川芎嗪改善癫痫大鼠水迷宫成绩和海马PS幅度

目的：观察川芎嗪对青霉素致痫大鼠学习记忆的影响。方法：造模后,腹腔注射川芎嗪,通过水迷宫实验和在体记录海马CA1区群峰电位（PS）以观测大鼠学习记忆的变化。结果：①癫痫发作使大鼠入水找到终点的时间延长 ②癫痫发作后海马CA1区PS幅度降低 ③注射川芎嗪后癫痫大鼠入水找到终点的时间缩短 ④注射川芎嗪后癫痫大鼠海马CA1区PS幅度升高。结论：川芎嗪可能对青霉素致痫大鼠学习记忆的损伤有改善作用。     

柴胡对癫痫模型电活动的调制

目的 :研究柴胡对癫痫发作的影响。方法 :以家兔和大鼠为实验对象 ,用毛果芸香碱致痫 ,采用脑电图和细胞外玻璃微电极记录技术 ,观察柴胡对癫痫模型大脑皮层放电及海马脑片场电位的影响。结果 :腹腔注射柴胡后可使癫痫发作次数及发作持续时间显著减少 ,发作间隔时间显著延长 ,(P <0 .0 5 ) ,脑片旁滴注柴胡后使致痫大鼠海马脑片诱发场电位幅度平均降低 2 0 .4 1% ,恢复时间平均为 6 .86min ,(P <0 .0 1)。结论 :柴胡注射液能明显抑制癫痫模型电活动 ,提示柴胡具有抗痫作用     

羟基马桑毒素所致的大鼠海马锥体细胞痫样放电活动

本研究采用离体海马脑片电生理研究技术,细胞外记录海马锥体细胞群体锋电位(population spike,PS),观察羟基马桑毒素(tutin)对大鼠海马脑片CA1区锥体细胞电活动的影响,探讨tutin是否具有致痛作用及其致痫机制。结果如下:(1)用40、30和20μg/ml浓度的tutin灌流海马脑片,可显著增高由顺向刺激Schaffer侧支所诱发的PS的幅度,灌流tutin 30min时,PS第一个波的幅度分别为对照的(388.7±20.1)%、(317.2±19.1)%和(180.9±11.6)%(各组n=5,P<0.05)。(2)伴随PS波幅的增高,可出现成串痫样放电波,波数4～11个不等。(3)灌流tutin后的部分脑片(n=9/34),在未刺激Schaffer侧支时也出现自发的成串、高幅痫样放电。(4)灌流CNQX阻断非NMDA受体后,再灌流tutin,PS幅度和放电波数均无显著性变化,即CNQX可完全抑制tutin所致的痫样放电;灌流AP-5阻断NMDA受体后,tutin仍可使PS幅度增高但放电波数无显著性增加,即AP-5可部分抑制tutin所致的痫样放电。上述结果表明,tutin可使海马脑片锥体细胞兴奋活动增强,具有致痫作用;兴奋性谷氨酸受体尤其是非NMDA受体可能介导tutin的致痫作用。     

马桑内酯在Wistar大鼠海马脑片上引起的痫样放电及SC_(1001)钠盐的对

马桑内酯(CoriariaLactone,CL)是从抗精神病中草药—马桑寄生中提取的有效成分,它具有致痫作用。目前,运用CL在整体动物身上建立急、慢性癫痫模型的实验已获成功。为了进一步从细胞水平探讨CL的致痫作用及可能的电生理机制,并观察抗癫新药SC1001钠盐对CL所致痫样放电活动的抑制作用,本实验采用离体海马脑片技术,在59例Wistar大鼠的海马脑片标本上进行了以下研究:以海马CA1区锥体细胞诱发场电位为指标,观察了不同刺激强度时顺向、逆向刺激与诱发场电位之间的关系;观察了持续灌流人工脑脊液(ACSF)对诱发场电位的影响和双脉冲易化,频率…     

血小板激活因子对大鼠海马脑片CA1区LTP的作用

目的:为了探讨血小板激活因子(platelet-activating factor,PAF)对大鼠海马脑片CA1区的长时程增强效应(long-term potentiation,LTP)的影响.方法:应用离体脑片电生理记录技术,记录大鼠海马CA1区的兴奋性突触后电位EPSP,研究了PAF对大鼠海马脑片CA1区的突触传递和可塑性的影响.结果:小剂量(1μmol/L)PAF可诱发大鼠海马CA1区LTP的产生;大剂量(10～50μmol/L)PAF不能诱发大鼠海马CA1区LTP的产生,且不能阻止高频电刺激(HFS,100 Hz,1 000 ms×2,每隔20 s给予)Schffer侧支引起的大鼠海马脑片CA1区LTP的形成和维持.大剂量PAF对海马CA1区基础EPSP没有影响.PAF受体拮抗剂银杏苦内酯(ginkgolide B,GB)可拮抗小剂量PAF诱发大鼠海马CA1区LTP的产生.结论:大剂量PAF具有神经毒性,可能是通过抑制海马CA1区的LTP的形成而参与艾滋病痴呆(HIV-1 associated dementia,HAD)的形成机制.     

一氧化氮的释放对海马脑片CAl区痫样放电的影响

用自制的一氧化氮（NO）敏感电极──Nation-壳聚糖合镍修饰铂电极（Nation-CTS（Ni）-Pt）连续测定了青霉素致痫海马脑片CAl区锥体层神经元NO的释放,并同时观察了NO合酶抑制剂7-nitro-indaole（7-NI）及Nω-nitro-L-arginine（L-NNA）对诱发痫波及NO释放量的影响。研究观察到：（1）在青霉素致痫脑片模型上,诱发的痫波随青霉素浓度的增加而增多,与此同时,NO释放量亦增加并存在剂量反应关系;（2）NO合酶抑制剂7-NI及L-NNA抑制海马脑片CAl区NO的产生的同时,可部分翻转青霉素的致痫作用;（3）NO敏感电极检测线性范围为4．5×10－4～1．0×10－8mol／L,可用于生物组织如脑片的NO释放量测定。结果提示,NO可能有致痫作用;L-NNA及7-NI对癫痫有抑制作用;NO敏感电极的应用为生物体NO的连续实时测定提供了有效的实验工具。     

海马脑片抗癫痫药物研究的离体模型

目的：建立离体海马脑片癫痫样放电模型并用于抗癫痫药物研究。方法：在豚鼠海马脑片上灌流青霉素建立颠阗痫样放电的离体模型。并用此模型对抗癫痫药物苯巴比妥钠和苯妥英钠两种药物在不同浓度下对癫痫样放电的对抗作用进行了定量分析,结果：在海马脑片上灌流致痫药物可建立一个较好的离体组织癫痫样放电模型,苯的对抗作用进行了定量分析,结果：在海马脑片上灌流致痫药物可建立一个较好的离体组织癫痫样放电模型。苯巴比妥和苯妥英钠在一定浓度下均有显著对抗癫痫样放电的作用,且与整体实验的结果相一致。结论：本实验建立有离体脑片模型具有实验手段简单,方法灵活,易于建立药物量效关系等优点,可用于抗癫痫药物筛选和研究。     

氟桂利嗪对青霉素致痫大鼠皮层及海马癫痫样放电的影响

目的:观察氟桂利嗪对青霉素致痫大鼠皮层和海马癫痫样放电的影响.方法:选取Wistar大鼠60只制作青霉素致痫模型,在大鼠海马、颞叶、额叶皮层埋置电极,记录氟桂利嗪(20 mg/kg)灌胃后大鼠癫痫样放电的变化.结果:实验组动物皮层及海马癫痫样放电潜伏期明显延长,持续时间缩短,单位时间内癫痫样放电数明显减少,与对照组相比有显著差异.结论:氟桂利嗪具有明显抗癫痫作用,可显著抑制青霉素致痫鼠皮层及海马区癫痫样放电.     

液压打击损伤后海马CA1区神经元兴奋性变化的研究

为考察脑损伤对海马CA1区锥体神经元电活动的影响并研究大黄素对神经元的超兴奋性和突触传递的作用,应用液压打击大鼠脑损伤模型和细胞外记录方法提取诱发的海马CA1区场兴奋性突触后电位(fPSP)和群峰电位(PS),进行相关的数据处理和分析。发现损伤侧比非损伤侧的fPSP斜率明显升高,PS波峰个教显著增加,而PS潜伏期明显减小;在灌流液中施加大黄素,CA1区诱发场电位明显减弱。研究结果表明：颅脑损伤可造成海马CA1区锥体神经元的迟发性过度兴奋;大黄素对神经元的兴奋性有抑制作用,可能对颅脑损伤后的中枢神经系统具有保护功能。     

戊四氮致痫大鼠皮质和海马内GFAP、cyclinD1及脑和脑脊液17β-雌二醇和孕酮浓度变化

目的研究癫痫发作后脑和脑脊液中17β-雌二醇和孕酮含量的变化.方法将雌性SD大鼠随机分为戊四氮(PTZ)致痫组和生理盐水对照组.(1)用免疫组织化学方法观察大鼠大脑皮质和海马星形胶质细胞胶质原纤维酸性蛋白(GFAP)含量的变化;(2)用Western blot方法检测大鼠大脑皮质和海马细胞周期素D1(cyclin D1)表达的变化;(3)采用放免法测定大鼠大脑皮质和海马组织匀浆及脑脊液中17β-雌二醇和孕酮含量的变化.结果免疫组织化学染色结果显示癫痫发作4h后在海马CA3区、CA1区和皮质内GFAP免疫反应明显增强(P<0.05);Western blot结果显示癫痫发作2h后cyclin D1的表达在皮质和海马均较对照组明显增强(P<0.05);放射免疫分析结果显示,癫痫发作后,皮质、海马和脑脊液的17β-雌二醇的浓度有不同程度增高,致痫8h后恢复正常,孕酮的浓度在皮质和脑脊液则呈下降趋势.结论戊四氮致痫时皮质及海马内星形胶质细胞激活、增殖,内源性雌激素合成增多,同时孕酮浓度降低,说明雌性激素在癫痫的形成和维持中发挥作用.     

Effects of Chronic Stress and Phenytoin on the Long-term Potentiation （LTP） in Rat Hippocampal CA1 Region

Stress is the response to stimulation from inside andoutside with complicated effects on organisms. Appropri-ate stressful reactions are helpful in resisting diseases byactivating unspecific modulation system, while severe orprolonged stresses are harmful and even induce mentaland physical disorders such as recurrent depression, post-traumatic stress disorder (PTSD), Alzheimer’s disease andepilepsy [1]. Hippocampus, a main brain region of keyimportance for learning, memory and emotion, is t…     

Rosiglitazone Suppresses In Vitro Seizures in Hippocampal Slice by Inhibiting Presynaptic Glutamate Release in a Model of Temporal Lobe Epilepsy

Peroxisomal proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor whose agonist, rosiglitazone has a neuroprotective effect to hippocampal neurons in pilocarpine-induced seizures. Hippocampal slice preparations treated in Mg²⁺ free medium can induce ictal and interictal-like epileptiform discharges, which is regarded as an in vitro model of N-methyl-D-aspartate (NMDA) receptor-mediated temporal lobe epilepsy (TLE). We applied rosiglitazone in hippocampal slices treated in Mg²⁺ free medium. The effects of rosiglitazone on hippocampal CA1-Schaffer collateral synaptic transmission were tested. We also examined the neuroprotective effect of rosiglitazone toward NMDA excitotoxicity on cultured hippocampal slices. Application of 10μM rosiglitazone significantly suppressed amplitude and frequency of epileptiform discharges in CA1 neurons. Pretreatment with the PPARγ antagonist GW9662 did not block the effect of rosiglitazone on suppressing discharge frequency, but reverse the effect on suppressing discharge amplitude. Application of rosiglitazone suppressed synaptic transmission in the CA1-Schaffer collateral pathway. By miniature excitatory-potential synaptic current (mEPSC) analysis, rosiglitazone significantly suppressed presynaptic neurotransmitter release. This phenomenon can be reversed by pretreating PPARγ antagonist GW9662. Also, rosiglitazone protected cultured hippocampal slices from NMDA-induced excitotoxicity. The protective effect of 10μM rosiglitazone was partially antagonized by concomitant high dose GW9662 treatment, indicating that this effect is partially mediated by PPARγ receptors. In conclusion, rosiglitazone suppressed NMDA receptor-mediated epileptiform discharges by inhibition of presynaptic neurotransmitter release. Rosiglitazone protected hippocampal slice from NMDA excitotoxicity partially by PPARγ activation. We suggest that rosiglitazone could be a potential agent to treat patients with TLE.     

Eugenol depresses synaptic transmission but does not prevent the induction of long-term potentiation in the CA1 region of rat hippocampal slices

Using field potential recording in the CA1 region of the rat hippocampal slices, the effects of eugenol on synaptic transmission and long-term potentiation (LTP) were investigated. Population spikes (PS) were recorded in the stratum pyramidal following stimulation of stratum fibers. To induce LTP, eight episodes of theta pattern primed-bursts (PBs) were delivered. Eugenol decreased the amplitude of PS in a concentration-dependent manner. The effect was fast and completely reversible. Eugenol had no effect on PBs-induced LTP of PS. It is concluded that while eugenol depresses synaptic transmission it does not affect the ability of CA1 synapses for tetanus-induced LTP and plasticity.     

Effects of gamma-aminobutyric acid antagonist, 4-ethyl bicyclo-phosphate, on total and synaptic evoked responses in neurons of hippocampal slices

Influence of 4-E-BPE on the amplitude of population spices (PS) evoked in CA1 area by Shaffer collateral stimulation in hippocampal slices were analysed. Bath application of 4-E-BPE (10(-6)-10(-5) M) led to a pronounced increase in the amplitude of the PS, the appearance of secondary PS and then introduction of GABA led to restoring original state. The 4-E-BPE was more potent than picrotoxin. These findings suggest that 4-E-BPE suppress inhibitory synaptic transmission in the CA1 region of hippocampus.     

Effects of adenosinergic drugs on hypoxia-induced electrophysiological changes in rat hippocampal slices.

The effects of adenosinergic antagonists caffeine and DPCPX, and of the adenosinergic agonists L-PIA, CPA and CGS 21680 were investigated on fully and partially reversible hypoxia-induced electrophysiological changes in rat hippocampal slices. The influence of a high potassium solution and of the N-methyl-D-aspartate antagonist dizocilpine (MK 801) was also tested. The latency to obtain a 50% decrease in the amplitude of the CA1 population spike (CA1 PS) during a short- (5-10 min) lasting hypoxic period was significantly increased (P less than 0.01) by slice perfusion with caffeine (50 microM), DPCPX (0.2 microM), and by increasing (from 3 to 4 mM) the potassium concentration in the medium bathing the hippocampal slices. The latency was significantly decreased (P less than 0.01) by slice perfusion with L-PIA (0.2 microM) and CPA (0.05 microM). It was not significantly modified by CGS 21680 (5 microM). The incidence of reappearance of the CA1 PS during reoxygenation after long- (45 min) lasting hypoxia was significantly increased (P less than 0.05) by slice perfusion with MK 801 (50 microM), while it was not significantly affected by slice perfusion with caffeine (50 microM) or DPCPX (0.2 microM) or L-PIA (0.2 microM) or CPA (0.05 microM) or CGS 21680 (5 microM). The results indicate a prevalent involvement of the A1 adenosine receptors in the early mechanisms underlying hypoxia-induced reversible changes. Adenosine seems to have a limited role in the late mechanisms occurring after a long-lasting hypoxic period.     

In vitro functional differentiation of hippocampal corticosterone receptors by mineralo- and glucocorticoids

Modulation of CA1 evoked electrophysiological properties (amplitude, latency, paired-pulse facilitation) by different concentrations of aldosterone (ALDO), spironolactone (SPI), and corticosterone (CT) was studied in hippocampal slice preparation from BALB/c mice. ALDO (5 nM) induced a prolonged increase of the population spike (PS) amplitude with a decrease of its latency and of the paired pulse facilitation. The same effect was observed with a solution of CT (0.5 nM) alone or combined with ALDO (0.5 nM), but no effect was observed with a solution of combined CT (0.5 nM) and SPI (500 nM). Implication of corticosteroid receptors in this response was discussed.     

Diurnal actions of melatonin on epileptic activity in hippocampal slices of rats

Since melatonin receptors have been found in the hippocampus of mammals it has been suggested that melatonin can modulate neuronal functions of hippocampal cells. The effect of melatonin (10 nM/l and 1 microM/l) on frequency and amplitude of epileptiform field potentials (EFP) elicited by low Mg(2+) or by bicuculline was tested in the CA1 region of hippocampal slices of rats. In the low Mg(2+) model, melatonin, applied in a near physiological concentration of 10 nM/l, exerts no effect on EFP in slices prepared at night or during the day. In a concentration of 1 microM/l, however, melatonin enhances the frequency of EFP to approximately 140% in slices prepared during the day. This effect was suppressed through simultaneous administration of the melatonin receptor antagonist luzindole (10 microM/l). In contrast, melatonin did not affect epileptic activity in slices prepared at night. Epileptiform discharges elicited by blocking the GABAergic inhibition (bicuculline model) were not affected by melatonin, either during the day or at night. The results indicate that melatonin affects epileptic activity in a diurnal manner and that the action of melatonin is different in relation to the epilepsy model.     

GABA对大鼠海马脑片缺氧损伤的保护作用

目的：研究GABA对大鼠海马脑片急性缺氧损伤的保护机制。方法：采用成年大鼠离体海马脑片,用胞外记录的电生理技术,观察GABA对急性缺氧后海马脑片诱发电位的影响。结果：（1）GABA可明显延迟PV的消失,但对PS却无影响;（2）给予GABAA受体拮抗剂荷包牡丹碱（bicuculine)以及Cl^-通道阻抗剂NPPB可阻断GABA的保护作用。结论：GAB可提高海马脑片耐缺氧能力,其机制可能与GABA通过GABAA受体提高Cl^-内流有关。