海人酸致痫大鼠海马细胞外氨基酸类神经递质的变化

目的 分析海马细胞外氨基酸递质在癫痫发生中的作用,探讨海人酸致痫模型大鼠癫痫发生的机制.方法 应用立体定向方法建立海人酸大鼠颞叶癫痫模型,观察大鼠行为学和电生理变化,应用电镜观察大鼠海马超微结构,应用微透析获取大鼠海马细胞外液,高压液相色谱法测定透析液中的兴奋性氨基酸谷氨酸、抑制性氨基酸牛磺酸及γ-氨基丁酸的含量.结果 海人酸注射后大鼠出现典型的颞叶癫痫发作,皮层脑电显示痫性发作,电镜显示兴奋性神经递质增加,高效液相色谱分析显示海马细胞外谷氨酸、牛磺酸和γ-氨基丁酸含量明显高于对照组(P＜0.05),虽然谷氨酸、γ-氨基丁酸都升高,而谷氨酸升高的更明显.结论 兴奋性氨基酸与抑制性氨基酸的失衡在海人酸致痫大鼠模型的癫痫发生过程中发挥重要作用,是癫痫发生的原因之一.     

炎性细胞因子在癫痫发生发展中的作用

越来越多的证据证实了神经炎症在癫痫发展中的基本作用,炎性细胞因子是大脑炎症反应的关键因素。研究表明,癫痫发作与炎性细胞因子水平升高有关,尤其是白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)和转化生长因子-β(Transforming growth factor-β,TGF-β),这强调了神经炎症和炎性细胞因子对过度兴奋大脑的影响和在癫痫发生中的作用。由于癫痫的病理生理学尚不清楚,因此确定炎性细胞因子在癫痫发生中的可能作用有助于解开癫痫的病理生理学。了解炎性细胞因子在癫痫中的作用可以为我们治疗癫痫特别是耐药型癫痫提供有希望的靶点。本综述概述了神经炎症及其主要介质的作用,包括IL-1β、IL-6、TNF-α和TGF-β相关性癫痫的病理生理学。此外,还讨论了炎性细胞因子和细胞因子受体在癫痫治疗中的潜在靶向性。     

甲基强的松龙对多发性硬化血清细胞因子的影响

目的:观察甲基强的松龙(methylprednisolone,MP)对活动期多发性硬化(active multiple sclerosis,AMS)血清细胞因子网络的影响。方法:AMS台疗前、静滴(1g·d~(-1))3 d后即刻、24、96 h留取静脉血。检测白细胞介素-1β(interleukin-1β、IL-1β)、IL-2、IL-4和肿瘤坏死因子-a(tumor necorsis factor-a,TNF-a)、IL-10和干扰素γ(interferon-γ,IFN-γ)。结果:治疗前,AMS血清IL-1β、IL-2及IL-10较正常组显著升高(P<0.005,P=0.001,P=0.012),IL-4浓度和正常对照组相似。治疗后,血清IL-1β、IL-2、浓度比治疗前显著降低(P均<0.001),并有逐渐减低的趋势,IL-10浓度逐渐升高,但无统计学意义(P>0.05),IL-4比治疗前显著升高(P<0.05)。结论:MP可能通过调节AMS细胞因子网络中前炎性(TH1)和抗炎性(TH2)细胞因子来抑制TH1细胞的免疫应答。     

实验性大鼠脑出血灶周围区内细胞因子IL-1β的表达

目的研究脑出血区白细胞介素-1 β(IL-1 β)表达的动态变化,探讨脑出血的病理生理过程,为临床治疗脑出血提供理论依据.方法纹状体内注入胶原酶造模,采用免疫组织化学亲合素-生物素-过氧化物酶复合物法(ABC)观察细胞因子IL-1 β在脑出血后4、14、24、72 h和7 d的表达变化.结果大鼠脑出血后4 h病变局部即有明显的IL-1 β表达,阳性细胞呈胶质细胞形态;至脑出血后14 h,IL-1 β阳性的细胞数量比4 h组明显增多(P<0.05),染色更深,细胞形态相似;至24 h,IL-1 β蛋白的表达达到顶峰(P<0.05),阳性细胞密集,染色最深,形态仍然同前.24 h以后,IL-1 β蛋白的表达则逐渐下降,至脑出血72 h后局部几乎无IL-1 β阳性的细胞(P<0.05);一直至脑出血7 d时,局部仍未见到IL-1 β阳性的细胞.所有动物非出血侧纹状体均未见到明显的IL-1 β阳性细胞.结论 IL-1 β在脑出血区表达增高,脑出血后病变局部可能存在着与病程相关的炎性反应,在一定时间内采取有效的对抗炎性细胞因子的治疗可能对脑出血患者的预后有一定的意义.     

癫痫大鼠脑内白细胞介素6的表达特征

有临床资料显示，有癫痫病史或癫痫发作的患者脑脊液和血浆白细胞介素6(IL-6)浓度升高，动物实验也证明，在各种癫痫发作模型中脑内IL-6表达增加。我们试图通过研究红藻氨酸(KA)诱导癫痫发作的动物模型相关脑区中IL-6的表达特征及其与c—Fos表达的比较，进一步探讨IL-6在癫痫发作中的意义及其细胞学来源。     

阿尔茨海默病患者脑脊液细胞因子研究

目的:探讨细胞因子在阿尔茨海默病(AD)发病机制中的意义和临床诊断价值。方法:采用双抗体夹心酶联免疫吸附试验分别对25例患者脑脊液(CSF)白细胞介素1β(IL-1β)、白细胞介素6(IL-6)及肿瘤坏死因子α(TNF-α)水平检测。结果;AD患者CSFIL-1β、IL-6和TNF-α含量均较正常老年人显著为高(P均<0.01)。结论;AD患者CSFIL-1β、IL-6和TNF-α含量较正常老年人显著增高,为AD的慢性免疫炎症机制提供了理论依据。     

侧脑室注射IL-1β、IL-1ra对癫痫大鼠脑皮层、海马Fos蛋白表达的影响

目的　了解外源性和内源性白细胞介素 - 1(IL- 1)对戊四氮 (PTZ)致痫大鼠脑皮层、海马神经元兴奋性的影响。方法　应用流式细胞免疫荧光技术对大鼠大脑皮层、海马 Fos表达进行定量分析。结果　 IL- 1β和IL - 1ra侧脑室注射后再致痫大鼠分别较单纯 PTZ致痫大鼠皮层海马 Fos表达显著增高和下降 (P<0 .0 1,P<0 .0 5)。结论　内源性和外源性 IL- 1β均有增高癫痫大鼠脑皮层及海马神经元兴奋性的作用。     

抑郁症患者血清白细胞介素-1β,6的水平及其发病机制的对照研究

目的　探讨抑郁症的细胞免疫改变及其可能的发病机制。方法　采用酶联免疫吸附法 ,对 31例抑郁症患者在抗抑郁治疗前后分别进行HAMD评定及IL - 1β ,IL - 6的检测 ,并以 2 1例健康者作对照。 结果　抑郁症治疗前IL - 1β及IL - 6水平显著高于正常对照组 (P <0 0 5 ) ,且经 4～ 10周左右治疗后 ,二者明显下降。但疗前HAMD评分高低与疗前IL - 1β及IL - 6水平并无相关性 (P >0 0 5 )。 结论　免疫系统激活及炎症反应确实参与抑郁症的发病过程 ,但本研究尚不能确定抑郁症严重度 (HAMD评分 )与血清IL - 1β及IL - 6水平存在相关性。     

姜黄素对脑出血大鼠血肿周边炎性细胞因子水平的影响

目的:探讨脑出血(ICH)后血肿周边炎性细胞因子水平变化以及姜黄素对其影响。方法:120只SD大鼠随机分为假手术组(n=40);脑出血组(ICH对照组,n=40)和姜黄素治疗组(Cur治疗组,n=40)。每组分为手术前、术后6h、12h、24h、48h、72h、96h、120h等8个时点,每个时点5只大鼠。采用立体定向自体血注入大鼠尾状核建立ICH模型,观察各组术前及术后各时点血肿周边脑组织白细胞介素-2(IL-2)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平。结果:ICH对照组术后24～120h各时点IL-2,IL-6水平及12～96h各时点TNF-α水平均明显高于假手术组(P<0.05)。Cur治疗组术后24～120h各时点IL-2,IL-6水平及12～96h各时点TNF-α水平均明显低于ICH对照组(P<0.05)。结论:脑出血后血肿周边炎性细胞因子水平升高可能加重血肿周边脑损伤,Cur干预后使炎性细胞因子水平降低,从而可能减轻血肿周边脑损伤。     

TNF-α对PTZ点燃大鼠海马Glu能神经元和GABA能神经元的影响

目的:探讨肿瘤坏死因子-α在癫痫中的作用机制。方法:应用免疫组织化学的方法研究TNF-α对戊四氮致癫痫大鼠海马Glu能神经元和GABA能神经元的影响。结果:大鼠海马谷氨酸能神经元的改变;戊四氮致癫痫组明显高于正常对照组,TNF-α干扰组明显高于戊四氮致癫痫组和正常对照组。大鼠海马GABA能神经元的改变;戊四氮致癫痫组明显低于正常对照组,TNF-α干扰组明显低于戊四氮致癫痫组和正常对照组。结论:TNF-α可以通过增强海马谷氨酸能神经元的活性和降低GABA能神经元的活性而促进癫痫的发生和发展。     

Prenatal haloperidol exposure: Effects on brain weights and caudate neurotransmitter levels in rats

Monoamines may exert a trophic effect on early brain development. To assess the role of dopamine in prenatal neurological development of the rat, haloperidol (HAL) was given in daily 2.5 or 5 mg/kg SC doses to dams over gestational days 6 to 20. This treatment regime did not enhance fetal mortality, but did produce reliable, if modest, stunting of the body and brain weight of offspring. The 5 mg/kg HAL dose consistently reduced offspring brain weight to roughly 90% of controls. This effect was probably permanent, in that it was seen throughout maturation and in adults as late as 140 days of postnatal age. Appropriate controls showed that this effect was not due to drug-induced reductions in food intake, to the presence of HAL in maternal milk, or to behavioral abnormalities in HAL-exposed dams. These effects had, at best, modest regional specificity, in that most brain regions were affected, independently of degree of dopaminergic innervation. Closer investigation of HAL effects on the striatum suggested that this permanent weight reduction was not accompanied by alterations in striatal concentrations of monoamines, monoamine metabolites, amino acids, choline, acetylcholine, DNA, protein, or water. It is concluded that prenatal HAL does stunt growth, but that this effect may not involve a direct drug influence restricted to the fetal dopamine system in the brain.     

Nicotine-induced monoamine neurotransmitter changes in the brain of young rats

A number of studies in various species including man indicated a greater risk of drug preference and addictive behavior in young as compared to adults. Such age dependent preference was also found with nicotine. To examine possible mechanisms for this difference in our continuing study of reward mechanisms, we compared nicotine-induced neurotransmitter changes in the brain regions of adult and young Sprague-Dawley rats, assaying the transmitters via microdialysis in conscious freely moving animals. In general, nicotine-induced changes were significantly less in the regions measured in the young. Nicotine-induced effects on dopamine in the dorsal and ventral hippocampus (VH), prefrontal and medial temporal cortex, and superior cerebral peduncle were lower in the young than in adult, the same in the ventral tegmental area (VTA) and lateral septal nucleus (LS), and somewhat higher in the nucleus accumbens shell (NAccS). Norepinephrine levels in the young were lower in all areas except in the VH where they were the same, and serotonin levels were lower except in the VTA and LS where they remained the same, and higher in the NAccS. Age-dependent differences in the metabolites measured were more mixed. We conclude that the greater nicotine preference in young is not paralleled by a greater effect of nicotine on the release of monoamines at least in most of the brain areas assayed. Thus, increases of nicotine reward are not likely due to increases of monoamines in reward and cognitive areas. The small increase of dopamine (DA) and more significant increase of serotonin (5-HT) only in the NAccS are of significance, and would indicate a more significant role of 5-HT than of DA at least in the age difference in nicotine preference. Developmental changes in receptor composition and distribution involving several transmitter systems and other components such as neuropeptides are also likely to play a role.     

大鼠脑缺血再灌注后全脑及血清炎性因子水平研究

脑组织间未见显著性差异;血清中两者升高均晚于脑组织,且升高幅度较低.缺血灶的大小与上述炎症因子的水平相一致.结论 炎性反应遍及全脑并作用于全身,贯穿于脑缺血冉灌注损伤的整个病理过程.     

Sleep deprivation: Effects on circadian rhythms of rat brain neurotransmitter receptors

Specific binding of ligands to rat forebrain α- and β-adrenergic, muscarinic cholinergic, opiate, benzodiazepine, and striatal dopamine receptors was measured at 4-hour intervals during the last 13 hours of a 24-hour sleep deprivation period, and during the first 11 hours of the recovery sleep period. In non-sleep-deprived controls a 24-hour rhythm in binding was evident. The minor differences between the sleep deprivation group and the control group consisted mainly in a reduced amplitude of the 24-hour rhythm under the sleep deprivation schedule. The results indicate that neither the 24-hour forced locomotion nor the subsequent prominent sleep rebound is accompanied by marked changes in the number of neurotransmitter receptors and their circadian rhythms.     

可卡因成瘾大鼠脑立体定向核团毁损术前后形态学及单胺类神经递质的变化

目的研究可卡因成瘾大鼠脑形态学的变化及在脑立体定向核团毁损术前后单胺类神经递质的变化。方法采用普通SD大鼠作为实验动物,随机分为对照组、成瘾组、成瘾大鼠毁损伏核组、成瘾大鼠毁损海马组、成瘾大鼠毁损扣带回组、成瘾大鼠毁损伏核-海马-扣带回组。成瘾大鼠每天皮下注射溶解于0.2ml蒸馏水的盐酸可卡因15mg/kg,正常对照组每天皮下注射0.2ml蒸馏水,持续90 d。毁损组分别行不同部位的毁损,3 d后处死,采用高效液相色谱仪(HPLC)脑组织匀浆法检测纹状体的单胺类递质含量,同时观察比较正常、成瘾及毁损后大鼠不同脑区在光镜及电镜下形态学的改变。结果成瘾大鼠纹状体多巴胺含量较正常对照组升高(P<0.01)。毁损前后大鼠单胺类递质无明显变化。在成瘾大鼠的伏核、海马、扣带回观察到核固缩、间质水肿、纤维断裂及坏死。结论长期使用可卡因可以造成大鼠脑组织的损害及纹状体多巴胺含量升高。立体定向核团毁损术前后脑组织单胺类神经递质变化不明显。     

Neurochemical changes of long-term adrenalectomy in rat brain: Effects on neurotransmitter amino acids

The levels of five amino acids together with glutamine synthetase activity, were measured in brain regions of rats with bilateral adrenalectomy, performed in newly weaning rats on postnatal day 22 and sacrificed 3 months later. Adrenalectomy caused a general decrease of glutamine concentration in three hippocampal regions (CA1-CA2, CA3, CA4-dentate gyrus), in hypothalamus, striatum and cerebellum. This reduction, which was particularly significant in hippocampus and cerebellum, was paralleled by a decrease of glutamine synthetase activity. Treatment with corticosterone reversed the effect of adrenalectomy. Little or no change was observed in the tissue levels of taurine, aspartic, glutamic or gamma-amino butyric acids.     

Effects of chronic D-amphetamine and phenylethylamine on the concentrations of neurotransmitter amino acids in the rat brain

Rats were treated acutely and chronically with D-amphetamine or phenylethylamine. Following the treatments, the concentrations of amino acids in the hypothalamus and caudate nucleus were measured from prederivatized tissue extracts using reversed phase high pressure liquid chromatography with fluorescence detection. Acute amphetamine slightly decreased the caudate glutamine concentration, and chronic treatment for 10 days increased caudate aspartate content. Chronic phenylethylamine enhanced the taurine content, both in caudate and hypothalamus. No significant changes were observed in the concentrations of glutamate, GABA or alanine. The results indicate that these two stimulants can modify the brain metabolism of certain neuroactive amino acids in addition to the metabolism of catecholamines. The specific effect of chronic phenylethylamine on taurine concentration suggests an adaptive response of taurine-containing cells to repeated administrations of phenylethylamine.     

Effects of early lead exposure on neurotransmitter systems in the brain. A review with commentary

The mechanism by which early lead exposure alters the functional development of the brain remains an open question. One primary avenue of approach has been to study the effects of neonatal lead exposure on neurotransmitter systems. This paper reviews the published data related to the interaction of lead with each of those systems. Further, each dosing paradigm has been evaluated with a view to experimental error and interactive variables. It was concluded that factors such as the time at which pregnant animals were shipped and mode of dosing may have been uncontrolled variables causing variability in reported results between and within laboratories. The majority of publications deal with the interaction of lead with catecholamine systems and with dopamine in particular. Reports of effects are highly variable and many observations lack confirmation by other laboratories or have not been replicated. However, the bulk of observations leads to the tentative conclusion that lead does result in an altered functional state of the catecholamine systems. This is true for cholinergic function as well. Some perturbation of acetylcholine metabolism probably exists but the specificity and significance of the effect are suspect. Reports that lead alters the functional state of GABA pathways are interesting but require confirmation. The generality and variability of effects on neurotransmitter systems questions the degree of specificity that may be expected. It is suggested that lead may effect a variable change in the functional state of all these systems by limiting glucose metabolism during periods of vulnerability.