Minocycline Pretreatment Prevents Blood-Brain Barrier Disruption in Septic Rats.

Abstract

The aim of the study was to explore the mechanism by which minocycline protects the blood-brain barrier (BBB) in septic rats. A sepsis rat model was generated in healthy, male Sprague-Dawley rats by cecal ligation and puncture (CLP). The rats were randomly divided into four groups and treated as follows: sham-operated plus normal saline (Sham+S group), CLP plus normal saline (CLP+S group), CLP plus minocycline pretreatment (CLP+M1 group), and CLP plus minocycline treatment (CLP+M2 group). Rats in the CLP+M1 group received 45mg/kg minocycline by intraperitoneal injection every 12h for 72h. Rats in the Sham+S and CLP+S groups were injected with the same volume of normal saline every 12h for 72h. Rats in the CLP+M2 group were intraperitoneally injected with 45mg/kg minocycline immediately after CLP and once every 12h for 72h. All rats were sacrificed at 72h after operation. Tumor necrosis factor α and interleukin 6 levels, the expression of ionized calcium-binding adaptor molecule-1 (Iba-1), and the permeability of the BBB were measured. The expression of matrix metalloproteinases-9 (MMP-9) and the tight junction proteins zonula occludens-1 (ZO-1) and occludin was detected by Western blot. In addition, Evans blue (EB) staining, immunohistochemistry, and ELISA analysis were carried out. Minocycline pretreatment significantly inhibited microglial activation, decreased the sepsis-induced expression of MMP-9, increased the expression of ZO-1 and occludin, and improved the permeability of the BBB. Minocycline treatment failed to inhibit microglial activation, decrease the sepsis-induced expression of MMP-9, increase the expression of ZO-1 or occluding, or improve the permeability of the BBB. Minocycline pretreatment can effectively improve the altered permeability of the BBB caused by sepsis. The mechanism may be related to the inhibition of microglial activation and MMP-9 expression and increased expression of ZO-1 and occludin.