舒血宁注射液联合阿托伐他汀治疗老年慢性硬膜下血肿的临床研究

目的探讨舒血宁注射液联合阿托伐他汀治疗慢性硬膜下血肿的临床疗效。方法选取2016年1月—2017年1月在天津医科大学总医院滨海医院治疗的慢性硬膜下血肿患者76例,依据治疗方案的差别分为对照组(38例)和治疗组(38例)。对照组口服阿托伐他汀钙片,20 mg/次,1次/d。治疗组在对照组的基础上静脉滴注舒血宁注射液,20 mL加入5%葡萄糖溶液250 mL,1次/d。两组患者均治疗30 d。评价两组患者临床疗效,同时比较治疗前后两组患者CSS和ADL评分以及血肿量和血清学指标。结果治疗后,对照组和治疗组的总有效率分别为81.58%、97.37%,两组比较差异具有统计学意义(P0.05)。治疗后,两组CSS评分与血肿量均显著降低,ADL评分升高,同组比较差异具有统计学意义(P0.05);且治疗组CSS和ADL评分及血肿量均显著优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清神经元特异性烯醇化酶(NSE)、基质金属蛋白酶-9(MMP-9)、脑源性神经营养因子(BDNF)水平显著降低,同组比较差异具有统计学意义(P0.05);且治疗组上述血清学指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论舒血宁注射液联合阿托伐他汀治疗慢性硬膜下血肿临床疗效显著,可有效改善神经功能和促进血肿吸收,具有一定的临床推广应用价值。     

棕榈酸帕利哌酮长效针剂联合认知行为干预治疗首发精神分裂症疗效观察

目的比较棕榈酸帕利哌酮长效针剂联合认知行为干预对首发精神分裂症患者的疗效和预后的影响,及治疗后外周血脑源性神经营养因子（BDNF）水平的变化。方法将120例首发精神分裂症患者按随机数字表法分为棕榈酸帕利哌酮长效针剂联合认知行为干预组（联合治疗组）和单用棕榈酸帕利哌酮长效针剂组（单用药组）,每组各60例,进行为期12个月的治疗。评定两组患者治疗前（基线）及治疗后3、6、9、12个月的阳性和阴性症状量表（PANSS）、不良反应量表（TESS）、个人和社会功能评分（PSP）量表、用药满意度问卷（MSQ）,以评估疗效、安全性、社会功能和用药满意度,同时比较两组患者临床缓解率和复发率。采用酶联免疫法检测治疗前后外周血BDNF水平。结果联合治疗组临床缓解率为89.4%,高于单用药组的69.6%（P＜0.05）;复发率为1.8%,低于单用药组的7.1%（P＜0.05）;联合治疗组治疗后不同时点PANSS和PSP评分改善均优于单用药组（均P＜0.05）;两组患者治疗后BDNF水平均显著升高,但是联合组用药BDNF水平升高更多。两组患者TESS评分比较差异无统计学意义（P＞0.05）,联合治疗组不同时点MSQ评分均优于单用药组（均P＜0.05）。结论棕榈酸帕利哌酮长效针剂联合认知行为干预能明显提高精神分裂症患者的临床缓解率,降低复发率,能安全有效地用于精神分裂症的维持治疗,并且显著提高患者外周血BDNF水平。     

Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10

The heptapeptide Semax, an analogue of the N-terminal adrenocorticotropic hormone fragment (4-10) (ACTH(4-10)), has been shown to exert a number of neuroprotective effects. There are some investigations that connected these effects with the increase of neurotrophin gene expression under the peptide drug application in neuron cell cultures [M.I. Shadrina, O.V. Dolotov, I.A. Grivennikov, P.A. Slominsky, L.A. Andreeva, L.S. Inozemtseva, S.A. Limborska, N.F. Myasoedov, Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analogue, Neurosci. Lett. 308 (2001) (2) 115-118]. In this work, we examined the action of Semax on rapid changes of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in vivo. Male Wistar rats were treated for 1h with Semax (50 microg/kg, single intranasal application) and neurotrophin gene expression in rat brain was analyzed by real-time polymerase chain reaction (PCR). It was revealed that an intranasal application of Semax increased the expression of both neurotrophin genes in rat hippocampus. Bdnf gene expression also increased in the brainstem and cerebellum. Ngf gene expression decreased in rat frontal cortex. Thus, Semax induces rapid, gene- and region-specific changes in neurotrophin gene expression in normal rat brain.     

RNA interference-mediated inhibition of brain-derived neurotrophic factor expression increases cocaine's cytotoxicity in cultured cells

Previous studies showed that cocaine exposure decreased brain-derived neurotrophic factor (BDNF) function and resulted in neuronal cell death. To investigate a role of BDNF in cocaine's cytotoxicity, an RNA interference (RNAi) approach was used. Transfection of neuroblastoma SK-N-AS cells or primary rat hippocampal neurons with the small double-stranded interfering RNA (siRNA) targeting BDNF mRNA, but not the scrambled siRNA, resulted in reductions in levels of BDNF mRNA and proteins by more than 70% in the transfected cells as compared with the control group, suggesting an RNAi-mediated, sequence-specific gene silencing. The results also showed that cocaine-induced cytotoxicity, assessed by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazodium bromide) assay, was more pronounced in the cells transfected with the siRNA than in the cells transfected with the scrambled siRNA or in the cells treated with Lipofectamine 2000 alone (the control group), suggesting that inhibition of BDNF expression enhances cocaine's cytotoxicity. Together with previous studies showing that cocaine suppresses BDNF expression, the present data suggest that the drug-induced reduction of BDNF productions may make neurons more vulnerable to cocaine's toxic effects and precipitate cocaine-induced central nervous system damages.     

BDNF tagging polymorphisms and haplotype analysis in sporadic Parkinson's disease in diverse ethnic groups

Experimental and clinical data suggest that genetic variations in brain-derived neurotrophic factor (BDNF) gene may affect risk for Parkinson's disease (PD). We performed a case-control association analysis of BDNF in three independent Caucasian cohorts (Greek, North American, and Finnish) of PD using eight tagging SNPs and five constructed haplotypes. No statistically significant differences in genotype and allele frequencies were found between cases and controls in all series. A relatively rare BDNF haplotype showed a trend towards association in the Greek (p=0.02) and the Finnish (p=0.03) series (this haplotype was not detected in the North American series). However, given the large number of comparisons these associations are considered non-significant. In conclusion, our results do not provide statistically significant evidence that common genetic variability in BDNF would associate with the risk for PD in the Caucasian populations studied here.     

Tinnitus behavior and hearing function correlate with the reciprocal expression patterns of BDNF and Arg3.1/arc in auditory neurons following acoustic trauma

The molecular changes following sensory trauma and the subsequent response of the CNS are poorly understood. We focused on finding a molecular tool for monitoring the features of excitability which occur following acoustic trauma to the auditory system. Of particular interest are genes that alter their expression pattern during activity-induced changes in synaptic efficacy and plasticity. The expression of brain-derived neurotrophic factor (BDNF), the activity-dependent cytoskeletal protein (Arg3.1/arc), and the immediate early gene c-Fos were monitored in the peripheral and central auditory system hours and days following a traumatic acoustic stimulus that induced not only hearing loss but also phantom auditory perception (tinnitus), as shown in rodent animal behavior models. A reciprocal responsiveness of activity-dependent genes became evident between the periphery and the primary auditory cortex (AI): as c-Fos and BDNF exon IV expression was increased in spiral ganglion neurons, Arg3.1/arc and (later on) BDNF exon IV expression was reduced in AI. In line with studies indicating increased spontaneous spike activity at the level of the inferior colliculus (IC), an increase in BDNF and GABA-positive neurons was seen in the IC. The data clearly indicate the usefulness of Arg3.1/arc and BDNF for monitoring trauma-induced activity changes and the associated putative plasticity responses in the auditory system.     

Can we increase the speed and efficacy of antidepressant treatments? Part II. Glutamatergic and RNA interference strategies

In the second part we focus on two treatment strategies that may overcome the main limitations of current antidepressant drugs. First, we review the experimental and clinical evidence supporting the use of glutamatergic drugs as fast-acting antidepressants. Secondly, we review the involvement of microRNAs (miRNAs) in the pathophysiology of major depressive disorder (MDD) and the use of small RNAs (e.g.., small interfering RNAs or siRNAs) to knockdown genes in monoaminergic and non-monoaminergic neurons and induce antidepressant-like responses in experimental animals.The development of glutamatergic agents is a promising venue for antidepressant drug development, given the antidepressant properties of the non-competitive NMDA receptor antagonist ketamine. Its unique properties appear to result from the activation of AMPA receptors by a metabolite [(2 S,6 S;2 R,6 R)-hydroxynorketamine (HNK)] and mTOR signaling. These effects increase synaptogenesis in prefrontal cortical pyramidal neurons and enhance serotonergic neurotransmission via descending inputs to the raphe nuclei. This view is supported by the cancellation of ketamine's antidepressant-like effects by inhibition of serotonin synthesis.We also review existing evidence supporting the involvement of miRNAs in MDD and the preclinical use of RNA interference (RNAi) strategies to target genes involved in antidepressant response. Many miRNAs have been associated to MDD, some of which e.g., miR-135 targets genes involved in antidepressant actions. Likewise, SSRI-conjugated siRNA evokes faster and/or more effective antidepressant-like responses. Intranasal application of sertraline-conjugated siRNAs directed to 5-HT_1A receptors and SERT evoked much faster changes of pre- and postsynaptic antidepressant markers than those produced by fluoxetine.     

重复经颅磁刺激联合盐酸帕罗西汀对卒中后抑郁症患者治疗效果观察

目的 探讨重复经颅磁刺激(rTMS)联合盐酸帕罗西汀对卒中后抑郁症(PSD)患者HAMD评分及血清神经肽Y(NPY)、促肾上腺皮质激素释放因子(CRF)、脑源性神经营养因子(BDNF)水平变化的影响。 方法 选取郑州大学第二附属医院2014年11月至2017年2月PSD患者68例,随机数字表法分组,各34例。对照组采用盐酸帕罗西汀,观察组采用盐酸帕罗西汀+rTMS,两组均持续治疗2个月。入院时及治疗结束后统计对比两组抑郁评分(HAMD、MARDS、SDS)、血清NPY、BDNF、CRF水平、临床疗效及不良反应发生率。 结果 ①两组治疗后MARDS、HAMD及SDS分值低于治疗前,且观察组较对照组低(P＜0.05);②两组治疗有效率比较,观察组94.12%(32/34)较对照组64.71%(22/34)高(P＜0.05);③两组治疗后血清CRF水平低于治疗前,BDNF及NPY水平高于治疗前,且观察组各指标优于对照组(P＜0.05);④两组不良反应发生率比较,观察组14.71%(5/34)与对照组8.82%(3/34)间差异无统计学意义(P＞0.05)。 结论 联合采用盐酸帕罗西汀及rTMS治疗卒中后抑郁症效果显著,可有效改善血清NPY、BDNF、CRF水平,降低HAMD评分,减轻患者抑郁程度,提高治疗效果,且不会增加不良反应发生风险,具有安全性。     

Protective effect of ginsenoside Rh2 on scopolamine‐induced memory deficits through regulation of cholinergic transmission,oxidative stress and the ERK‐CREB‐BDNF signaling pathway

Rh2 is a rare ginsenoside and there are few reports of its effect on cognition compared with other similar molecules. This study aimed to establish the impact of Rh2 treatment on improving scopolamine (Scop)‐induced memory deficits in mice and illuminate the underlying mechanisms. First, memory‐related behavior was evaluated using two approaches: object location recognition (OLR), based on spontaneous activity, and a Morris water maze (MWM) task, based on an aversive stimulus. Our results suggested that Rh2 treatment effectively increased the discrimination index of the mice in the OLR test. In addition, Rh2 elevated the crossing numbers and decreased the escape latency during the MWM task. Moreover, Rh2 markedly upregulated the phosphorylation of the extracellular signal‐regulated kinase (ERK)‐cAMP response element binding (CREB)‐brain derived neurotrophic factor (BDNF) pathway in the hippocampus. Meanwhile, the administration of Rh2 significantly promoted the cholinergic system and dramatically suppressed oxidative stress in the hippocampus. Taken together, Rh2 exhibited neuroprotective effects against Scop‐induced memory dysfunction in mice. Rh2 activity might be ascribed to several underlying mechanisms, including its effects on modulating the cholinergic transmission, inhibiting oxidative stress and activating the ERK‐CREB‐BDNF signaling pathway. Consequently, the ginsenoside Rh2 might serve as a promising candidate compound for Alzheimer's disease.