Abstract 16279: Traumatic Brain Injury-Induced Increased Pial Venular Permeability is Ameliorated With Endothelial Progenitor Cells and the Stromal Vascular Fraction Cells in Mice
Traumatic brain injury (TBI) is a devastating public health problem worldwide. It is accompanied with an increased cerebrovascular permeability to blood proteins. It is suggested that impairment in endothelial cell properties can be a main cause of enhanced vascular permeability, and thus vasculo-neuronal degeneration. We tested the hypothesis that TBI-induced an increase in cerebrovascular permeability can be ameliorated by repairing vascular endothelium via increasing number of endothelial progenitor cells (EPCs) or injecting the stromal vascular fraction cells (SVFCs) based on their capacity of self-regeneration. Permeability of pial venules in pericontusional area was studied in C57BL/6J mice brain after mild TBI. Mouse bone marrow-derived cells were grown on tissue culture plates to confluence and Flk-1+/Sca-1+ (markers of endothelial and stem cell phenotype, respectively) EPCs were isolated by flow cytometry sorting. SVFCs from mouse adipose tissue were collected via enzymatic tissue dissociation. After induction of mild TBI, mice were infused with EPCs or with SVFCs (~106 cells) suspended in 100 μl of phosphate buffered saline (PBS) or with PBS alone (control group) through the tail vein. After 10-14 days, pial venular permeability in these mice was assessed by measuring the extravascular accumulation of fluorescently-labeled bovine serum albumin (BSA) using an intravital fluorescence microscope. The protein leakage to interstitium was analyzed by changes in the ratio of fluorescence intensity in the interstitium to that inside the respective vascular segment. The measurements were done 1 hour after injection of BSA and were expressed as a percent of baseline (10 minutes after BSA injection). Cerebrovascular leakage was lesser in mice infused with EPCs (136 ± 4 % of baseline) and with SVFCs (131 ± 3 %) compared to that in mice infused with PBS alone (186 ± 6 %). These results suggest that TBI-induced increased cerebrovascular permeability can be reversed by enhancing the number of EPCs and with SVFCs, which can restore impaired property of vascular endothelium or cerebral microvascular network in pericontusional area. Our data indicate a novel functional role of EPCs and SVFCs in post-TBI treatment of cerebrovascular pathology.
Author Disclosures: N. Muradashvili: None. R. Tyagi: None. J. Dale: None. R.L. Benton: None. S.C. Tyagi: Research Grant; Modest; NIH HL-071010, NIH NS-051568. Research Grant; Significant; NIH NS-084823. T.E. O’Toole: Research Grant; Significant; NIH ES019217. J.B. Hoying: Research Grant; Significant; NIH EB007556. D. Lominadze: Research Grant; Modest; NIH P30 GM-103507. Research Grant; Significant; NIH NS-084823.
- © 2014 by American Heart Association, Inc.