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Neuroprotection of sevoflurane against ischemia/reperfusion-induced brain injury through inhibiting GluN2A/GluN2B-PSD-95-MLK3 module

Abstract

To investigate the role of GluN2A and GluN2B in neuroprotective effect of sevoflurane preconditioning against cerebral ischemia–reperfusion injury (CIRI). Rats were randomly divided into five groups as follows: control, ischemia–reperfusion (I/R) 6 h, sevoflurane preconditioning (SP), SP + amantadine, SP + NMDA. Immunoblot and immunoprecipitation were used to detect the tyrosine phosphorylation of GluN2A/GluN2B, the interaction of GluN2A/GluN2B-PSD-95-MLK3 and the expression of phosphorylation of MLK3, MKK7 and JNK3. Cresyl violet staining was employed to analyse neuronal injury in rat hippocampal CA1 subfields. Sevoflurane preconditioning inhibits the tyrosine phosphorylation of GluN2A/GluN2B, the interaction of GluN2A/GluN2B-PSD-95-MLK3 and the phosphorylation of MLK3, MKK7 and JNK3 in rat hippocampus. An N-methyl-d-aspartate receptor (NMDAR) antagonist amantadine reversed the MLK3-MKK7- JNK3 signal events. Such reversion was also realized by NMDA (60 and 80 nmol) and low doses of NMDA (0–40 nmol) could not change the inhibitory effect of sevoflurane preconditioning on MLK3-MKK7-JNK3 signal events. Finally, Cresyl violet staining also confirmed that low dose of NMDA reduced neuronal loss in rat hippocampal CA1 subfields. Sevoflurane preconditioning provides neuroprotection against CIRI by inhibiting NMDAR over-activation.

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Correspondence to Lei Jin.

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Communicated by Sreedharan Sajikumar.

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Jin, L., Bo, X.M. Neuroprotection of sevoflurane against ischemia/reperfusion-induced brain injury through inhibiting GluN2A/GluN2B-PSD-95-MLK3 module. Exp Brain Res 239, 2701–2709 (2021). https://doi.org/10.1007/s00221-021-06157-x

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Keywords

  • Sevoflurane
  • GluN2A
  • GluN2B
  • MLK3
  • PSD-95
  • CIRI