Genetic Knockout of TRPM2 Increases Neuronal Excitability of Hippocampal Neurons by Inhibiting Kv7 Channel in Epilepsy.

Epilepsy is a chronic brain disease that makes serious cognitive and motor retardation. Ion channels affect the occurrence of epilepsy in various ways, but the mechanisms have not yet been fully elucidated. Transient receptor potential melastain2 (TRPM2) ion channel is a non-selective cationic channel that can permeate Ca2+ and critical for epilepsy. Here, TRPM2 gene knockout mice were used to generate a chronic kindling epilepsy model by PTZ administration in mice. We found that TRPM2 knockout mice were more susceptible to epilepsy than WT mice. Furthermore, the neuronal excitability in the hippocampal CA1 region of TRPM2 knockout mice was significantly increased. Compared with WT group, there were no significant differences in the input resistance and after hyperpolarization of CA1 neurons in TRPM2 knockout mice. Firing adaptation rate of hippocampal CA1 pyramidal neurons of TRPM2 knockout mice was lower than that of WT mice. We also found that activation of Kv7 channel by retigabine reduced the firing frequency of action potential in the hippocampal pyramidal neurons of TRPM2 knockout mice. However, inhibiting Kv7 channel increased the firing frequency of action potential in hippocampal pyramidal neurons of WT mice. The data suggest that activation of Kv7 channel can effectively reduce epileptic seizures in TRPM2 knockout mice. We conclude that genetic knockout of TRPM2 in hippocampal CA1 pyramidal neurons may increase neuronal excitability by inhibiting Kv7 channel, affecting the susceptibility to epilepsy. These findings may provide a potential therapeutic target for epilepsy.

Miconazole exerts disease-modifying effects during epilepsy by suppressing neuroinflammation via NF-κB pathway and iNOS production.

Neuroinflammation contributes to the generation of epilepsy and has been proposed as an effective therapeutic target. Recent studies have uncovered the potential effects of the anti-fungal drug miconazole for treating various brain diseases by suppressing neuroinflammation but have not yet been studied in epilepsy. Here, we investigated the effects of different doses of miconazole (5, 20, 80 mg/kg) on seizure threshold, inflammatory cytokines release, and glial cells activation in the pilocarpine (PILO) pentylenetetrazole (PTZ), and intrahippocampal kainic acid (IHKA) models. We demonstrated that 5 and 20 mg/kg miconazole increased seizure threshold, but only 20 mg/kg miconazole reduced inflammatory cytokines release, glial cells activation, and morphological alteration during the early post-induction period (24 h, 3 days). We further investigated the effects of 20 mg/kg miconazole on epilepsy (4 weeks after KA injection). We found that miconazole significantly attenuated cytokines production, glial cells activation, microglial morphological changes, frequency and duration of recurrent hippocampal paroxysmal discharges (HPDs), and neuronal and synaptic damage in the hippocampus during epilepsy. In addition, miconazole suppressed the KA-induced activation of the NF-κB pathway and iNOS production. Our results indicated miconazole to be an effective drug for disease-modifying effects during epilepsy, which may act by attenuating neuroinflammation through the suppression of NF-κB activation and iNOS production. At appropriate doses, miconazole may be a safe and effective approved drug that can easily be repositioned for clinical practice.

Acupuncture therapy strategy options in postoperative management after laparoscopic cholecystectomy: A protocol for systematic review and Bayesian meta-analysis.

BACKGROUND: Laparoscopic cholecystectomy (LC) is a common surgery accompanied by some unpleasant adverse effects. Clinical trials indicated that acupuncture therapy may help reduce complications in LC. However, no systematic reviews have been conducted on the topic. Therefore, we will evaluate the current evidence and provide a rank for the efficacy of acupuncture therapy in LC by performing Bayesian network meta-analysis. METHODS: A total of 9 databases will be searched from inception to 10 December 2020. Randomized control trails met the criterion will be included. Quality evaluation of included studies will be performed using Cochrane risk-of-bias tool. STATA 14.0, Addis 1.16.8, R 3.6.3, and OpenBUGS 3.2.3 will be used to conduct pairwise meta-analysis and network meta-analysis. The evidence will be assessed by the Grades of Recommendations Assessment Development and Evaluation. RESULTS: This review will be based on clinical evidence to choose the best choice of acupuncture treatment for LC. And the results will be submitted to a peer-reviewed journal for publication. CONCLUSION: Through this systematic review, we will summarize the best available evidence of acupuncture therapy in LC and help to improve the clinical decision-making ability in LC domain. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered on INPLASY2020120056.

Performance analysis of compressive ghost imaging based on different signal reconstruction techniques.

We present different signal reconstruction techniques for implementation of compressive ghost imaging (CGI). The different techniques are validated on the data collected from ghost imaging with the pseudothermal light experimental system. Experiment results show that the technique based on total variance minimization gives high-quality reconstruction of the imaging object with less time consumption. The different performances among these reconstruction techniques and their parameter settings are also analyzed. The conclusion thus offers valuable information to promote the implementation of CGI in real applications.