GABAergic deficiency contributes the pathophysiology of schizophrenia. The present study investigates the therapeutic effectiveness of low-concentration sevoflurane, a volatile anesthetic with GABAergic modulating activity, in MK801-induced schizophrenia-like mice and schizophrenia patients. Three weeks after MK801 administration (0.5 mg/kg, twice/day, 5 days), mice were exposed to 1% sevoflurane 1hr/day for 5 days. Behavioral tests, immunohistochemical analysis, western blot assay and electrophysiology assessments were performed 1week post-exposure. Ten schizophrenia patients received 5hr sevoflurane (0.5%-1.2%) for 6 days, and were assessed with PANSS and the BPRS-18 at week 1 and week 2. MK801 induced social deficits, downregulated expression of NMDARs subunits and postsynaptic density protein 95 (PSD95), reduced parvalbumin- and GAD67-positive neurons, altered the amplitude and frequency of mEPSC (miniature excitatory postsynaptic current) and mIPSC (miniature inhibitory postsynaptic current), and increased the excitation/inhibition ratio; all of which were attenuated by sevoflurane. Sevoflurane also significantly ameliorated schizophrenia symptoms in patients at 1st and 2nd week post-inhalation. Our work demonstrated that low-concentration sevoflurane inhalation effectively reversed MK801-induced schizophrenia-like disease in mice and alleviated clinical symptoms of schizophrenia in patients, highlighting sevoflurane as a potential therapy for the management of schizophrenia.

Background and Purpose: Surgery remains the first-line treatment of ovarian cancer. However, perioperative risk factors including the choice of anaesthetics may influence its recurrence after surgery. In the current study, it was hypothesised that inhalational anaesthetic sevoflurane and intravenous anaesthetic propofol might affect cancer cellular metabolism and signalling, which might interfere the malignancy of ovarian cancer cells. Experimental Approach: Cultured ovarian cancer cells were exposed to 2.5% sevoflurane or administered with 4 μg/mL propofol for 2 hours followed by 24 hours recovery. Their cell viability, proliferation, migration and invasion were assessed using cell counting kit-8, Ki-67 staining, wound healing and Transwell assay. Cellular signalling biomarkers were measured using immunofluorescent staining and/or Western blot. Cultured media were collected for 1H-NMR spectroscopy-based metabolomics analysis. Key Results: The cell viability, proliferation, migration, and invasion of ovarian cancer cells were enhanced by sevoflurane but suppressed by propofol. Sevoflurane increased the GLUT1, MPC1, GLUD1, p-Erk1/2, and HIF-1α expressions but decreased the PEDF expression. In contrast to the sevoflurane treatment, the “mirror changes” of these cellular markers were observed with propofol. Sevoflurane increased levels of isopropanol but decreased glucose and glutamine levels in the media, but the opposite changes of those metabolites were found after propofol treatment. Conclusion and Implications: These data indicated that unlike propofol, sevoflurane enhanced ovarian cancer cell metabolism and activated PEDF/Erk/HIF-1α cellular signalling pathway, suggesting that sevoflurane might have pro-tumour property but propofol might afford an anti-tumour property. The translational value of this work warrants further study.