Time-course of blood-brain barrier disruption in senescence-accelerated mouse prone 8 (SAMP8) mice

Senescence of the cerebrovascular system and an abnormal function of the blood-brain barrier have been related with Alzheimer's disease. We studied here the time-course of blood-brain barrier disruption in senescence-accelerated mouse prone 8 (SAMP8) mice, which is a murine model of senescence and is also considered a model of Alzheimer's disease. We used a previously described method that allows evaluating blood-brain barrier integrity by observing Evans blue extravasation from brain blood vessels. Three brain regions (cortex, hippocampus and hippocampal fissure) of SAMP8 brains were analyzed at 3, 6, 9, 12 and 15 months of age, Moreover, genetically related senescence-accelerated mouse resistant 1 (SAMR1) and ICR-CD1 mice were studied. Results indicate that Evans blue permeability in SAMP8 and SAMR1 increases from 6 to 15 months in the three studied regions. At 15 months of age, SAMP8 and SAMR1 mice showed higher Evans blue extravasation in CA1 and Fissure than ICR-CD1 mice. Further studies are required to understand the senescence process in SAMR1 mice, as blood-brain barrier alterations in old age have unexpectedly been observed. on the other hand, as blood-brain barrier permeability in SAMP8 mice increases with age, blood-brain barrier alterations may contribute to the cerebral pathology observed in this strain. (C) 2008 ISDN. Published by Elsevier Ltd. All rights reserved.