Temporal remodeling of pial collaterals and functional deficits in a murine model of ischemic stroke

小鼠缺血性中风模型中软脑膜侧支的时间重塑和功能缺陷

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作者:Benjamin Okyere, Miranda Creasey, Yeonwoo Lebovitz, Michelle H Theus

Background

Leptomeningeal anastomoses play a critical role in regulating reperfusion following cerebrovascular obstruction; however,

Conclusions

This simple and reproducible combination of techniques is the first to dissect the temporospatial remodeling of pial collateral arterioles. The method will advance investigations into the underlying mechanisms governing the intricate processes of arteriogenesis.

Methods

Compared to polyurethane and latex methods for collateral labeling, this new method provides detailed cell-type specific analysis within the collateral niche at the microscopic level, which has previously been unavailable. Conclusions: This simple and reproducible combination of techniques is the first to dissect the temporospatial remodeling of pial collateral arterioles. The method will advance investigations into the underlying mechanisms governing the intricate processes of arteriogenesis.

Results

While the overall density was not influenced by pMCAO, the size of MCA-ACA and MCA-PCA vessels had significantly increased 2days post-pMCAO and peaked by 4days compared to the un-injured hemisphere. Using a combination of vessel painting and immunofluorescence, we uniquely observed an induction of cellular division and a remodeling of the smooth muscle cells within the collateral niche following post-pMCAO on whole mount tissue sections. Vessel painting was also applied to pMCAO-injured Cx3cr1GFP mice, in order to identify the spatial relationship between Cx3cr1-positive peripheral-derived monocyte/macrophages and the vessel painted collaterals. Our histological findings were supplemented with analysis of cerebral blood flow using laser Doppler imaging and behavioral changes following pMCAO. Comparison with existing methods: Compared to polyurethane and latex methods for collateral labeling, this new method provides detailed cell-type specific analysis within the collateral niche at the microscopic level, which has previously been unavailable. Conclusions: This simple and reproducible combination of techniques is the first to dissect the temporospatial remodeling of pial collateral arterioles. The method will advance investigations into the underlying mechanisms governing the intricate processes of arteriogenesis.

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