Regional variations in the transport of interleukin-l alpha across the blood-brain barrier in ICR and aging SAMP8 mice

Objectives: The blood-brain barrier (BBB) transports blood-borne interleuki n-1 alpha (IL-1) into the brain by a saturable process. Here, we determined whether all regions of the brain could transport IL-1 and whether transpor t differed between ICR and SAMP8 mice, a strain which overexpresses amyloid beta protein (A beta) with aging. Methods: We used multiple-time regressio n analysis to measure the unidirectional influx rate (transport rate) of ra dioactively labeled IL-1 for 10 brain regions in young (2 months old) ICR m ice and in young and aged (17 months old) SAMP8 mice. We also used radioact ively labeled sucrose and albumin to determine whether the BBB was disrupte d in aged SAMP8 mice. Results: In young ICR mice, eight of the 10 brain reg ions transported IL-1, with the pons-medulla having the fastest transport r ate (0.584 +/- 0.163 mul/g.min), but no statistically significant differenc es 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 o ther region (0.642 +/- 0.197 mul/g.min), a rate that was significantly diff erent (p < 0.01) from each of the other regions. Aged SAMP8 mice had a simi lar regional transport pattern to young SAMP8 mice, but there were no stati stically significant differences among the four transporting regions. Sucro se 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 aff ect brain functions. No evidence of BBB disruption was found in the aged SA MP8 mice from this colony. Copyright (C) 2001 S. Karger AG, Basel.