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Using a MPTP neurotoxin model of PD we tested the hypothesis that the protective actions of caffeine were because of, at least in part, preventing MPTP\u2010induced BBB dysfunction. FVB mice were pre\u2010treated with caffeine (10\u2003mg\/kg, i.p.) or saline for 7\u2003days prior to initiation of neurotoxin treatments; during the 7\u2003days of neurotoxin treatment, caffeine or saline continued to be administered 10\u2003min before each dose of MPTP (20\u2003mg\/kg, i.p.). Striatum (and for some studies hippocampus and cerebral cortex as well) were evaluated for BBB leakage, tight junction protein expression levels, integrity of dopaminergic neurons, and activation of astrocytes and microglia using immunostaining, immunoblotting and real\u2010time PCR techniques. We found that caffeine blocked MPTP\u2010induced decreases in numbers of tyrosine hydroxylase\u2010positive dopaminergic neurons, increases in leakage of Evan\u2019s blue dye and FITC\u2010albumin in striatum but not in cerebral cortex or hippocampus, decreases in levels of the tight junction proteins occludin and ZO\u20101, and increases in reactive gliosis. Our results suggest that caffeine might protect against PD and PD\u2010like features in animal models, in part, by stabilizing the BBB.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2008.05697.x","type":"journal-article","created":{"date-parts":[[2008,9,20]],"date-time":"2008-09-20T03:09:20Z","timestamp":1221880160000},"page":"1147-1157","source":"Crossref","is-referenced-by-count":166,"title":["Caffeine protects against MPTP\u2010induced blood\u2010brain barrier dysfunction in mouse striatum"],"prefix":"10.1111","volume":"107","author":[{"given":"Xuesong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Roche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rugao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Geiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,10,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007074420772"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1824"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.33.23463"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.07.021"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-19-07724.2001"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1052"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-004-0256-2"},{"key":"e_1_2_7_9_1","first-page":"39","article-title":"Structural and functional aspects of the blood\u2010brain barrier","volume":"61","author":"Begley D. 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