Transient versus Permanent MCA Occlusion in Mice Genetically Modified to Have Good versus Poor Collaterals

Med One. 2019:4:e190024. doi: 10.20900/mo.20190024. Epub 2019 Nov 27.


Collateral-dependent blood flow is capable of significantly lessening the severity of stroke. Unfortunately, collateral flow varies widely in patients for reasons that remain unclear. Studies in mice have shown that the number and diameter of cerebral collaterals vary widely due primarily to polymorphisms in genes, e.g., Rabep2, involved in their formation during development. However, understanding how variation in collateral abundance affects stroke progression has been hampered by lack of a method to reversibly ligate the distal middle cerebral artery (MCAO) in mice. Here we present a method and examine infarct volume 24 h after transient (tMCAO, 90 min) versus permanent occlusion (pMCAO) in mice with good versus poor collaterals. Wildtype C57BL/6 mice (have abundant collaterals) sustained small infarctions following tMCAO that increased 2.1-fold after pMCAO, reflecting significant penumbra present at 90 min. Mutant C57BL/6 mice lacking Rabep2 (have reduced collaterals) sustained a 4-fold increase in infarct volume over WT following tMCAO and a smaller additional increase (0.4-fold) after pMCAO, reflecting reduced penumbra. Wildtype BALB/cBy (have a deficient Rabep2 variant and poor collaterals) had large infarctions following tMCAO that increased less (0.6-fold) than the above wildtype C57BL/6 mice following pMCAO. Mutant BALB/cBy mice (have deficient Rabep2 replaced with the C57BL/6 variant thus increased collaterals) sustained smaller infarctions after tMCAO. However, unlike C57BL/6 versus Rabep2 mice, penumbra was not increased since infarct volume increased only 0.3-fold following pMCAO. These findings present a murine model of tMCAO and demonstrate that neuroprotective mechanisms, in addition to collaterals, also vary with genetic background and affect the evolution of stroke.

Keywords: MCA ligation; collaterals; ischemic stroke; permanent; transient.