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.

Objective Programmed intermittent epidural bolus (PIEB) was reported to provide superior maintenance of labour analgesia with better pain relief, and less motor block than continuous epidural infusion (CEI). Whether this is also evident for uterine contraction pain relief after caesarean section remains unknown. Design Randomised, double blind, positive-control trial. Setting Guangzhou Women and Children’s Medical Center, China Population Parturients scheduled for elective caesarean section under combined spinal-epidural anaesthesia were enrolled. Methods At the end of the surgery, after a similar epidural loading dose given, patients received either PIEB (6 mL every hour) or CEI (6 mL/h) of 0.1% ropivacaine. Main outcome measures The primary outcome was the effectiveness of uterine contraction pain relief during breastfeeding assessed with visual analog scale score (VAS-UD) at the postoperative 36 h. Secondary main outcome was lower extremity motor block (defined as Bromage score > 0). Results One hundred and twenty parturients were studied (PIEB, 60; CEI, 60). The VAS-UD at the postoperative 36 h was significantly lower in the PIEB group than in the CEI group [median (IQR), 30 (20 to 40) mm] compared with the CEI group [40 (30 to 50) mm], with an estimated difference of -10 mm (95% CI -15 to -5 mm; P=0.001). Motor block was higher in the CEI group than in the PIEB group during the study period except 2 h (all P<0.05). Conclusions PIEB provides more effective uterine contraction pain relief and less motor block after caesarean section than CEI.