L—型Ca^2＋通道在马桑内酯致痫中的作用

以马桑内酯大鼠癫痫样行为发作、脑电图改变和离体海马脑片CA1区锥体细胞痫样放电为指标，观察L-型电压依赖性Ca2 通过阻断剂硝苯吡啶对其致痫作用的影响。结果发现：实验组与对照组相比较，大鼠癫痫发作推迟，程度减轻，脑电痫波出现潜伏期延长，波幅下降。离体海马脑片CA1区锥体细胞痫样放电被抑制，EPSP降低（P＜0．05）。结果提示，马桑内酯可能通过激活L-型电压依赖性Ca2 通道，使神经细胞内游离Ca2 增多而致痫。     

马桑内酯在大鼠离体海马脑片上引起的癫痫样放电活动

采用大鼠离体海马脑片技术,建立了马桑内酯(Coriaria lactone,CL)引起的海马CA 1区锥体细胞癫痫样放电活动模型,并初步探讨了CL的致痫作用机理,可能与直接影响锥体细胞固有爆发放电能力有关。     

DHPG和BMI诱导的癫痫样放电模型的建立及比较

目的在离体大鼠海马脑片上,通过激活Ⅰ型代谢型谷氨酸受体（mGluR）或阻断γ-氨基丁酸（GABA）受体,诱导癫痫样放电。方法将离体大鼠海马脑片暴露于Ⅰ型mGluR特异性激动剂对羟基苯甘氨酸（DHPG）或GABA．受体阻断剂荷包牡丹碱（BMI）,利用全细胞记录模式记录海马CA3区域单个锥体细胞的电活动。结果暴露于DHPG或BMI中的海马脑片CA3区域的锥体细胞均产生癫痫样放电,且两者的放电频率比较差异无统计学意义（P〉0．05）。结论在离体情况下,破坏神经兴奋性和抑制性系统的平衡可以诱导产生癫痫样放电活动。     

马桑内酯致痫大鼠大脑皮层及海马神经元钙离子活度的变化

大脑皮层或海马内注射马桑内酯可以引起大鼠癫痫样发作及脑电图痫样放电。应用钙离子选择性微电极测量了癫痫模型大鼠海马和皮层的钙离子活度的改变。皮层或海马内注射５μ马桑内酯（５ｍｇ／ｍｌ），３ｍｉｎ后观察到细胞外钙离子活度的明显改变，大脑皮层及海马内Ｃａ（２＋）分别下降了０．６１ｍｍｏｌ／Ｌ及０．７４ｍｍｏｌ／Ｌ，与马桑内酯注射前相比较，注射后皮层或海马内的Ｃａ（２＋）活度具有极显著差异（Ｐ＜０．０１）。马桑内酯注射后２０ｍｉｎＣａ（２＋）活度恢复至正常水平。上述结果表明马桑内酯注射后神经细胞群发生爆发性电活动时出现钙内流现象，海马脑片的实验结果与在体实验相似。     

桂枝对致痫大鼠海马CA1区诱发场电位的影响

目的 探讨桂枝对癫痫模型海马脑片诱发场电位的影响。方法 以毛果芸碱致痫大鼠为实验对象，用细胞外玻璃微电极记录方法，观察桂枝对癫痫模型离体海马脑片CA1区锥体细胞诱发群峰电位（population spike,PS）的影响。结果 桂枝提取液使致痫大鼠海马脑片PS幅度平均降低28.73%，平均16.8min恢复。结论 桂枝能降低致痫大鼠海马脑片CA1区顺向诱发PS幅度，提示桂枝对中枢神经系统的突触传递过程有明显的抑制效应。     

血管性痴呆大鼠海马区长时程增强变化的研究

目的 观察四血管阻断大鼠海马CA1区长时程增强（long-term potentiation,LTP)的变化，并探讨其可能机制。方法 改良Pulsinelli's四血管阻断法建立血管性痴呆大鼠模型；采用电脑控制的穿梭箱系统检测大鼠学习记忆；离体海马脑片诱导的CA1区LTP检测大鼠学习记忆电生理改变；透射电镜观察大鼠海马CA1区的超微结构改变。结果 脑缺血组大鼠AAR在2w时较对照组显著下降（P＜0．05），4w和2m时更加明显（P＜0．01）。对照组海马脑片可明显诱出LTP波形，脑缺血组各时相点均几乎诱不出LTP，条件刺激前后fEPSP斜率变化的百分数与对照组比较差别明显（P＜0．05）；但各时相点间无明显差别。脑缺血组海马CA1区神经元细胞核固缩，线粒体肿胀、颗粒减少、电子密度增高，轴突脱髓鞘，次级溶酶体形成，高尔基复合体扩张空泡、神经毡空泡等慢性缺血缺氧改变。结论 海马脑片CA1区LTP检测能够客观地反映大鼠短时记忆损害，是可靠的学习记忆细胞模型。     

血管性痴呆大鼠认知障碍的NMDAR机制研究

目的：观察四血管阻断（4VO）大鼠海观NMDA受体NMDAR的变化规律，探讨其在血管性痴呆（VD）形成中的作用机制，方法：改良的Pulsinelli 4VO法建立大鼠血管性痴呆模型，电脑控制的穿梭箱系统和离体海马脑片诱导的CA1区LTP检测大鼠学习记忆，原位杂交方法检测大鼠海马NMDAR1 mRNA的表达。结果：VD组大鼠的主动回避反应在2周时较对照组显著下降（P＜0．05），4周和2月时更加明显（P＜0．01），海马脑片长时程增强（LTP）的诱导出现明显障碍；VD组2周时CA1和CA3区NMDAR1 mRNA表达较对照组增高，DG区无明显改变；4周和2月时海马各区表达均减低。结论：大鼠海马区NMDAR与学习记忆有关，在脑缺血的早期表达增高介导了兴奋毒性作用；但在,缺血后期，NMDAR mRNA表达减低可能与学习记忆损害有关，为进一步进行NMDAR拮抗剂和激动剂治疗VD的研究提供了实验依据。     

DHPG和BMI诱导的癫痫样放电模型的建立及比较

目的 在离体大鼠海马脑片上,通过激活Ⅰ型代谢型谷氨酸受体(mGluR)或阻断γ-氨基丁酸(GABA)受体,诱导癫痫样放电.方法 将离体大鼠海马脑片暴露于Ⅰ型mGluR特异性激动剂对羟基苯甘氨酸(DHPG)或GABAA受体阻断剂荷包牡丹碱(BMI),利用全细胞记录模式记录海马CA3区域单个锥体细胞的电活动.结果 暴露于DHPG或BMI中的海马脑片CA3区域的锥体细胞均产生癫痫样放电,且两者的放电频率比较差异无统计学意义(P>0.05).结论 在离体情况下,破坏神经兴奋性和抑制性系统的平衡可以诱导产生癫痫样放电活动.     

Merlin蛋白在马桑内酯致痫大鼠颞叶皮层及海马CA1区的表达

目的探讨Merlin与颞叶癫痫海马硬化间的相互关系。方法采用马桑内酯慢性致痫大鼠模型,通过免疫组化方法观察Merlin在点燃组、未点燃组及对照组中颞叶皮层及海马CA1区的表达。结果在点燃组颞叶皮层及海马CA1区神经元Merlin的表达较未点燃组及对照组的表达有增多（P〈0．05）,而未点燃组与对照组之间在神经元表达上差异无统计学意义（P〉0．05）。各组在上述部位胶质细胞的表达均较少。结论Merlin在马桑内酯点燃大鼠模型颞叶皮层及海马CA1区神经元中的过度表达可能参与了神经元凋亡、海马硬化的过程。     

戊四氮致痫大鼠海马c-FOS蛋白表达及钙拮抗剂的影响

目的：探讨戊四氮（PTZ）致痫后大鼠的海马锥体细胞、齿状回颗粒细胞c-FOS蛋白表达情况，和钙拮抗剂尼莫地平对c-FOS蛋白表达的影响。方法：大鼠腹腔注射PTZ 60mg/kg建立急性癫痫动物模型，测定痫性发作潜伏期、发作强度，用免疫组化LSAB法检测2h和4h后c-FOS的表达。结果：对照组大鼠无癫痫发作，干预组痫性发作潜伏期较致痫组明显延长（P＜0．01），且发作强度明显减弱（P＜0．01）；对照组海马各区c-FOS仅低水平表达，致痫后表达明显增高（P＜0．01），干预组2h比致痫组2h的c-FOS阳性率明显降低（P＜0．01），4h干预组与致痫组无显著性差异（P＞0．05）。结论：大剂量PTZ可诱发大鼠全面阵挛发作，诱导海马锥体细胞、齿状回颗粒细胞c-FOS表达增高，海马结构涉及PTZ致痫引起阵挛发作的发展或传播的病理生理机制，尼莫地平可延缓癫痫的发生，减轻发作强度，降低c-FOS的表达。     

马桑内酯在大鼠离体海马脑片上引起的癫痫样放电活动

Coriaria lactone (CL) is an active constituent of a medicinal herb used as psychosolytic in traditional Chinese medicine. Recently it has been found that CL appears to act as a convulsant agent. Subsequently both acute and chronic epilepsy models caused by CL have been established successfully. In order to observe further the epileptogenic effects of CL in vitro, the hippocampal slice technique was used in experiments with 36 slices. The results are as follows: Addition of CL to the perfusion bathing the slices of rat hippocampus increased evoked-response in body layer of CA1 in a dose-dependent manner, and induced epileptiform burst. CL augmented population spike of CA1 pyramidal neurons triggered by either orthodromic stimulus (through synapses) or antidromic stimulus (direct effect on the axon of CA1 pyramidal cells) without alteration of presynaptic fiber volley and field-EPSP, and there was no significant change in latency of burst. Finally GABA had a weak effect on CL-induced epileptiform activity. These observations suggest that CL probably has a direct effect on the soma of pyramidal neurons, CL-induced epileptiform burst may be a result of altering the innate capacity of burst and increasing the intrinsic excitability of pyramidal cell membranes.     

N-甲基-D-天门冬氨酸诱导Wistar乳鼠癫痫发作West综合征动物模型的初步探讨

目的:探讨NMDA诱发Wistar乳鼠惊厥发作的表现及皮质脑电图特点和建立West综合征动物模型的可能性。方法:选用12日龄Wistar乳鼠系统地进行腹腔注射NMDA诱导癫痫发作,对其痫性发作的类型、潜伏期、发病率及行为改变和皮质脑电图变化作以相应记录。结果:12~13日龄的Wistar乳鼠引出甩尾等自动症及前弓反张发作,14～25日龄的Wistar乳鼠只有自动症而没有前弓反张发作。对照组皮质脑电图无明显癫痫性波形发放,仅可见偶发棘波,NMDA处理组则在自动症及惊厥发作期间出现某些特征性改变。对照组及NMDA处理组在组织形态学方面未见明显异常改变。结论:NMDA可以诱导Wistar乳鼠产生一种独特的、年龄依赖性癫痫发作,虽未满足West综合征动物模型的全部标准,但发作表现和脑电图改变与儿童时期West综合征有相似之处。     

Electrocorticography-Guided Surgical Treatment of Solitary Supratentorial Cavernous Malformations with Secondary Epilepsy

Objective To evaluate the efficacy of electrocorticographic（ECoG） monitoring and the application of different surgical approaches in the surgical treatment of solitary supretentorial cavernous malformations with secondary epilepsy. Methods This study enrolled a consecutive series of 36 patients with solitary supratentorial cavernous malformations and secondary epilepsy who underwent surgery with intraoperative ECoG monitoring in the Department of Neurosurgery between January 2004 and January 2008. The patients were composed of 15 males and 21 females, aged between 8 and 52 years（mean age 27.3±2.8 years） at the time of surgery. Epilepsy history, the type of epilepsy at the presentation, lesion location, the incidence of residual epileptiform discharges, and postoperative outcomes were evaluated. Results Histopathological examination indicated cavernous malformations and hippocampal sclerosis in 36 and 5 cases, respectively. Neuronal degeneration, glial cell proliferation, and neurofibrillary tangles were found in all the resected cerebral tissues of extended lesionectomy of residual epileptic foci. Lesionectomy, anterior temporal lobectomy, anterior temporal lobectomy plus cortical thermocoagulation, extended lesionectomy, extended lesionectomy plus cortical thermocoagulation were performed in 4, 4, 1, 14, and 13 cases, respectively. Residual epileptiform discharges were captured in 9 out of the 14 patients who had additional cortical thermocoagulation. According to Engle class for postoperative outcomes, 27 cases were class I（75.00%）, 5 were class II（13.89%）, 2 were class III（5.56%）, and 2 were class IV（5.56%）, thus the total effective rate（class I＋class II） was 88.89%. Neither of epilepsy history, the type of epilepsy, and the location of cavernous malformation was significantly related to outcomes（P〉0.05）. A significant relationship was found between the incidence of residual epileptiform discharges and outcomes（P=0.041）. Conclusions Intraoperative ECoG monitoring, the a     

The Effect of Coriaria Lactone on NMDA Receptor Mediated Currents in Rat Hippocampal CAI Neurons

To investigate the exact mechanism of epileptogenesis induced by coriaria lactone (CL), the effect of CL on NMDA receptor mediated current (Iasp) in rat hippocampal CAI neurons was investigated by using nystatin perforated whole-cell patch clamp. 10-6-10-4 mol/L Asp acted on NMDA receptors and elicited an inward current (Iasp) at a holding potential (VH) of -40mV in presence of 10-6 mol/L glycine and absence of Mg2+ extracellularly. CL enhanced NMDA receptor mediated current induced by Asp, but had no effect on threshold concentration, EC50,Hill coefficient as well as maximal-effect concentration and reversal potential of Iasp. The effect had no relationship with holding potential. These results showed that CL could enhance NMDA receptor mediated current to increase [Ca2+]I of neurons by acting on Gly site, thereby inducing epilepsy.     

ACTH和吗啡对创伤痛大鼠海马锥体神经元NMDA受体通道的抑制

目的 探讨创伤痛大鼠海马锥体神经元NMDA受体通道动力学特性的变化ACTH和吗啡的作用。方法 实验以双侧踝关节离断大鼠为创伤痛模型，应用细胞贴附式膜片钳技术。结果 在正常7－10d大鼠急性分离的海马CA1区锥体神经元上，记录到多数膜下的NMDA受体通道有两个电导水平，分别为50pS及38pS,以50pS占多数，且以短开放为主，但也有长开放通道。38pS电导仅有短开放通道。大鼠双侧踝关节完全离断后2h,50pS有38pS短开放通道，50pS长开放通道的开放概率和开放时间均比正常对照组显著增加还出现了38pS长开放通道。在50pS短开放通道的记录中，ACTH^1-24和吗啡可显著抑制创伤大鼠海马CA1区锥体神经元NMDA受体通道的开放概率和开放时间；预中入阿片受体拮抗剂纳络酮能阻断上述的抑制效应。结论 ACTH和吗啡对伤害性信息传递的调制作用可能与其通过阿片受体抑制创伤大鼠海马NMDA受体通道动力学特性的变化有关。     

The effect of coriaria lactone on NMDA receptor mediated currents in rat hippocampal CA1 neurons

Epileptogenesis of (CL) has been verified bymany studies. We can establish an ideal animalmodel of epilepsy on the basis of these studiesll' ZJ.Homeostasis of cytoplasmic free Ca2 is the basisfor neuron to perform its normal functions. Theabnormal elevation of cytoplasmic free Ca2 is thekey step in the triggering of a series of pathologicalchanges"'. Our past findings showed that CLcould elevate LCa' j, of hippocampal neurons[4].But there was no report about the way thoughwhich CL ele…     

N-甲基-N-顺式-苯乙烯基-桂皮酰胺对青霉素 致痫大鼠痫样放电的影响

 【目的】 探讨黄皮核提取物N-甲基-N-顺式-苯乙烯基-桂皮酰胺对青霉素(PNC)诱发大鼠癫痫的影响&#65377;【方法】 32只SD大鼠随机分成正常对照组 (20 mL/L吐温80 + 生理盐水)&#65380;模型对照组 (20 mL/L吐温80 + PNC)&#65380;低剂量桂皮酰胺组(桂皮酰胺75 mg/kg + PNC)&#65380;高剂量桂皮酰胺组(桂皮酰胺150 mg/kg + PNC),每组8只&#65377;建立大鼠皮层定位注射青霉素诱发惊厥模型,观察并分析两剂量的桂皮酰胺腹腔注射前处理给药对造模后大鼠惊厥发作程度和皮层脑电图的影响&#65377;【结果】 两种剂量的N-甲基-N-顺式-苯乙烯基-桂皮酰胺均可减轻大鼠癫痫发作程度,延长痫样放电的潜伏期,减少痫波持续时间,在发作后期减少痫波发放频率,与模型对照组比较,差异明显(P < 0.05或P < 0.01)&#65377;然而,对于棘波最高和最低波幅的影响,桂皮酰胺组与模型对照组比较差异无统计学意义(P > 0.05)&#65377;【结论】 天然产物黄皮核提取物N-甲基-N-顺式-苯乙烯基-桂皮酰胺对大鼠皮层定位注射青霉素诱发的惊厥发作和痫样放电具有明显的抑制作用,该天然产物具有一定的抗惊活性&#65377;     

P38MAPK在PTZ致痫大鼠中的激活及丙戊酸钠的干预作用

目的 探讨脑内氨基丁酸(γ-aminobutyric acid,GABA)转氨酶抑制剂丙戊酸钠(Sodium Valproate,简写为SV)对戊四唑(Pentylentetrazol,PTZ)诱导的大鼠癫痫模型的作用.方法 健康SD大鼠38只,随机分为5组,对照组、癫痫组和SV低中高 3个剂量组(5、10、20 mg/kg).观察大鼠腹腔注射PTZ前后癫痫发作的情况,按Racine分级标准记录,同时记录皮层脑电图(ECoG),观察癫痫样放电的潜伏期及1小时内癫痫样放电活动持续时间.应用Western blot电泳分析海马内CA1区P38MAPK及其上游MKK3,下游c-MYC相关蛋白的表达.结果 对照组给PTZ后均出现癫痫发作,程度均为5级,丙戊酸钠组发作程度明显减轻.ECoG潜伏期延长,痫样放电1小时持续时间缩短.同时,与对照组相比,癫痫组和SV 3个剂量组大鼠CA1区蛋白表达强度升高(P<0.05);与癫痫组相比,SV 3个剂量组大鼠CA1区蛋白表达强度降低(P<0.05).结论 SV对PTZ诱导的癫痫大鼠的发作有明显的对抗作用,对癫痫大鼠海马具有保护作用,其作用与P38MAPK通路相关蛋白的表达相关.