Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse striatum.

Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse striatum.
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DOI:
10.1111/j.1471-4159.2008.05697.x
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发表时间:
2008-11
影响因子:
4.7
通讯作者:
Geiger JD
Geiger JD
中科院分区:
医学2区
文献类型:
--
作者:
Chen X;Lan X;Roche I;Liu R;Geiger JD

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The blood-brain barrier (BBB) is important physiologically. Pathologically, BBB disruption has been implicated in a wide spectrum of neurological disorders including Parkinson's disease (PD). Recent studies indicate that caffeine is protective against PD, but by poorly understood mechanisms. Using a MPTP neurotoxin model of PD we tested the hypothesis that the protective actions of caffeine were due to, at least in part, preventing MPTP-induced BBB dysfunction. FVB mice were pretreated with caffeine (10 mg/kg, i.p.) or saline for 7 days prior to initiation of neurotoxin treatments; during the 7 days of neurotoxin treatment, caffeine or saline continued to be administered 10 min before each dose of MPTP (20 mg/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-time PCR techniques. We found that caffeine blocked MPTP-induced decreases in numbers of TH-positive dopaminergic neurons, increases in leakage of Evan's blue dye and FITC-albumin in striatum but not in cerebral cortex or hippocampus, decreases in levels of the tight junction proteins occludin and ZO-1, and increases in reactive gliosis. Our results suggest that caffeine might protect against PD and PD-like features in animal models, in part, by stabilizing the BBB.
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