Increasing Permeability of Blood Brain Barrier with Senescence from Leukocytes
Hafezi-Moghadam A.1,3, Thomas K. L.1, Wagner D. D.1,2
1The Center for Blood Research, Boston/USA; 2Department of Pathology; 3Department of Pediatrics, Childrens Hospital, Harvard Medical School, Boston/USA
Purpose: Brain vessels provide a unique barrier function (blood brain barrier) that protects the central nervous system from harmful blood born molecules. Various age-related neuro-degenerative diseases, such as Alzheimers disease or Age-Related Macula Degeneration, have a vascular component. However, little is known about senescence of the blood brain or blood retina barrier. Therefore, we hypothesized that the integrity of the blood brain barrier (BBB) may be subject to changes with age.
Method: Using Evans Blue dye we quantified permeation of plasma proteins into the cortex of wild type mice and mice deficient for apo-liopoprotein E, CD18, ICAM-1, and P-selectin.
Results: In wild type mice we found a significant increase in the permeability of BBB with age (r2=0.27, P<0.01). To investigate the underlying mechanisms, we examined mice deficient for adhesion molecules involved in inflammatory leukocyte recruitment (ICAM-1-/-, CD18-/-, P-selectin-/-) and apoE deficient mice, which are prone to inflammatory conditions. In ICAM-1-/-, CD18-/-, and P-selectin-/- mice we found a reduced age-related compromise in BBB-function. ApoE-/- mice, however, show an exacerbated age-related increase in their BBB-p
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