Abstract
Statins have neuroprotective effects on neurological diseases, including a pleiotropic effect possibly related to blood–brain barrier (BBB) function. In this study, we investigated the effects of pitavastatin (PTV) on lipopolysaccharide (LPS)-induced BBB dysfunction in an in vitro BBB model comprising cocultured primary mouse brain endothelial cells, pericytes, and astrocytes. LPS (1 ng/mL, 24 h) increased the permeability and lowered the transendothelial electrical resistance of the BBB, and the co-administration of PTV prevented these effects. LPS increased the release of interleukin-6, granulocyte colony-stimulating factor, keratinocyte-derived chemokine, monocyte chemotactic protein-1, and regulated on activation, normal T-cell expressed and secreted from the BBB model. PTV inhibited the LPS-induced release of these cytokines. These results suggest that PTV can ameliorate LPS-induced BBB dysfunction, and these effects might be mediated through the inhibition of LPS-induced cytokine production. Clinically, therapeutic approaches using statins combined with novel strategies need to be designed. Our present finding sheds light on the pharmacological significance of statins in the treatment of central nervous system diseases.
Highlights
Statins reduce serum low-density lipoprotein (LDL) cholesterol levels by inhibiting3-hydroxyl-3-methyl coenzyme A (HMG-CoA) reductase
The anti-inflammatory effects of statins have been noted in previous studies, and we predicted that statins could counter the pro-inflammatory effects of LPS on the blood–brain barrier (BBB)
We investigated the influence of LPS on BBB function and the protective effects of PTV on LPS-induced BBB dysfunction
Summary
Statins reduce serum low-density lipoprotein (LDL) cholesterol levels by inhibiting. Statins have various unique pleiotropic effects in addition to cholesterol-lowering activity. Statins have been demonstrated to have beneficial effects against many central nervous system (CNS) diseases and conditions including stroke, Alzheimer’s disease, multiple sclerosis, brain trauma, and infection [1,2,3,4,5,6,7,8]. “new-generation” statins, which have a stronger cholesterollowering effect than conventional statins, have been developed. The new-generation statin pitavastatin (PTV) exerts potent hypolipidemic effects in both animal and human trials [9]. Reports of its pleiotropic effects on endothelial cells have been published [10,11].
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