Abstract WMP116: Age-related Dysfunction In Leptomeningeal Collateral Remodeling After Ischemic Stroke

Abstract

Introduction: The leptomeningeal collaterals (LMCs) are specialized brain surface arterioles that interconnect the major cerebral artery territories. Good outcome following ischemic stroke is highly correlated with high collateral number and function. Unfortunately, with aging and disease, the LMCs demonstrate impaired dilatory capacity, reduced vessel diameter, and even complete vessel loss (rarefaction). The present study examined the chronic remodeling capacity of LMCs following permanent stroke in young and aged mice. Methods: Young and aged C57BL6 mice (5 and 20 months) were subjected to permanent distal middle cerebral artery occlusion (pdMCAO). At 2 weeks or 3 months, LMCs were evaluated for inner diameter and VWF expression (% LMC coverage). We compared the LMCs feeding the occluded MCA territory (LMC ipsi) to the contralateral equivalent vessels (LMC contra). Diameter change is reported as fold change relative to the distal-most arteriole (DMA) associated with each LMC. Results: Young male mice demonstrated increased diameter of LMC ipsi relative to DMA at both 2 weeks (1.36 ± 0.075; n=24 vessels/4 mice, P<0.01) and 3 months after stroke (1.27 ± 0.073, n=19 vessels/2 mice, P<0.01). LMC contra were 0.901 ± 0.064 and 1.01 ± 0.053 for the same time points (n=19 and 10 vessels, P=NS). VWF expression was significantly increased in LMC ipsi at 2 weeks (ipsi 10.9 ± 2.87 vs. contra 2.91 ± 0.82, P<0.05) and neared significance at 3 months (ipsi 6.45 ± 1.54 vs. contra 2.06 ± 0.264, P=0.051). Aged mice demonstrated increased diameter of LMC ipsi relative to DMA at 2 weeks (1.24 ± 0.052, n=25 vessels from 3 mice, P<0.01), but not at 3 months (1.08 ± 0.044, n=14 from 2 mice, P=NS). Notably, the 3 month LMC ipsi vessels demonstrated irregular diameter and characteristics of rarefaction. LMC contra were 0.897 ± 0.032 and 0.967 ± 0.092 for the same time points (n=17 and 8 vessels, P=NS). VWF expression was significantly elevated in LMC ipsi vs. LMC contra at 2 weeks (6.74 ± 1.33 vs. 1.87 ± 0.361, P<0.01), but not at 3 months (2.27 ± 0.387 vs. 1.81 ± 0.398, P=NS). Conclusions: Our data show lasting LMC remodeling in young stroke brain, consisting of increased LMC diameter and expression of VWF. With aging, LMC remodeling is transient and evidence of LMC rarefaction is apparent by 3 months.