Regional Variations in the Transport of Interleukin-1α across the Blood-Brain Barrier in ICR and Aging SAMP8 Mice

Abstract

Objectives: The blood-brain barrier (BBB) transports blood-borne interleukin-1α (IL-1) into the brain by a saturable process. Here, we determined whether all regions of the brain could transport IL-1 and whether transport differed between ICR and SAMP8 mice, a strain which overexpresses amyloid beta protein (Aβ) with aging. Methods: We used multiple-time regression analysis to measure the unidirectional influx rate (transport rate) of radioactively labeled IL-1 for 10 brain regions in young (2 months old) ICR mice and in young and aged (17 months old) SAMP8 mice. We also used radioactively labeled sucrose and albumin to determine whether the BBB was disrupted in aged SAMP8 mice. Results: In young ICR mice, eight of the 10 brain regions transported IL-1, with the pons-medulla having the fastest transport rate (0.584 ± 0.163 µl/g·min), but no statistically significant differences occurred among regions. In SAMP8 mice, only four regions transported IL-1. In young SAMP8 mice, the pons-medulla transported IL-1 faster than any other region (0.642 ± 0.197 µl/g·min), a rate that was significantly different (p < 0.01) from each of the other regions. Aged SAMP8 mice had a similar regional transport pattern to young SAMP8 mice, but there were no statistically significant differences among the four transporting regions. Sucrose and albumin spaces were not increased in aged SAMP8 mice, demonstrating an intact BBB. Conclusions: The smaller number of regions transporting IL-1 in SAMP8 mice as compared to ICR mice demonstrates a genetic influence on transport which could alter the ability of blood-borne IL-1 to directly affect brain functions. No evidence of BBB disruption was found in the aged SAMP8 mice from this colony.