Abstract T P409: Experimental Chronic Cerebral Hypoperfusion Results in Decreased Pericyte Coverage and Increased Blood Brain Barrier Permeability in the Corpus Callosum
Murine chronic cerebral hypoperfusion (CCH) results in white matter (WM) injury and behavioral deficits. Underlying mechanisms remain unclear. Pericytes influence blood-brain barrier (BBB) integrity and cerebral blood flow. Under hypoxic conditions, perictyes detach from perivascular locations increasing blood vessel permeability and secondary neuronal injury.
This study aims to characterize the time course of BBB dysfunction and pericyte coverage following murine experimental CCH. White matter injury and behavioral deficits have been reported consistently on post-operative day 30 in this model.
C57BL/6J mice underwent either CCH (n=12) or sham operation (n=9). BBB permeability in the corpus callosum (CC) was characterized on post-procedure days 1, 3, 7, and 30 using Evans blue (EB) extravasation and IgG staining. Pericyte coverage (CD 13/CD31 ratio) in the paramedian region of the corpus callosum was calculated on post-procedure days 1, 3, 7, and 30.
The CCH cohort demonstrated increased EB extravasation (integrate density) on postoperative days 1,3,7 and 30 when compared to the sham cohort (CCH: 583.58 ±98.28, 1529.32 ±448.87, 366.02 ±34.51, 5.85 ±1.80; SHAM: 44.51, 230.22, 24.03, 2.55 on postoperative days 1, 3, 7, and 30 respectively.) Further EB extravasation was significantly greater (p<0.05 ) at day 3 (peak level) than at days 7 and 30 in CCH mice. Positive IgG staining was seen at post-procedure days 3, 7, and 30 in the CCH group, but not in the sham operated mice. The CCH mice demonstrated a nadir in pericyte coverage on post-operative day 3 (30.88 ±10.27%). These values were significantly lower (p<0.05) than those on postoperative days 7 (89.36 ±5.11%), and 30 (74.97 ±2.39%). The post-operative day 3 pericyte coverage ratios were also significantly decreased compared to those in the sham mice (72.09 ±3.89%; p<0.01).
Decreased pericyte coverage and increased BBB permeability are most pronounced on postoperative day 3 following murine experimental CCH. This precedes any notable WM injury or behavioral deficits (post-op. day 30). Morphologic pericyte changes are concordant with BBB breakdown. Neurotoxic macromolecule extravasation may contribute to the pathogenesis of WM lesions and resultant behavioral deficits in this model system.
Author Disclosures: Q. Liu: None. R. Radwanski: None. R. Babadjouni: None. P. Baumbacher: None. J. Russin: None. Z. Zhao: None. W. Mack: Consultant/Advisory Board; Modest; Penumbra Inc- Member of DSMB for Thaerapy stroke and Liberty stent (aneurysm) trials.
- © 2015 by American Heart Association, Inc.