关键词： Cerebral ischemia   WNT   beta-catenin   TWS119   Microglial polarization   Neuroinflammation   Neurological recovery  

摘要： Background Ischemic stroke is a leading cause of disability worldwide and characteristically accompanied by downregulation of the Wnt/beta-catenin signaling. Activation of Wnt/beta-catenin signaling emerges to attenuate neuroinflammation after ischemic stroke;however, its effect on modulating microglial polarization is largely unknown. Here, we explored whether Wnt/beta-catenin pathway activator TWS119 facilitated long-term neurological recovery via modulating microglia polarization after experimental stroke. Methods Ischemic stroke mice model was induced by permanent distal middle cerebral artery occlusion plus 1 h hypoxia. TWS119 was administrated from day 1 to 14 after stroke. Neurological deficits were monitored up to 21 days after stroke. Angiogenesis, neural plasticity, microglial polarization, and microglia-associated inflammatory cytokines were detected in the peri-infarct cortex at days 14 and 21 after stroke. Primary microglia and mouse brain microvascular endothelial cell lines were employed to explore the underlying mechanism in vitro. Results TWS119 mitigated neurological deficits at days 14 and 21 after experimental stroke, paralleled by acceleration on angiogenesis and neural plasticity in the peri-infarct cortex. Mechanistically, cerebral ischemia induced production of microglia-associated proinflammatory cytokines and priming of activated microglia toward pro-inflammatory polarization, whereas TWS119 ameliorated microglia-mediated neuroinflammatory status following ischemic stroke and promoted angiogenesis by modulating microglia to anti-inflammatory phenotype. The beneficial efficacy of TWS119 in microglial polarization was largely reversed by selective Wnt/beta-catenin pathway blockade in vitro, suggesting that TWS119-enabled pro-inflammatory to anti-inflammatory phenotype switch of microglia was possibly mediated by Wnt/beta-catenin signaling. Conclusions Wnt/beta-catenin pathway activator TWS119 ameliorated neuroinflammatory microenvironment fol

关键词： speech delay   seizures   Drosophila   mustard   T2A-GAL4   MiMIC   oxidative stress   TLDc   NCOA7   V-ATPase  

摘要： We report an early-onset autosomal-recessive neurological disease with cerebellar atrophy and lysosomal dysfunction. We identified biallelic loss-of-function (LoF) variants in Oxidative Resistance 1 (OXR1) in five individuals from three families;these individuals presented with a history of severe global developmental delay, current intellectual disability, language delay, cerebellar atrophy, and seizures. While OXR1 is known to play a role in oxidative stress resistance, its molecular functions are not well established. OXR1 contains three conserved domains: LysM, GRAM, and TLDc. The gene encodes at least six transcripts, including some that only consist of the C-terminal TLDc domain. We utilized Drosophila to assess the phenotypes associated with loss of mustard (mtd), the fly homolog of OXR1. Strong LoF mutants exhibit late pupal lethality or pupal eclosion defects. Interestingly, although mtd encodes 26 transcripts, severe LoF and null mutations can be rescued by a single short human OXR1 cDNA that only contains the TLDc domain. Similar rescue is observed with the TLDc domain of NCOA7, another human homolog of mtd. Loss of mtd in neurons leads to massive cell loss, early death, and an accumulation of aberrant lysosomal structures, similar to what we observe in fibroblasts of affected individuals. Our data indicate that mtd and OXR1 are required for proper lysosomal function;this is consistent with observations that NCOA7 is required for lysosomal acidification.

关键词： Cervical spinal cord injury without fracture and dislocation   CSCIWFD   SCI   Early surgery   Timing of surgery   Fused segments  

摘要： Objective: The purpose of this study was to investigate the effects of the number of fused segments, the timing of surgery and their interaction on the prognosis of patients with cervical spinal cord injury without fracture and dislocation (CSCIWFD), and to determine the appropriate time restrictions for early surgery in CSCIWFD patients based on the current diagnosis and treatment system in southern China. Methods: CSCIWFD patients who underwent anterior cervical decompression and internal fusion (ACDF) from January 2012 to June 2017 were selected. The patients were grouped according to the timing of surgery and the number of fused segments and evaluated based on their American Spinal Injury Association (ASIA) score, ASIA impairment scale, and Japanese Orthopaedic Association (JOA) score before and after surgery. SPSS22.0 software was used for the statistical analysis. Results: The ASIA score, JOA score, and ASIA impairment scale in all follow-ups were significantly higher than before surgery (p < 0.05). The ASIA and JOA scores at 6, 12, and 24 months after surgery of the patients who underwent ACDF within 72 h were significantly better than those of the patients who underwent ACDF after 72 h (p < 0.05). There were significant differences in postoperative ASIA and JOA scores at 12 and 24 months between the short-segment and three-segment fusion groups (p < 0.05). The results of the interaction between the surgical timing and the number of the fused segments showed that the postoperative ASIA and JOA scores at 6, 12, and 24 months were significantly higher in the patients who underwent early short-segment fusion than in those who underwent delayed shortsegment fusion (p < 0.05). However, no statistically significant difference was found between early and delayed surgery in the patients who underwent three-segment fusion (p > 0.05). Conclusion: ACDF is safe and effective for the treatment of CSCIWFD. For patients with single- or double-segment injury, early (within 7

关键词： Porphyria   neurology   psychiatry   neurovisceral porphyria  

摘要： Porphyrias are inherited disorders of the heme biosynthetic pathway, usually characterized by dermatological changes due to the accumulation of byproducts in the pathway. Select porphyrias also affect the nervous system, namely hereditary coproporphyria, acute intermittent porphyria and variegate porphyria. Complications include paralysis, hyponatremia which can risk central pontine myelinolysis, seizures and coma. Neurological complications usually result from severe episodes of acute attacks. Acute attacks may also elicit neuropsychiatric symptoms such as confusion, hallucinations, anxiety and psychosis. However, these manifestations are generally self-limiting. Due to the generally low incidence of porphyria and full knowledge the associated neurological and psychiatric manifestations, we review the relevant porphyrias along with their clinical manifestations, evaluation, and management to raise its awareness in the clinical picture and to prevent misdiagnosis. Porphyria should be considered within the differential diagnosis for unexplained neurological symptoms.

关键词： 心脏病学   急诊医学   急诊科   管理指南   晕厥   老年医学   临床专业知识   神经病学  

摘要： 晕厥是由于多种原因引起的一过性脑灌注不足导致短暂性意识丧失,一般为突然发作,迅速完全恢复。2018年欧洲心脏病学会(ESC)颁布了新的晕厥诊断和管理指南,对比前一版(2009年版)的指南具有如下特点:①多学科的专家委员会组成,涵盖了心脏病学、内科学、老年医学、急诊医学、神经病学等多个学科,由各个学科共同制定晕厥的诊断和临床处理策略;②该指南强调以患者为导向,核心目标是减少晕厥再发和危及生命的后果,重点是如何管理和治疗,基于此目标,即使在缺乏充分实验数据的情况下,专家组根据临床专业知识,尽可能给出治疗和决策方案;③新指南提出晕厥患者从急诊科开始的处理路径,指导临床建立晕厥门诊,以达到减少住院,减少漏诊和误诊,高度关注路径和机构问题,优化晕厥诊断流程等目的。本文将就上述问题进行阐述。

关键词： 南京鼓楼医院   江苏省医学会   中华医学会   神经系统疾病   神经病学   神经变性疾病   脑血管病   内科主任医师  

摘要： 【受访专家】赵辉南京鼓楼医院神经内科主任医师,南京大学、南京医科大学副教授,医学博士,硕士研究生导师。中华医学会神经病学分会痴呆与认知障碍学组委员,江苏省医学会神经病学分会认知障碍学组副组长,江苏省卒中分会认知精神障碍专委会副主任委员。获华夏医学科技奖及江苏医学科技奖,发表SCI文章20余篇。擅长神经变性疾病、脑血管病等神经系统疾病的诊治,尤其是痴呆的诊断及治疗。

关键词： 轻度认知障碍   声音刺激   轻度认知功能障碍   深度睡眠   阿尔茨海默病   改善记忆   慢波睡眠   神经病学  

摘要： 2019-06-28发表在《临床与转化神经病学年鉴》上的报告发现,深度睡眠中的声音刺激改善了轻度认知障碍患者的记忆。在深度睡眠的特定时期进行的温和声音刺激可以增强患有轻度认知功能障碍的人的深度或慢波睡眠,这些患者有阿尔茨海默病的风险。大脑对声音刺激作出最强烈反应的个体在第2天表现出改善记忆的反应。

关键词： 《神经病学与神经康复学杂志》   神经康复学   神经病学   缩略词   原创研究  

摘要： 《神经病学与神经康复学杂志》(CN:31-1927/R;ISSN:1672-7061)由上海市卫生和计划生育委员会主管,上海中西医结合学会、上海交通大学医学院附属仁济医院主办,是国内外公开发行的神经病学与神经康复学领域的专业学术期刊.

关键词： CEREBRAL small vessel diseases   OPTIC nerve injuries   RETINAL imaging   NEUROLOGICAL disorders