A Semiquantitative Non-invasive Measurement of PcomA Patency in C57BL/6 Mice Explains Variance in Ischemic Brain Damage in Filament MCAo

Abstract

Numerous studies on experimental ischemic stroke use the filament middle cerebral artery occlusion (fMCAo) model in C57BL/6 mice, but lesion sizes in this strain are highly variable. A known contributor is variation in the posterior communicating artery (PcomA) patency. We therefore aimed to provide a semiquantitative non-invasive in vivo method to routinely assess PcomA patency. We included 43 male C57BL/6 mice from four independent studies using a transient 45 min fMCAo model. Edema-corrected lesion sizes were measured by magnetic resonance (MR) imaging 24 h after reperfusion. Timeof-flight MR angiography was performed 7 days before and 24 h after fMCAo. Scores of PcomA size measured 24 h after, but not scores measured 7 days before fMCAo were negatively correlated with lesion size. Variability in PcomA patency explained 30% of the variance in our cohort (p < 0.0001, coefficient of determination r 2 = 0.3). In a simulation using parameters typical for experimental stroke research, the power to detect a true effect of d = 1 between two groups increased by 15% when an according covariate was included in the statistical model. We have demonstrated that in vivo measurement of PcomA size is feasible and can lead to increased accuracy in assessing the effect of treatments.

Redefining the Koizumi model of mouse cerebral ischemia: A comparative longitudinal study of cerebral and retinal ischemia in the Koizumi and Longa middle cerebral artery occlusion models

“…This was further supported by our analysis of the recruitment of IL PcomA as an arterial collateral, which is a compensatory phenomenon occurring secondary to hypoperfusion. 28 , 29 Our analysis clearly demonstrated this phenomenon in the Koizumi group, but not in the Longa group. The most likely reason for the documented differences in reperfusion between the models is the permanent ligation of IL CCA in Koizumi vs transient ligation with full post-MCAO reperfusion of the IL CCA in Longa model, as previously suggested by others 31 , 32 and confirmed in our angiograms.…”

“…A manual quantitative assessment of the posterior communicating artery (PcomA) recruitment was performed based on previously described methods. 28 , 29 …”

Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex

“…Although the natural dynamics of cerebral collateral outgrowth and remodeling cannot be completely replaced by ex vivo modeling, we believe that reliable establishment of non-invasive, high-resolution CE-MRI has meaningful potential for reduction and refinement because CE-MRI facilitates an improved, longitudinal study design and intra-individual analysis with higher statistical power at the benefit of using a non-invasive technology (Nesselroade and Ram, 2004). For assessment of large caliber vessels, this hypothesis is supported by recent findings showing standardized and reliable time-of-flight (TOF) MR angiography for quantitative, longitudinal characterization of collateralization at the level of the Circle of Willis in mice (Foddis et al, 2020;Knauss et al, 2020). For assessment of collateral remodeling at the level of penetrating arterioles, however, the resolution of TOF MR angiography is too low and CE-MRA using a blood pooling agent could be better suited (Klohs et al, 2012).…”

Preserving mitochondrial function by inhibiting GRP75 ameliorates neuron injury under ischemic stroke

“…Mitochondrial fragmentation and dysfunction induced by ischemia in vivo. First, male c57Bl/6 mice were subjected to Mcao as a classical in vivo model of ischemic stroke (18). TTc staining indicated obvious infraction in the brain of Mcao model mice (Fig.…”

“…First, male C57BL/6 mice were subjected to MCAO as a classical in vivo model of ischemic stroke ( 18 ). TTC staining indicated obvious infraction in the brain of MCAO model mice ( Fig.…”