Abstract
Intraluminal occlusion of the middle cerebral artery (MCAo) in rodents is perhaps the most widely used model of stroke, however variability of infarct volume and the ramifications of this on sample sizes remains a problem, particularly for preclinical testing of potential therapeutics. Our data and that of others, has shown a dichotomous distribution of infarct volumes for which there had previously been no clear explanation. When studying perfusion computed tomography cerebral blood volume (CBV) maps obtained during intraluminal MCAo in rats, we observed inadvertent occlusion of the anterior choroidal artery (AChAo) in a subset of animals. We hypothesized that the combined occlusion of the MCA and AChA may be a predictor of larger infarct volume following stroke. Thus, we aimed to determine the correlation between AChAo and final infarct volume in rats with either temporary or permanent MCA occlusion (1 h, 2 h, or permanent MCAo). Outbred Wistar rats (n = 28) were imaged prior to and immediately following temporary or permanent middle cerebral artery occlusion. Presence of AChAo on CBV maps was shown to be a strong independent predictor of 24 h infarct volume (β = 0.732, p <0.001). This provides an explanation for the previously observed dichotomous distribution of infarct volumes. Interestingly, cortical infarct volumes were also larger in rats with AChAo, although the artery does not supply cortex. This suggests an important role for perfusion of the MCA territory beyond the proximal occlusion through AChA-MCA anastomotic collateral vessels in animals with a patent AChAo. Identification of combined MCAo and AChAo will allow other investigators to tailor their stroke model to reduce variability in infarct volumes, improve statistical power and reduce sample sizes in preclinical stroke research.
Highlights
Studies in both human and animals have reported large variability in the vascular anatomy of the brain
Of significance in the field of ischemic stroke research is the anatomy of the middle cerebral artery (MCA) and adjacent branches, in particular the anterior choroidal artery (AChA)
There were significant differences in infarct volume between animals with MCAo + AChAo compared to MCAo alone in the pMCAo group (42.7627.62 mm3 vs. 144.5611.72 mm3, p,0.0001, Figure 3A)
Summary
Studies in both human and animals have reported large variability in the vascular anatomy of the brain. Intraluminal thread occlusion of the MCA in the rat is the most common experimental model of stroke. This technique is performed by inserting an occluding monofilament suture via the ICA to occlude the origin of the MCA [4]. Advantages of this technique include lack of craniotomy and control over occlusion and reperfusion. One disadvantage of this model is the large variability in infarct volume. Factors thought to influence infarct volume variability include genetics [5], blood pressure [6], collateral blood flow [7], duration of vessel occlusion, and type of intraluminal thread used [8]
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