度洛西汀和氟西汀对抑郁模型大鼠 S100B、ERK1/2－NF－κB 表达的影响

目的：比较度洛西汀和氟西汀对抑郁模型大鼠海马 S100B、ERK1/2－NF－κB 表达的影响.方法慢性轻度不可预知应激刺激法制备54只抑郁症模型大鼠,随机分为非干预组(B 组)、度洛西汀干预组(C 组)、氟西汀干预组(D 组),各18只.另外选取18只大鼠为对照组(A 组).各组灌胃[A组和 B 组(生理盐水),C 组(度洛西汀)、D 组(氟西汀)]28 d 后,应用糖水偏爱试验和旷场试验检测大鼠行为学改变.Western blot 检测各组海马 S100B、ERK1/2和 NF－κB 的表达.结果灌胃28 d 后 B 组糖水消耗率(43±15)％显著较 A、C、D 组低[(63±11)％,(67±6)％,(61±10)％](P ＜0．05). C 和 D组大鼠干预28 d 后旷场试验水平评分、垂直运动评分与潜伏期分别为(70．66±11．53)分和(67．54±10.08)分,(20．32±8．85)分和(21．34±7．46)分,(1．0±0．4)s 和(1．1±0．3)s,与 A 组(71．19±12．08)分,(20．42±8．76)分,(1．01±0．3)s 比较,差异均无统计学意义(P ＞0．05);C、D 组与 B 组比较,水平运动评分和垂直运动评分升高,潜伏期降低.A、C、D 组大鼠海马 S100B、ERK1/2、NF－κB 表达显著高于 B组(P ＜0．05),C 和 D 组差异无统计学意义.结论度洛西汀和氟西汀均能够改善抑郁模型大鼠的行为能力及上调海马 S100B、p－ERK1/2－NFκB 表达水平,但度洛西汀和氟西汀对相关因子表达的影响无差异.     

单唾液酸四己糖神经节苷脂对缺氧缺血性脑病患儿血清NSE S-100B的影响

目的探讨单唾液酸四己糖神经节苷脂(GM1)对缺氧缺血性脑病(HIE)患儿血清NSE、S-100B水平的影响及其作用机制。方法随机选择产科同期出生1d的健康足月新生儿20例作对照组,将40例HIE患儿随机分为常规治疗组(20例)和GM1治疗组(20例),GM1治疗组在常规治疗基础上于生后第2天加用GM1静滴,20mg/d,连续用药7d。常规治疗组进行常规治疗。3组新生儿均于生后第1天(治疗前)、第8天(治疗后)时采集血液标本,采用双抗体夹心ABC-ELISA法进行血清NSE、S-100B的检测。结果治疗前,2组HIE患儿血清中NSE、S-100B的水平高于正常新生儿(P<0.01);常规治疗组与GM1治疗组血清NSE、S-100B水平比较,差异无统计学意义(P>0.05)。2组第8天血清NSE、S-100B水平均低于第1天(P<0.01)。治疗后,HIE患儿血清中NSE、S-100B水平高于正常对照组(P<0.01)。GM1治疗组血清NSE、S-100B水平下降率大于常规治疗组(P<0.01)。结论 HIE患儿脑组织中神经元和神经胶质细胞均有不同程度的损伤,动态检测血清NSE、S-100B水平,可能有助于HIE的早期诊断和判断HIE脑损伤的修复程度,GM1对神经元及神经胶质细胞均有修复作用。     

硫酸镁对重症手足口病患儿血清神经元特异性烯醇化酶的影响

目的研究硫酸镁对重症手足口病患儿血清神经元特异性烯醇化酶(NSE)的影响。方法选取2016-03—12郑州儿童医院重症监护室收治的重症手足口病伴血清NSE异常且处于急性期的患儿100例为研究对象,采用随机数字表法分为对照组和治疗组(A、B、C组),每组25例,均常规给予抗病毒、抗感染、对症等常规治疗,对照组给予神经节苷脂2 mL/d,A组给予小剂量硫酸镁[40 mg/(kg·d)],B组给予大剂量硫酸镁[80 mg/(kg·d)],C组给予神经节苷脂(2 mL/d)联合小剂量硫酸镁[40 mg/(kg·d)],7 d为1个疗程。对比4组治疗7 d后临床疗效,以及治疗前、治疗3 d、治疗7 d血清NSE的变化。结果治疗7 d后,4组临床疗效比较差异无统计学意义(P0.05)。治疗前,4组血清NSE水平比较差异无统计学意义(P0.05)。治疗3 d、7 d,A、B、C组血清NSE较对照组降低,差异有统计学意义(P0.05);B、C组血清NSE降低水平较A组差异有统计学意义(P0.05)。4组治疗7 d血清NSE下降水平比较,差异有统计学意义(P0.05)。结论硫酸镁可有效降低重症手足口病患儿血清NSE,有较好的脑保护作用,对病情的转归有积极作用。     

神经节苷脂对缺血再灌注大鼠的脑保护作用

目的 探讨神经节苷脂对缺血再灌注大鼠脑组织的保护作用.方法 建立大鼠大脑中动脉栓塞再灌注模型, 采用磁共振弥散加权成像(DWI)与磁共振波谱(MRS)技术,分别对假手术组、缺血再灌注组、神经节苷脂组大鼠的脑梗死体积、氮-乙酰天门冬氨酸(NAA)及乳酸(Lac)等代谢产物进行比较.结果 神经节苷脂组在缺血再灌注1 h、3 h、6 h时梗死区体积分别为(30.32±8.18)mm3、(35.17±12.45)mm3、(31.4±8.56)mm3,缺血再灌注组分别为(204.6±37.77)mm3、(218.9±67.33)mm3、(213.4±99. 95)mm3,两组各时间点比较差异有统计学意义(均P<0.01).神经节苷脂组在缺血再灌注1 h、3 h、6 h Lac/磷酸肌酸和肌酸(PCr Cr)比值分别为0.09±0.11、0.15±0.18、0.13±0.22,缺血再灌注组分别为1.09±0.34、0.99±0.37、1.16±0.27,两组各时间点比较差异有统计学意义(均P<0.01);神经节苷脂组在缺血再灌注1 h、3 h、6 h NAA /(PCr Cr)比值分别为1.04±0.38、 0.81±0.21、0.77±0.25,缺血再灌注组分别为0.55±0.23、0.57±0.12、0.58±0.13,各时间点两组比较差异有统计学意义(均P<0.01).结论 神经节苷脂通过抑制Lac的生成来间接减少Lac所导致的神经元细胞毒性脑水肿,从而显示其具有显著的脑保护作用.     

β-淀粉样蛋白诱导海马神经元自噬通路启动及二苯乙烯苷的干预

目的 探讨在阿尔茨海默病(AD)脑损伤中,β-淀粉样蛋白(Aβ)神经毒性对大鼠行为学、自噬相关蛋白Beclin-1和LC3-Ⅱ的影响及何首乌提取物二苯乙烯苷(TSG)的干预作用.方法 选Wistar大鼠80只,随机数字表法分为对照组、假手术组、模型组、TSG组,各20只.采用立体定向仪下于海马部位注射微量Aβ1-42造模,Y电迷宫及Moms水迷宫检测行为学变化,反转录聚合酶链反应及Western blot法检测制模后第21天海马神经元内自噬相关蛋白Beclin-1和LC3 -Ⅱ的mRNA及蛋白表达变化.结果 在模型组中,大鼠Y电迷宫躲避所需的电刺激次数增加,Morris水迷宫测试中潜伏期延长,游泳路程增加及穿越平台次数减少;Beclin-1和LC3-Ⅱ的mRNA及蛋白的表达一致,在21 d时,模型组Beclin-1蛋白(0.51±0.03),LC3-Ⅱ蛋白(0.68 ±0.04)与对照组(0.31±0.01、0.31±0.02)比较,差异有统计学意义(t=28.2843、37.0000,均P＜0.05);TSG干预后,大鼠躲避所需的电刺激次数减少,潜伏期缩短,游泳路程缩短,穿越平台次数增加;Beclin-1和LC3-Ⅱ蛋白表达强度较模型组减弱,差异有统计学意义(t=9.8387、16.2698,均P＜0.05).结论 海马神经元在受到Aβ刺激后,可上调自噬蛋白Beclin-1和LC3-Ⅱ因子表达,启动自噬通路;TSG可通过减轻内质网应激损害,下调Beclin-1和LC3-Ⅱ的表达来抵抗Aβ的神经毒性,改善大鼠行为学表现,发挥脑保护作用.     

mNGF联合神经节苷脂治疗HIE对脑血流灌注及外周血S-100β Caspase3和mIL-2R表达的影响

目的探讨鼠神经生长因子(mNGF)联合神经节苷脂治疗缺氧缺血性脑病(HIE)的效果及对脑血流灌注、外周血S-100β、Caspase3和白介素-2受体(mIL-2R)表达的影响。方法选取郑州大学附属郑州中心医院2017-03—2018-02治疗的100例HIE患儿,随机分为观察组与对照组各50例,对照组给予神经节苷脂治疗,观察组在对照组的基础上联合使用mNGF,比较2组临床疗效、脑血流灌注水平以及外周血S-100β、Caspase3和mIL-2R表达水平。结果观察组临床有效率(90.00%)高于对照组(72.00%),差异有统计学意义(P0.05);观察组治疗后颈内动脉收缩期流速(Vs)水平高于对照组,外周血管阻力(RI)水平较对照组低,差异有统计学意义(P0.05);观察组治疗后S-100β、Caspase3水平低于对照组,外周血mIL-2R水平高于对照组,差异有统计学意义(P0.05);2组治疗期间均未出现严重不良反应。结论 mNGF联合神经节苷脂治疗HIE,可有效改善患儿脑血流灌注水平以及外周血神经元蛋白指标,提高外周血中mIL-2R表达率,效果显著,安全性较高。     

半乳糖凝集素-3在大鼠精神分裂症发病机制中的作用

目的探究半乳糖凝集素-3 (Galectin-3)介导的脑源性神经营养因子(brain-derived neurtrophicfactor,BDNF)/酪氨酸激酶受体B(tyrosine kinase receptor B,TrkB)通路在大鼠精神分裂症发病机制中的作用。方法将24只大鼠随机分为模型(M)组(n=12)和对照(C)组(n=12),使用MK-801诱导M组建立大鼠精神分裂症模型,C组给予等量生理盐水。1周后,采用旷场和强迫游泳实验评估大鼠行为变化,Morris水迷宫实验检测认知功能,免疫组化测定脑组织Galectin-3和BDNF表达,western blotting和RT-PCR法检测海马Galectin-3、BDNF和TrkB蛋白含量及mRNA水平变化。结果 M组大鼠和C组比较,穿越格数减少(23.25±3.09 vs. 55.25±6.13,P0.001),游泳不动时间延长[(122.50±6.95)s vs.(89.00±6.68)s,P0.001]。水迷宫实验显示M组逃避潜伏期时间高于C组[(26.36±4.62)s vs.(14.64±3.72)s],穿越平台次数也低于C组(2.75±0.96 vs. 8.25±1.26),差异均有统计学意义(P0.001)。M组大鼠海马区Galectin-3蛋白含量(0.83±0.04 vs. 0.34±0.05)及mRNA水平(3.79±0.82 vs. 1.02±0.12)较C组上调,BDNF与TrkB蛋白含量(0.40±0.05 vs. 0.77±0.04;0.24±0.06 vs. 0.52±0.06)及mRNA水平(0.46±0.09 vs. 1.01±0.07;0.37±0.04 vs. 1.02±0.24)降低,差异均有统计学意义(P0.05)。结论精神分裂症大鼠海马组织中Galectin-3高表达,精神分裂症BDNF/TrkB功能异常、海马神经元损伤可能与其过度表达有关。     

新生儿缺氧缺血性脑病S-100B与NSE的检测及临床意义

目的探讨新生儿缺氧缺血性脑病(HIE)血清S-100B与NSE的检测及临床意义。方法选取我院2013-01—2016-01收治的90例HIE患者为观察组,另选取同期健康新生儿30例为对照组。观察组根据病情程度分为轻度、中度与重度组,分别采用酶联免疫吸附(ELISA)法和电化学发光法测定研究对象各时期血清S-100B与NSE的水平,对比各组S-100B与NSE水平的变化情况。结果观察组血清S-100B与NSE水平明显高于对照组,差异有统计学意义(P0.05)。观察组各亚组血清S-100B与NSE水平比较,差异有统计学意义(P0.05),随着病情程度的加重,S-100B与NSE水平均呈升高趋势。动态监测显示,出生后1、3d,观察组S-100B与NSE含量逐渐升高,至第7天时S-100B与NSE含量降低(P0.05),血清S-100B与NSE浓度高峰出现于出生后第3天。结论临床检测S-100与NSE有助于HIE的早期诊断,且可作为判断HIE病情程度的敏感指标。     

神经节苷脂治疗新生儿缺氧缺血性脑病的有效性及安全性

目的：评价神经节苷脂治疗新生儿缺氧缺血性脑病（HIE）的有效性及安全性。方法随机抽取2012‐12—2013‐12我院住院治疗的54例新生儿缺氧缺血性脑病患者作为研究对象，按照随机双盲对照原则分为对照组和观察组，对照组主要采取综合治疗，观察组在综合治疗的基础上以神经节苷脂治疗，治疗后观察2组患者新生儿行为神经评分，并比较2组患者NSE、S100B水平。结果2组患者NBNA评分在治疗第10天逐渐出现差异，观察组患者较对照组NBNA评分高，治疗第28天2组NBNA评分差异增大；观察组患者较对照组血清NSE、S100B水平高，2组比较差异有统计学意义（P＜0.05）。结论神经节苷脂治疗 H IE临床效果良好，且无不良反应，是一种安全有效的治疗方法。     

Aβ诱导大鼠行为学障碍中内质网Aβ结合蛋白的表达及二苯乙烯苷的影响

目的 探讨在阿尔茨海默病(AD)脑损伤中,β淀粉样蛋白(Aβ)神经毒性对大鼠行为学障碍、内质网Aβ结合蛋白(ERAB)表达的影响及何首乌提取物二苯乙烯苷(TSG)的干预作用.方法 采用立体定向仪于海马部位注射微量Aβ1-42造模,Morris水迷宫检测行为学变化,免疫组化及免疫印迹法检测ERAB蛋白的表达变化.结果 模型组ERAB蛋白表达的增高,TSG干预后ERAB的表达低于模型组,差异有统计学意义.结论 海马神经元在受到Aβ刺激后,启动内质网自稳调节系统,可上调内质网ERAB表达,减少异常折叠的Aβ产生,对受损细胞产生保护作用;二苯乙烯苷可通过减少Aβ的毒性损害,下调ERAB的表达,发挥脑保护作用.     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Pediatric Epilepsy Surgery

Summary: The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the child's symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.