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Dexmedetomidine (Dex) exerts protective effects on rat neuronal cells injured by cerebral ischemia/reperfusion via regulating the Sphk1/S1P signaling pathway

      Abstract

      Aim

      To investigate the influence of dexmedetomidine (Dex) on cerebral ischemia/reperfusion (I/R)-injured rat neuronal cells by regulating the Sphk1/S1P pathway.

      Methods

      The rats were divided into the following groups, with 18 rats in each group categorized on the basis of random number tables: sham (Sham), I/R (I/R), Dex, Sphk1 inhibitor (PF-543), and Dex together with the Sphk1 agonist phorbol-12-myristate-13-acetate (Dex+PMA). The neurological functions of the rats were assessed by the Longa scoring system at 24 h post reperfusion. The area of brain infarction was inspected using 2,3,5-triphenyltetrazolium chloride staining, and the water content of brain tissue was determined by the dry-wet weight method. The morphology of neurons in the CA1 region of the rat hippocampus was inspected using Nissl staining, while the apoptosis of neurons in this region was detected by terminal-deoxynucleotidyl transferase mediated nick end labeling staining. The Sphk1 and S1P protein levels were determined by immunofluorescence and western blotting, respectively.

      Results

      Compared to the I/R group, rats in the Dex, PF-543, and Dex+PMA groups had a significantly lower neurological function score, as well as lower brain water content and a decreased infarction area. Moreover, the apoptotic index of the neurons and the Sphk1 and S1P levels in the hippocampal CA1 region were significantly lower in these groups (p<0.05). PMA, an agonist of Sphk1, was able to reverse the protective effects of Dex on I/R-induced neuronal cell injury.

      Conclusion

      Dex could protect cerebral I/R-induced neuronal cell injury by suppressing the Sphk1/S1P signaling pathway.

      Keywords

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