Sevoflurane anesthesia represses neurogenesis of hippocampus neural stem cells via regulating microRNA-183-mediated NR4A2 in newborn rats.

Sevoflurane has been commonly utilized in nonobstetric surgeries in pregnant women, and its impacts on fetal brain are still not completely known. Ectopic NR4A2 expression has been reported to be related with familial Parkinson disease, and through dual luciferase we found that NR4A2 is a target gene of microRNA-183 (miR-183). We proposed a hypothesis that miR-183 may participate in the process by targeting NR4A2 in neurons after sevoflurane anesthesia. To verify the effect of sevoflurane on hippocampal neural stem cells (NSCs) proliferation and differentiation, we conducted EdU assay and immunofluorescence staining. Next, for better understanding of the impact of miR-183, we altered the miR-183 expression using mimic and inhibitor. Meanwhile, the targeting relationship between miR-183 and NR4A2 was validated by a bioinformatics website and dual-luciferase reporter gene assay. Finally, expressions of miR-184, NR4A2, SRY (sex-determining region Y)-box 2 (Sox2), and brain-derived neurotrophic factor (BDNF) were determined and evaluated by reverse transcription quantitative polymerase chain reaction and western blot analysis. First, sevoflurane was determined a crucial factor in biological behaviors of hippocampal NSCs. Moreover, upregulated miR-183 expression by mimic inhibited the proliferation and differentiation of NSCs. Sevoflurane negatively regulated NR4A2 and Sox2 expressions but positively regulated miR-183 and BDNF expressions. Our findings revealed the underlying novel mechanism by which sevoflurane inhibits hippocampal NSC proliferation and differentiation through interaction with miR-183 and NR4A2. The study provides reliable reference for safe application of sevoflurane anesthesia in neonates.

Protective effect of notoginsenoside R1 in a rat model of myocardial ischemia reperfusion injury by regulation of Vitamin D3 upregulated protein 1/NF-κB pathway.

The aim of this study was to investigate the protective effects of notoginsenoside R1 (R1) in the rat model of myocardial ischemia reperfusion injury and the possible mechanisms. Myocardial ischemia/reperfusion injury (MIRI) was induced by ischemia for 30 min and reperfusion for 60 min. Fifty male SD rats (250-300 g), were randomly divided into 5 groups: sham, model, R1 (20 mg/kg, 40 mg/kg, 60 mg/kg). The activities of serum lactate dehydrogenase (LDH), creatine kinase (CK), myeloperoxidase (MPO), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were determined after 60 min of reperfusion. Interleukin-1ß (IL-1ß), interleukin-8 (IL-8) and tumor necrosis factor (TNF)-α were evaluated by enzyme-linked immunosorbent assay (ELISA), Vitamin D3 Upregulated Protein 1 (VDUP1), IκB α, P-IκB α, NF-κBP65, pNF-κBP65 were measured by western blotting. Our study demonstrated that R1 can ameliorate the impaired mitochondrial morphology and oxidation system; IL-1 ß, IL-8 and TNF-α were recovered. Western blotting studies demonstrated that R1 substantially inhibited p-IκBα, NF-κBP65, p-NF-κBP65 protein levels and increased VDUP1 protein level. These findings suggest that R1 may effectively ameliorate the progression of 1/R injury and could be used as a therapy for patients with myocardial ischemia/reperfusion injury.

[Effect of electroacupuncture at governor vessel on learning-memory ability and serum level of APP, Aß1-42 in patients with Alzheimer's disease].

OBJECTIVE: To compare the therapeutic effect of electroacupuncture (EA) combined with donepezil hydrochloride and donepezil hydrochloride alone on improving learning-memory ability in patients with Alzheimer's disease (AD), and to explore its action mechanism. METHODS: Sixty patients of AD were randomly divided into an observation group and a control group, 30 cases in each group. The patients in the observation group were treated with EA at governor vessel (GV) combined with donepezil hydrochloride. EA was applied at Baihui (GV 20) and Fengfu (GV 16) with dilatational wave (10 Hz/50 Hz of frequency, 0.5 to 5.0 mA of intensity), and the needles were kept for 40 min, EA was given once a day; the donepezil hydrochloride tablet was taken orally, 5 mg, once a day, and after 4 weeks the dosage might be increased to 10 mg per day according to the specific situation. All the treatment was given for 8 weeks. The patients in the control group were only treated with donepezil hydrochloride with the identical procedure as the observation group. The Montreal cognitive assessment (MoCA) and Alzheimer's disease assessment scale cognitive part (ADAS-Cog) were evaluated before and after treatment; P300 (latency and amplitude of N2 and P3) was detected by EEG/ERP system brain event related potential instrument, and amyloid precursor protein (APP) and ß-amyloid protein 1-42 (Aß1-42) were detected by ELISA. RESULTS: Compared before treatment, the MoCA scores were increased after treatment in the two groups (P<0.05), and the MoCA score in the observation group was higher than that in the control group (P<0.05). Compared before treatment, the ADAS-Cog scores were decreased after treatment in the two groups (P<0.05), and the ADAS-Cog score in the observation group was lower than that in the control group (P<0.05). Compared before treatment, the latency of N2 and P3 was shortened and the amplitude was increased after treatment in the two groups (P<0.05); after treatment, the latency of N2 and P3 in the observation group was shorter than that in the control group and the amplitude was higher than that in the control group (P<0.05). Compared before treatment, the serum levels of APP and Aß1-42 were lower after treatment in the two groups (P<0.05), and the serum levels of APP and Aß1-42 in the observation group were lower than those in the control group (P<0.05). CONCLUSION: EA at Baihui (GV 20) and Fengfu (GV 6) combined with donepezil hydrochloride can effectively reduce the serum levels of APP and Aß1-42 and improve the scores of MoCA and ADAS-Cog and the levels of N2 and P3 of P300 in AD patients, which has superior effect to donepezil hydrochloride alone in improving the learning-memory of AD patients.

[Effects of cluster needling at the scalp points on the expression of ChAT and AchE of hippocampus in rats with Alzheimer's disease].

OBJECTIVE: To explore the effects of cluster needling at the scalp points on the expression of choline acetyl transferase (ChAT) and choline cholinesterase (AchE). METHODS: A total of 60 Wistar rats were randomized into a sham-operation group, a model group, a medication group and a cluster needling group, 15 rats in each one. In the model group, the medication group and the cluster needling group, the models of Alzheimer's disease (AD) were established by the orienteering injection with Aß1-42 in the bilateral hippocampal CA1 in the rats. In the sham-operation group, the distilled water was injected in bilateral hippocampus of rats. In the medication group, the lavage with aricept was adopted for the basic treatment, once a day, for 4 weeks consecutively. In the cluster needling group, on the base of the treatment as the medication group, the cluster needling at the scalp points was adopted, once a day, 6 times a week, for 4 weeks totally. In the sham-operation group and the model group, the normal feeding was provided. After intervention, the learning and memory ability was measured with Morris water maze in the rats of each group. The changes in the hippocampal gross structure were observed with HE staining. The changes in the positive expressions of hippocampal ChAT and AchE were determined with the immunohistochemical method. RESULTS: Compared with the sham-operation group, the escape latency was prolonged and the percentage of the second quadrant and the frequency of platform leaping were reduced in the rats of the model group (all P<0.01). Compared with the model group, the escape latency was shortened and the percentage of the second quadrant and the frequency of platform leaping were increased in the rats of the cluster needling group and the medication group (P<0.05, P<0.01). Compared with the medication group, the escape latency was shortened and the percentage of the second quadrant and the frequency of platform leaping were increased in the rats of the cluster needling group (all P<0.05). Compared with the sham-operation group, the expression of ChAT was decreased and that of AchE increased in the model group (both P<0.01). Compared with the model group, the difference was not significant in ChAT expression (P>0.05) and the expression of AchE was reduced (P<0.05) in the medication group; the expression of ChAT was increased (P<0.05) and that of AchE decreased (P<0.01) in the cluster needling group. Compared with the medication group, the expression of ChAT was increased and that of AchE decreased in the cluster needling group (both P<0.05). CONCLUSION: The effect mechanism of cluster needling at the scalp points on AD could be related to the up-regulation of ChAT expression and down-regulation of AchE expression in the hippocampus. The combined treatment with the cluster needling and aricept achieves the better therapeutic effect on AD.