| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
Statins have a neuroprotective effect in neurological diseases, a pleiotropic effect possibly related to blood-brain barrier (BBB) function. In this study, we investigated the effects of statin on lipopolysaccharide (LPS)-induced BBB dysfunction in in vitro BBB model comprising co-culture of primary mouse brain endothelial cells, pericytes, and astrocytes. LPS (1 ng/ml, 24 hr) induced the impairment of permeability and transendothelial electrical resistance (TEER). Co-administration of statin alleviated the deleterious effects of LPS on BBB permeability and TEER. LPS increased IL-6, G-CSF, KC, MCP-1, RANTES release from our BBB model. Statin inhibited all these LPS-induced cytokine production. These data suggest that pitavastatin could ameliorate LPS-induced BBB dysfunction, which might be mediated by inhibiting LPS-induced cytokine production. Our present finding sheds light on the pharmacological significance of statins in various kinds of CNS diseases.
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