Inhibition of protein tyrosine phosphatase 1B protects against sevoflurane-induced neurotoxicity mediated by ER stress in developing brain

ER stress is involved in sevoflurane-induced neurotoxicity. Protein tyrosine phosphatase 1B (PTP1B) resided in the ER membrane is known to regulate ER stress. However, the role of PTP1B in sevoflurane-induced neurotoxicity is unknown. Method: Seven-day-old mice treated with 2.3% sevoflurane for 6 h as animal model. The hippocampal tissues were harvested following sevoflurane exposure for evaluation of ER stress markers with Western blot, ER morphology with transmission electron microscopy and density of dendrite spine with Golgi staining. In another subset of mice, neurocognitive function was assessed 4 weeks after anesthesia using Morris water maze test. We also examined the effects of PTP1B or PERK inhibitor on sevoflurane-induced neurodegeneration in the hippocampus. Result: The

Our study shows PTP1B inhibition mitigates sevoflurane-induced neurodegeneration maybe mediated by ER stress in developing brain, and eventually improves cognitive function. This suggests PTP1B inhibition could represent a promising strategy to prevent sevoflurane-induced neurotoxicity.