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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Article info
Publication history
Published online: November 15, 2022
Accepted:
November 10,
2022
Received in revised form:
October 27,
2022
Received:
July 27,
2022
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106896
Copyright
© 2022 Elsevier Inc. All rights reserved.
