Pial Collateral Research Articles

Abstract 5108: Variation in Pial Collaterals in 15 Mouse Strains is a Major Determinant of Infarct Volume After Middle Cerebral Artery Occlusion (MCAO)

The importance of vascular, non-vascular and genetic factors in the wide variability in severity of infarct volume (IV) is unclear. We have reported previously that density and diameter of native collaterals in tissues vary widely with genetic background. The purpose of this study was to determine the contribution of genetic variation in collaterals to variation in IV in a cohort of genetic reference strains. IV was determined 1 day after MCAO. In a second set of mice, the vasculature was dilated, fixed and cast 6 days after MCAO. The number and diameter of pial collaterals were determined for the unligated left and ligated right hemispheres, as were territories of the MCA, ACA and PCA trees. Variations among strains in IV, native collateral number and diameter, and MCA, ACA and PCA territories were, respectively: 30-fold, 56-fold, and 3-fold, and 42%, 56% and 61%. IV and collateral dimensions did not correlate with brain size or PCA territory, but IV correlated highly with collateral number and diameter ((p<0.0001), and less so with MCA (p<0.05) and ACA territory (p<0.01). Arrangement of these parameters (excepting IV) into an expression of collateral conductance strongly predicted IV (p<0.0001). Prediction was improved by factoring in collateral length and hematocrit. There was no correlation between MCA territory and collateral number or diameter, suggesting genetic determinants of tree territory do not specify collateral dimensions. However, collateral dimensions were highly inter-correlated, suggesting they could arise from common genetic variants. Increase in collateral diameter on the ligated side (remodeling) varied by more than 2-fold and correlated with collateral diameter (p<0.0001) and number (p<0.01). Genome-wide haplotype and C57BL/6 × BALB/cBy F2 mapping are underway to identify potential loci harboring variants important in collateral formation. These data suggest that conductance of the pial collateral circulation is the primary determinant of stroke severity, and that polymorphisms in genes specifying formation of the native collateral circulation and its remodeling in ischemia are important determinants of stroke risk and stroke variance. These findings may generalize to heart, limb and other tissues.

Predictors of Hemorrhage Following Intra-Arterial Thrombolysis for Acute Ischemic Stroke: The Role of Pial Collateral Formation

The extent of pial collateral formation during acute ischemic stroke has been shown to influence outcomes. This study examines whether angiographic assessment of pial collateral formation is predictive of hemorrhagic transformation following intra-arterial thrombolysis (IAT) for acute ischemic stroke. Rates of any hemorrhage and significant hemorrhage (>25 mL) were reviewed in 104 consecutive patients who underwent IAT following acute ischemic stroke. The influence of the anatomic extent of pial collateral formation on the rates of hemorrhage and significant hemorrhage relative to known predictors for hemorrhagic transformation (presenting systolic blood pressure, blood glucose level, platelet level, and National Institutes of Health Stroke Scale [NIHSS] score, history of diabetes, time to treatment, age, sex, occlusion site, and extent of reperfusion) was analyzed by using logistic regression models. Rates of any hemorrhage and significant hemorrhage were 25.2% (26/104) and 9.7% (10/104), respectively. The rate of significant hemorrhage was 25.0% (8/32) in patients with poor pial collaterals and 2.78% (2/72) in those with good pial collaterals (P = .0004, Pearson correlation). The rate of any hemorrhage was also significantly higher in patients with poor pial collaterals (40.6% versus 18.1%; P = .0142, Pearson correlation). Logistic regression analyses revealed that pial collateral formation (odds ratio [OR] = 3.04), history of diabetes (OR = 4.83), platelets <200,000/microL (OR = 2.95), and time to treatment <3 hours (OR = 12.0) were statistically significant predictors of hemorrhage, whereas pial collateral formation (OR = 13.1) and platelets <200,000/microL (OR = 8.1) were statistically significant predictors of significant hemorrhage. Poor pial collateral formation is associated with higher incidence and larger size of hemorrhage following IAT.