Effects Of Colistin On Blood-brain Barrier,Amino Acid Neurotransmitters And PC12 Cell Membrane

Neurotoxicity is one of the major potential side effects of colistin therapy. However, the mechanistic aspects of colistin-induced neurotoxicity remain largely unknown. The objective of this study was to examine the effects of colistin on the blood-brain barrier(BBB) and amino acid neurotransmitters in the cerebral cortex of mouse. Mice were divided into four groups(n=5) and were administrated intravenously with 15 mg/kg/day of colistin sulfate for 1, 3 and 7 days successively while the control group was administrated intravenously with saline solution. The permeability and ultrastructure of the BBB were detected using the Evans blue(EB) dye and transmission electron microscopy(TEM), and the expression of Claudin-5 were determined by real-time PCR examination and western blotting. The brain uptake of colistin was measured by high-performance liquid chromatography(HPLC). The effects of colistin on amino acid neurotransmitters and their receptors were also examined by HPLC and real-time PCR. In order to determine the effect of colisin sulfate on PC12 cells membrane, the PC12 cells were passage cultured and treated with 62.5 and 125 μg·m L-1colistin sulfate for 24 h, respectively.(1)The results of EB extravasation, TEM and expression of Claudin-5 showed that colistin treatment did not affect the BBB integrity.(2)In addition, multiple doses of colistin could induce accumulation of this compound in the brain parenchyma although there was poor brain uptake of colistin.(3)Moreover, colistin exposure significantly increased the contents of Glu and GABA, and enhanced the m RNA expression levels of their receptors.(4)The results showed that the cells stimulated with 125 μg·m L-1 colistin could damaged cell membrane. In a word, our findings may be associated with colistin-induced neurotoxicity.