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

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          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.

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          Most cited references 5

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          Correlation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline

           Jan Näslund (2000)
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            Blood-borne interleukin-1 receptor antagonist crosses the blood-brain barrier.

            Recent work has shown that interleukin-1 alpha (IL-1 alpha) and IL-1 beta are transported from blood to brain across the blood-brain barrier by a saturable system. Here, we show that the endogenous IL-1 receptor antagonist (IL-1ra) radioactively labeled with either 125I or 35S is also transported across the blood-brain barrier by a saturable transport system. Between 0.33 and 0.65% of an intravenous dose of labeled IL-1ra entered each gram of brain. The three cytokines inhibited each other's transport in a way suggesting that their elevated blood levels would tend to favor the entry of IL-1 beta at the expense of IL-1 alpha. High performance liquid chromatography confirmed that radioactivity entering the brain represented intact cytokine. Recovery of radioactivity from cerebrospinal fluid, an area without blood vessels, and from the parenchymal fraction of the cortex, and area without circumventricular organs, after capillary depletion confirmed that blood-borne IL-1ra gained entry into the brain. The transport system for IL-1ra appeared to be linked to that for IL-1 alpha and IL-1 beta, but was not affected by IL-2, IL-6, TNF alpha, or MIP-1 alpha. The results show that IL-1ra circulating in the blood can cross the blood-brain barrier to enter the central nervous system.
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              Age-related changes in footshock avoidance acquisition and retention in senescence accelerated mouse (SAM)


                Author and article information

                S. Karger AG
                March 2001
                09 March 2001
                : 8
                : 4
                : 165-170
                GRECC, Veterans Affairs Medical Center-St. Louis and Department of Internal Medicine, Division of Geriatrics, Saint Louis University School of Medicine, St. Louis, Mo., USA
                54814 Neuroimmunomodulation 2000;8:165–170
                © 2001 S. Karger AG, Basel

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                Figures: 2, Tables: 1, References: 39, Pages: 6
                Original Paper


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