

“…10 Notably, the thread-like clots were cut into about 1.4 and 1.7 mm in diameter and 5 mm in length, and then were placed in a sterilized Petri dish containing normal saline. The animal was initially administered a bolus of 2500 U of heparin 18 and left femoral vein access was maintained with a saline drip (2 ml/min).…”

“…An 11-point scale was implemented in this study, which took into account the anatomic extent and transit time of leptomeningeal collateral circulations from the posterior and anterior cerebral arteries to the affected MCA territory 18 .…”

“…However, segmental occlusion of one single vessel (eg, middle cerebral artery (MCA)) in dogs often cannot produce significant defects 10,14,15 because of compensation due to their leptomeningeal collateral circulation. Abundant collateral blood flow could develop from the distal area to the occluded locus before an irreversible ischemic lesion could happen, 2,10,[16][17][18] which results in a major mismatch between the size of infarct area and the territory of the vessel occlusion. Lipsanen and Jolkkone 19 reported that consecutive lesions could be produced by MCA occlusion (MCAO) followed by ipsilateral intracranial blood supply artery blockade in rat stroke models.…”