Inadvertent occlusion of the anterior choroidal artery explains infarct variability in the middle cerebral artery thread occlusion stroke model

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...

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Published inPloS one Vol. 8; no. 9; p. e75779
Main Authors McLeod, Damian D, Beard, Daniel J, Parsons, Mark W, Levi, Christopher R, Calford, Mike B, Spratt, Neil J
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 17.09.2013
Public Library of Science (PLoS)
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Summary: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.
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Competing Interests: The authors have declared that no competing interest exist.
Conceived and designed the experiments: DDM MWP CRL MBC NJS. Performed the experiments: DDM DJB MWP CRL NJS. Analyzed the data: DDM DJB NJS. Contributed reagents/materials/analysis tools: DDM DJB MWP CRL MBC NJS. Wrote the paper: DDM DJB MWP CRL MBC NJS.
Current address: Illawarra Health and Medical Research Institute and University of Wollongong, New South Wales, Australia
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0075779