Limbic epilepsy is a common brain disorder associated with dysregulation of micronutrients, of which vitamin D plays an important role in neuronal survival, neurotransmitter homeostasis and synaptic transmission. However, the in vivo contribution of vitamin D to epileptogenesis remains unclear. In this study, we observed a significant increase in vitamin D receptor (VDR) mRNA level at 6-12 h after seizure onset in four distinct classic epilepsy models. Vitamin D receptor protein expression also increased following pilocarpine-induced seizures, particularly in the hippocampal granule cell layer. Subsequently, we found that aberrant vitamin D dietary levels could accelerate kindling development. To our surprise, excessive vitamin D intake reduced the frequency of spontaneous seizures in the pilocarpine model, whereas vitamin D deficiency decreased mossy fibre sprouting-a hallmark of epileptogenesis. These findings provide new insights into the mechanisms underlying limbic epileptogenesis.

Traumatic brain injury (TBI) is an important cause of disability and mortality, and identifying effective neuroprotective drugs and targets after TBI is an urgent public concern. Ferroptosis, an iron dependent, novel form of cell death associated with lipid peroxidation, has recently been shown to participate in secondary injury processes after TBI. Fisetin is a natural and relatively safe at general dosages flavonoid compound with neuroprotective properties. This study aimed to investigate the molecular mechanism of ferroptosis in TBI and the role of fisetin in neuroprotection by regulating ferroptosis and oxidative stress following TBI. Through in vivo experiments, a mouse model of repetitive mild closed head injury was established to determine that fisetin could reduce post-TBI injury and exert neuroprotective effects as determined by the Neurobehavioral Severity Scale score, brain water content, Nissl staining, hematoxylin-eosin staining, TUNEL staining and water maze experiment results. Fisetin was proven to be capable of inhibiting the changes in post-TBI ferroptosis proteins, activating the PI3K/AKT/NRF2 signaling pathway, and reducing oxidative stress, as confirmed by Western blotting. Via in vitro experiments, cell death models of ferroptosis were established with glutamate and erastin. As determined by MTT assay, fisetin improved the survival of cells with induced ferroptosis. The morphological alterations of ferroptotic cells were ascertained with a microscope. Fisetin similarly inhibited the changes in multiple ferroptosis-associated proteins induced by glutamate and erastin, reduced ROS and peroxidation products, and increased the level of antioxidants. In conclusion, fisetin exerts neuroprotective effects in TBI through multiple pathways, thereby alleviating tissue damage and cognitive dysfunction.

Cognitive impairment has become a major public health problem. Growing evidence suggests that high-fat diet (HFD) can cause cognitive dysfunction and increase the risk of dementia. However, effective treatment for cognitive impairment is not available. Ferulic acid (FA) is a single phenolic compound with anti-inflammatory and antioxidant properties. Nevertheless, its role in regulating learning and memory in HFD-fed mice and the underlying mechanism remains unclear. In this study, we aimed to identify the neuroprotective mechanisms of FA in HFD induced cognitive impairment. We found that FA improved the survival rate of HT22 cells treated with palmitic acid (PA), inhibited cell apoptosis, and reduced oxidative stress via the IRS1/PI3K/AKT/GSK3β signaling pathway; Furthermore, FA treatment for 24 weeks improved the learning and memory of HFD-fed mice and decreased hyperlipidemia. Moreover, the expression of Nrf2 and Gpx4 proteins were decreased in HFD-fed mice. After FA treatment, the decline of these proteins was reversed. Our study showed that the neuroprotective effect of FA on cognitive impairment was related to the inhibition of oxidative stress and apoptosis and regulation of glucose and lipid metabolism. These findings suggested that FA can be developed as a potential agent for the treatment of HFD-induced cognitive impairment.

BACKGROUND:Posterior interosseous nerve (PIN) entrapment syndrome is one of the causes of weakness and pain of the arm muscles, which is prone to missed diagnosis and misdiagnosis in clinic practice. This paper reports a case of PIN entrapment syndrome, with PIN injury indicated by electrophysiology. Musculoskeletal ultrasound was applied to identify that the entrapment point was located at the inlet of the Frohse arch and the outlet of the supinator muscle. Treatment with ultrasound-guided nerve hydrodissection was performed on the entrapment point, which significantly improved the symptoms. Ultrasound-guided nerve hydrodissection is an effective therapeutic method for PIN entrapment syndrome.CASE SUMMARY:A male patient, 35 years old, worked as an automobile mechanic. He felt slightly weak extension activity of his right fingers 2 years ago but sought no treatment. Later, the symptoms gradually became aggravated and led to finger drop, particularly severe in the right middle finger, accompanied by supination weakness of the right forearm. Neural electrophysiological examination showed that the patient had partial PIN injury of the right radius. Musculoskeletal ultrasound examination indicated PIN entrapment at the inlet of the Frohse arch and the outlet of the supinator muscle. Therefore, PIN entrapment syndrome was diagnosed. After treatment with ultrasound-guided nerve hydrodissection around the entrapment point, the dorsiflexion weakness of the right hand was significantly improved compared with before treatment.CONCLUSION:Ultrasound-guided hydrodissection is efficacious for PIN entrapment syndrome, with high clinical value and great application prospects.

腓总神经卡压综合征是指腓总神经及其主要分支受压引起的小腿外侧及足背感觉障碍,伸、伸趾、足背伸、足内外翻障碍,腓总神经完全性损伤的病人足下垂行走时呈跨越步态 [1].腓总神经卡压在临床上多见于腓骨头、颈处骨折,下肢不良姿势,石膏、夹板压迫及体位性神经损伤、腘窝外侧软组织损伤等.腓总神经卡压的治疗关键是对因治疗,尽早解除神经压迫.而传统的非手术治疗如口服糖皮质激素、改善循环、营养神经及热敷、理疗等,并不能直接解除对神经的压迫,且疗效慢 [2].手术行腓总神经探查松解治疗则创伤大,花费高,对病人的局部可能会造成二次损伤 [2].因此,近年来针对腓总神经卡压的治疗,需要寻找一种创伤小、疗效显著、且操作简便的技术方法.

目的:探讨丰富环境(environmental enrichment,EE)对重复轻度创伤性脑损伤(repetitive mild traumatic brain in-jury,rmTBI)小鼠学习、记忆功能和海马组织神经细胞再生的影响.方法:60只雄性C57BL/6小鼠随机分为3组:普通环境-假手术组(NC-sham组)、普通环境-脑损伤组(NC-TBI)和丰富环境-脑损伤组(EE-TBI) (n=20/group).根据前期研究中探索的rmTBI模型建立方法,对脑损伤组(EE-TBI和NC-TBI)小鼠进行重复轻度创伤性脑损伤造模,假手术组只予相应天数、次数的麻醉,不予损伤;造模前3天及造模后4周内,丰富环境组小鼠被安置在具有大空间、玩具、探险、运动器械、水食充足的丰富环境中;普通环境组小鼠置于水食充足、小笼饲养的普通环境;造模4周后,通过Morris水迷宫实验(morris water maze,MWM)进行行为学测试,分析比较各组小鼠学习和空间记忆等行为学差异;取小鼠海马组织,通过免疫组化法,检测分析各组小鼠海马DG区Doublecortin(DCX)的表达差异.结果:与假手术组小鼠相比,重复轻度脑损伤后,小鼠逃避潜伏期延长,60s内穿越平台次数减少,学习与记忆能力减退(均P＜0.05);与普通环境中的脑损伤小鼠相比,丰富环境中的脑损伤小鼠学习能力和记忆力增强(P＜0.05);与假手术组相比,重复轻度脑损伤后小鼠海马DG区DCX蛋白表达显著降低(P＜0.01),丰富环境可显著升高脑损伤后海马组织DCX蛋白的表达(P＜0.05).结论:重复轻度创伤性脑损伤后,丰富环境可有效改善小鼠的学习和空间记忆能力,并增加海马DG区神经细胞的再生.

目的:利用肌骨超声诊断技术探索脑卒中后偏瘫肩痛的病因组成特点,并探讨超声引导下注射治疗对脑卒中偏瘫肩痛的康复治疗效果.方法:选取2018年7月至2019年6月广西壮族自治区人民医院脑卒中后偏瘫肩痛患者50例,利用肌骨超声技术进行诊断,分析脑卒中偏瘫肩痛的病因及临床特点,选择其中30例作为观察组,行超声引导下靶向药物注射治疗.另选取30例脑卒中偏瘫肩痛并接受常规康复诊疗患者30例作为对照组.比较两组患者的疼痛程度变化、肩关节活动度、运动功能评定及日常生活能力(ADL).结果:50例脑卒中后肩痛患者中,肱二头肌长头肌腱炎症(50％)及肩峰—三角肌下滑囊炎症(48％)占比最高.与对照组比较,经超声引导下注射治疗后,观察组视觉模拟评分(VAS)、简式Fugl-Meyer运动功能评分(FMA-U)、改良Barthel指数(MBI)及肩关节活动度均明显改善(P＜0.05).结论:利用肌骨超声技术诊断及治疗可显著提高脑卒中后肩痛的诊断率,超声引导下康复治疗可有效缓解患者肩部疼痛,提高偏瘫上肢功能,改善ADL.

近年来脑卒中发病率逐年升高,病死率和致残率较高,其中肌痉挛是脑卒中最常见的并发症之一.肌痉挛处理的好坏直接关系到脑卒中患者的预后,其治疗一直是康复领域研究和关注的焦点,目前临床上治疗脑卒中后肌痉挛的方法有多种,效果各异.该文就近年来临床上对治疗脑卒中后肌痉挛的研究进展进行综述.

吞咽障碍为脑卒中后常见的并发症,严重影响患者的生活质量,然而,到目前为止,该病的治疗仍然缺乏特异性手段,现代医学常以鼻饲以及肠外营养等维持治疗.近年来研究表明,康复联合针灸治疗卒中后吞咽障碍有着很好的疗效.

目的 观察针刺治疗青少年偏头痛的临床疗效及其对血清降钙素基因相关肽(CGRP)、5-羟色胺及P物质水平的影响.方法 将94例青少年偏头痛患者随机分为针刺组和对照组,每组47例,针刺组采用中医针刺治疗;对照组给予常规药物治疗,两组疗程均为8周.观察两组治疗前后头痛症状学积分、血清CGRP、5-羟色胺及P物质水平及大脑前、中、后动脉(ACA、MCA、PCA)血流速度变化,观察两组临床疗效及不良反应发生率.结果 治疗后两组血清CGRP、P物质水平均低于治疗前,血清5-羟色胺水平高于治疗前(P<0.05).治疗后两组ACA、MCA血流速度均较治疗前减慢(P<0.05),但两组患者MCA、ACA、PCA血流速度比较差异无统计学意义(P>0.05).治疗后两组患者症状积分明显低于治疗前(P<0.05),但两组间症状积分、疗效比较差异均无统计学意义(P>0.05),观察组不良反应发生率低于对照组(P<0.05).结论 针刺或药物治疗青少年偏头痛的临床疗效相当,但针刺治疗安全性高,不良反应发生率低.

Studies suggest that microRNA (miR)‑34c may serve a role in cognitive function in rodent and primate groups. A previous study demonstrated an increase in miR‑34c expression in chronic epileptic rats with memory disorders, induced by pentylenetetrazol (PTZ). However, the mechanism underlying the effects of miR‑34c on cognitive function in epileptic rats remains unclear. Therefore, the present study investigated alterations in cognitive function in temporal lobe epileptic rats, induced by repeated injections of PTZ, following treatment with an miR‑34c agomir compared with a scramble group. Increased expression of miR‑34c was observed in the agomir group, in addition to an increased deficit in learning and memory function in the Morris water maze test. Glutamate receptor ionotropic N‑methyl‑D‑aspartate (NMDA) 2B (NR2B), phosphorylated (p)‑reduced nicotinamide‑adenine dinucleotide phosphate‑dependent diflavin oxidoreductase 1 (NR1) and p‑glutamate receptor 1 (GluR1) protein expression was detected in the hippocampus using western blotting. Additionally, the downregulation of NR2B, p‑NR1 and p‑GluR1 in the miR‑34c agomir group demonstrated that miR‑34c may serve a negative role in cognitive function in epileptic seizures, by dysregulating NMDA and α-amino-3-hydroxy-5‑methyl‑4‑isoxazolepropionic acid receptors, which are associated with long‑term potentiation.

Objective: Our group has previously reported the role of P38 mitogen-activated protein kinase (MAPK) pathway in the memory impairment of pentylenetetrazole (PTZ)-kindled rats. However, any contribution of p38 MAPK pathways to the cognitive dysfunction of PTZ-kindled rats remains unclear. The objective of this study is to verify the relationship between p38 MAPK pathway and cognitive function of epileptic rats, and discuss probable mechanisms.Methods: Thirty male SD rats were divided into three groups, namely, PTZ, inhibitor, and sham groups. All rats except those from the sham group were treated with PTZ to establish temporal lobe epilepsy (TLE) models, whereas the P38 MAPK inhibitor SB 203580 was given to the inhibitor group. Morris water maze test was performed to assay their learning and memory abilities. The levels of phosphorylated p38 (p-p38) and caspase 3 were confirmed using Western blot.Results: In the probe test of water maze, the PTZ group had the longest escape latency and least time to pass through the platform. Compared with the PTZ group, the inhibitor group had better performance in escape latency and spatial probe tests. Performance in the water maze test corresponded with the level of p-p38 and caspase 3 in hippocampus. We also found that the down-regulation of p-p38 in the inhibitor group led to down regulated levels of caspase 3.Conclusions: P38 MAPK pathway contributed to cognitive damage in PTZ-induced epilepsy via apoptosis cascade.

MicroRNA (miRNA) is believed to play a crucial role in the cause and treatment of epilepsy by controlling gene expression. However, it is still unclear how miRNA profiles change after multiple prolonged seizures and aggravation of brain injury in chronic epilepsy (CE). To investigate the role of miRNA in epilepsy, we utilized the CE rat models with pentylenetetrazol (PTZ) and miRNA profiles in the hippocampus. miRNA profiles were characterized using miRNA microarray analysis and were compared with the rats in the sham group, which received 0.9% physiological saline treatment at the same dose. Four up-regulated miRNAs (miR-139-3p, -770-5p, -127-5p, -331-3p) and 5 down-regulated miRNAs (miR-802-5p, -380-5p, -183-5p, -547-5p, -344a/-344a-5p) were found in the CE rats (fold change >1.5, P<0.05). Three of the dysregulated miRNAs were validated by quantitative real-time polymerase chain reaction, which revealed an outcome consistent with the initial results of the miRNA microarray analyses. Then, miR-344a agomir was intracerebroventricularly injected and followed by PTZ induction of CE models to investigate the effect of miR-344a in chronic neocortical epileptogenesis. After miRNA-344a agomir and scramble treatment, results showed a restoration of seizure behavior and a reduction in neuron damage in the cortex in miRNA-334a agomir treated rats. These data suggest that miRNA-344a might have a small modulatory effect on seizure-induced apoptosis signaling pathways in the cortex.

Objective To explore the effect of let-7c-1 on the learning and memory of PTZ-induced epileptic rats and its relevant mechanism.Methods A model of temporal lobe epilepsy (TLE) was induced via PTZ kindling in SD male rats.The epileptic rats were divided into epilepsy group,agomir-control group,let-7c-1 agomir group (12 rats for each).Twelve rats were served as a negative control group.The behavior and the expression levesl of let-7c-1,Bcl-2 protein and Caspase3 were evaluated at 28 days following PTZ.Results Compared to the negative group,the escape latency of epilepsy group was prolonged and the crossing times as well as the quadrant total distance in the target were reduced (P＜0.05).However,those parameters were not significantly different between the epilepsy group and the agmoir-control group (P＞0.05).Compared to the agmoir-control group,the escape latency of let-7c-1 agomir group was prolonged and the crossing times as well as the quadrant total distance in the target were reduced (P＜ 0.05).The expression levels of let-7c-1 and let-7c-1 were 1.35±0.32 in agmoir-control group and 62.53±21.01 in agomir group (F=50.97,P＜0.05).The expression levels of let-7c-1 were higher in let-7c-1 agomir group than in other groups (P＜0.05).Compared to the negative group,the expressions of Bcl-2 protein in other groups were decreased (P＜0.05) and the Caspase3 protein were increased (P＜0.05).Compared to the agomir-control group,the expression of Bcl-2 protein was significantly decreased and the expression of Caspase3 protein was significantly increased in let-7c-1 agomir group (P＜0.05).Conclusions The present study shows that let-7c-1 may impair the learning and memory of PTZ-induced epileptic rats through decreasing the Bcl-2 protein and increasing Caspase3 protein in the hippocampus.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS).Microglia are the resident innate immune cells in the CNS; they play an important role in the processes of demyelination and remyelination in MS.Microglia can function as antigenpresenting cells and phagocytes.In the past, microglia were considered to be the same cell type as macrophages, and researchers have different opinions about the role of microglia in MS.This review focuses on the original classification of microglia and their role in the pathogenesis of MS.Moreover, we present a hypothetical model for the role of microglia in the pathogenesis of MS based on recent findings.

AIMS:Amyloid β (Aβ) is considered to be an important mediator of the development and progression of Alzheimer's disease (AD). Its direct binding to p75(NTR), not TrkA, induces apoptosis, which is thought to be the most relevant feature of p75(NTR) regarding AD. In the present study we explored the regulation of p75(NTR) on Aβ production and accumulation during AD pathology. MATERIALS AND METHODS:We generated Tg2576/p75(NTR+/-) mice by crossing the transgenic AD mice (Tg2576) with p75(NTR-/-) mice to lower the p75(NTR) level. Under these conditions, we evaluated cognitive function using the Morris water maze, pathology and process by which two types of Aβ (Aβ40 and Aβ42) are produced, by enzyme-linked immunosorbent assay and Western blotting. KEY FINDING:The results showed that cognitive deficits were rescued in Tg2576/p75(NTR+/-) mice compared with those in Tg2576 mice. This cognitive functional recovery may be a consequence of a reduction in Aβ accumulation through the inhibition of β- and γ-secretase activities, without altering α-secretase activity. SIGNIFICANCE:Here, we investigated the mechanism by which p75(NTR) regulates Aβ production and accumulation. Better understanding the relationship between p75(NTR) and Aβ producing may help taking insight into the AD pathology.

The down-regulation of microRNA-328a (miR-328a) in pentylenetetrazole (PTZ)-kindled rats with memory impairment was demonstrated in our previous study, while any contribution of miR-328a to cognitive dysfunction of PTZ-kindled rats remains unknown. In this study we have investigated the effect and the underlying mechanism of miR-328a on the cognitive function in PTZ-kindled rats. 48 SD male rats were divided into 4 groups as follows: a PTZ kindled group, a miR-328a antagomir group, an antagomir-control group, and a sham group (n=12 for each). All rats except those from the sham group were treated with PTZ 14 times at intervals of 48h to establish the temporal lobe epilepsy (TLE) models, and miR-328a antagomir was given to the antagomir group as a treatment by lateral-ventricle injection the day after the first injection of PTZ. Morris water maze (MWM) test was performed to assay their learning and memory abilities. The down-regulation of miR-328a in the PTZ group was confirmed using RT-qPCR and the expression of miR-328a was diminished after antagomir treatment (P<0.05). In the probe test of water maze, the time and distance of the PTZ group were both shorter than those of the sham group (P<0.05), and those of the antagomir-control group were both longer than those of the antagomir group (P<0.05). In addition, we found that with the down-regulation of miR-328a, the levels of Beta-site APP-cleaving enzyme (BACE), which is a bioinformatics-predicted target of miR-328a, were up-regulated. These findings suggest that miR-328a may play a role in memory dysfunction in PTZ-kindled rats by regulating the BACE levels and this links the PTZ model with Alzheimer's disease.

Our previous study showed that the expression of miR-181a in memory impairment group of pentylenetetrazol (PTZ)-induced epileptic rats was up-regulated, but whether miR-181a influenced the cognitive function of PTZ-induced epileptic rats remains unknown. Therefore, we investigated the role of miR-181a in the cognitive function of PTZ-induced epileptic rats. A model of temporal lobe epilepsy (TLE) was induced via PTZ kindling in SD male rats. The epileptic rats were divided into Epilepsy group, Agomir-control group, miR-181a agomir group, 12 rats for each. 12 rats were used as sham group. We found that compared to the sham group, the expression of miR-181a in the Epilepsy group was increased. We also found that escape latency in the 5th day was prolonged and crossing times in the 6th day was reduced via Morris Water Maze test, which may indicate memory impairment. Furthermore, overexpression of miR-181a effectively reduced Bcl-2 protein level and increased apoptosis in hippocampus. Moreover, compared with Agomir-control group, the escape latency of miR-181a agomir group was obviously induced (P < 0.05). Our findings suggest that miR-181a may play a role in impairing the cognitive function of PTZ-induced epileptic rats, and miR-181a could decrease the Bcl-2 protein and induce the apoptosis in the hippocampus that might be the way to impair cognitive function.

目的 通过测定海人酸(kainic acid,KA)致痫大鼠不同时间点脑脊液及脑组织中白蛋白、S100B蛋白及胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)表达量,探讨白蛋白、S100B蛋白和GFAP表达量变化与癫痫的关系.方法 经SD大鼠侧脑室注射KA制备癫痫大鼠模型,对照组注射生理盐水.各模型组于造模后6h、24 h、3d和7d四个时间点,对照组于注射生理盐水后6h,分别采用ELISA方法测定脑脊液白蛋白和S100B蛋白水平,以免疫组化法检测脑组织中白蛋白、S100B和GFAP表达,HE染色观察海马CA3区细胞及结构变化.结果 (1)脑脊液:模型组6h时白蛋白水平高于对照组(P＜0.05),模型组其余时间点与对照组比较差异均无统计学意义(均P＞0.05);其中,模型组7d、3d时白蛋白水平低于6h时(均P＜0.05).模型组6h、24 h、3d和7d4个时间点脑脊液S100B水平均高于对照组(均P＜0.05);模型组4个时间点间两两比较差异均有统计学意义(均P＜0.05),其中以模型组3d时最高.(2)脑组织:模型组24 h及模型组6h侧脑室室管膜白蛋白表达均高于对照组(均P＜0.05),3d和7d时与对照组比较差异无统计学意义(P＞0.05);模型组四个时间点两两比较,模型组3d、7d时均低于模型组6 h(P＜0.05),模型组7d时亦低于其他2个模型组(均P＜0.05).模型组4个时间点海马区S100B表达均高于对照组(均P＜0.05);模型组四个时间点两两比较,模型组24 h、3d和7d时均高于模型组6h时(P＜0.05),且模型组7d时低于模型组3d时(P＜0.05).模型组3d、7d时海马区GFAP表达均高于对照组(均P＜0.05),其余时间点与对照组比较差异无统计学意义(P＞0.05);模型组四个时间点两两比较,模型组3d、7d时均高于模型组24 h与6h时(均P＜0.05),且7d时亦高于3d时(P＜0.05).(3)HE染色显示,模型组6h时海马CA3区神经元排列紊乱、分散,细胞多形性改变,部分细胞核深染;24 h时细胞由圆形改变为多形性改变;3d和7d时,核深染的细胞数增加,细胞排列层次减少、紊乱,细胞坏死.结论 癫痫发作后脑脊液中白蛋白、S100B及脑组织中白蛋白、S100B及GFAP表达增高.

Previous studies have demonstrated a close relationship between abnormal regulation of microRNA (miRNA) and various types of diseases, including epilepsy and other neurological disorders of memory. However, the role of miRNA in the memory impairment observed in epilepsy remains unknown. In this study, a model of temporal lobe epilepsy (TLE) was induced via pentylenetetrazol (PTZ) kindling in Sprague-Dawley rats. First, the TLE rats were subjected to Morris water maze to identify those with memory impairment (TLE-MI) compared with TLE control rats (TLE-C), which presented normal memory. Both groups were analyzed to detect dysregulated miRNAs in the hippocampus; four up-regulated miRNAs (miR-34c, miR-374, miR-181a, and miR-let-7c-1) and seven down-regulated miRNAs (miR-1188, miR-770-5p, miR-127-5p, miR-375, miR-331, miR-873-5p, and miR-328a) were found. Some of the dysregulated miRNAs (miR-34c, miR-1188a, miR-328a, and miR-331) were confirmed using qRT-PCR, and their blood expression patterns were identical to those of their counterparts in the rat hippocampus. The targets of these dysregulated miRNAs and other potentially enriched biological signaling pathways were analyzed using bioinformatics. Following these results, the MAPK, apoptosis and hippocampal signaling pathways might be involved in the molecular mechanisms underlying the memory disorders of TLE.