应激对大鼠海马谷氨酸、天冬氨酸和γ-氨基丁酸含量的影响

目的　探讨应激对大鼠海马谷氨酸、天冬氨酸和γ 氨基丁酸 (GABA)含量的动态影响。方法　将 72只健康雄性大鼠随机分为 5个应激暴露不同时间组和对照组 ,每组 12只。利用高效液相色谱仪 紫外检测法 ,分别于应激第 1,3,7,14和 2 8天观察应激对大鼠海马谷氨酸、天冬氨酸及GABA含量的影响。结果　应激第 1天组大鼠海马谷氨酸和天冬氨酸含量与对照组相比 ,差异无显著性 ;但GABA含量 [(2 74 7± 0 339) μmol/g]低于对照组 [(3 719± 0 5 2 8) μmol/g;P <0 0 5 ]。应激第 3,7,14和 2 8天组谷氨酸含量 [分别为 (7 818± 0 799) μmol/g ,(9 0 0 7± 0 5 2 0 ) μmol/g,(8 0 4 9± 0 733) μmol/g和 (8 12 9± 1 5 5 6 ) μmol/g]高于对照组 [(6 4 11± 0 6 38) μmol/g];天冬氨酸含量 [分别为 (2 717± 0 2 5 8)μmol/g,(2 6 96± 0 317) μmol/g,(2 82 8± 0 4 6 8) μmol/g和 (4 6 4 9± 0 6 37) μmol/g]也高于对照组 [(2 0 0 3± 0 2 71) μmol/g];均P <0 0 1。应激第 14天组和 2 8天组GABA含量 [分别为 (4 4 6 2± 0 883) μmol/g和(4 4 97± 0 85 7) μmol/g]高于对照组 (P <0 0 5～0 .0 0 1) ,应激第 3天组和 7天组的GABA含量与对照组间的差异无显著性。结论　应激第 3天开始     

捕食应激致大鼠海马钙/钙调素依赖性蛋白激酶途径调控紊乱

目的　探讨创伤后应激障碍 (PTSD)样行为异常的神经生物学机制。方法　将 16 0只Wistar大鼠随机分为捕食应激组和对照组 (每组各 80只 )。采用流式细胞仪、荧光标记术和免疫印迹法 ,检测捕食应激后 4 8h内大鼠海马细胞内游离Ca2 + 浓度与钙调素 (CaM )相对活性平均通道荧光 ,以及海马组织总CaM、Ca2 + /CaM依赖性蛋白激酶IIα (CaMKⅡα)与IV(CaMKⅣ )的表达变化。结果实验后即刻捕食应激大鼠海马细胞内游离Ca2 + 浓度明显增高 [应激组 (2 81± 70 )nmol/L ,对照组(2 0 7± 5 1)nmol/L ,P <0 0 1],12h增至顶峰 [应激组 (332± 84 )nmol/L ,对照组 (2 2 0± 5 4 )nmol/L ,P <0 0 1],2 4h仍明显增高 [应激组 (2 73± 6 7)nmol/L ,对照组 (2 0 0± 4 8)nmol/L ,P <0 0 1];实验后即刻游离CaM平均通道荧光则同步降低 (应激组 2 2± 0 5 ,对照组 3 4± 0 8,P <0 0 1;2 4h应激组2 7± 0 7,对照组 3 3± 0 8,P <0 0 5 ) ;而海马总CaM于实验后第 2 4h、CaMKⅡα和CaMKⅣ于实验后第 12h内表达明显增高 (P <0 0 1)。结论　捕食应激后早期海马细胞Ca2 + CaM及其依赖性蛋白激酶途径调控紊乱 ,在严重心理应激所致实验大鼠PTSD样行为异常中可能有意义。     

慢性应激致大鼠海马长时程增强和氨基酸类神经递质改变及苯妥英钠的效应

目的　探讨慢性应激对大鼠海马长时程增强 (LTP)和氨基酸类神经递质的影响 ,以及苯妥英钠对LTP和氨基酸神经递质改变的效应。方法　将 2 4只SD雄性大鼠随机分为对照组、应激 生理盐水 (10ml/kg)组和应激 苯妥英钠 (40mg/kg)组 ,每组 8只。采用离体海马脑片结合电生理的方法观测海马CA1区LTP的变化。以群体峰电位 (PS)的幅值和场兴奋性突触后电位 (fEPSP)的斜率作为观察LTP变化的指标。应用高效液相色谱 紫外检测法检测海马氨基酸类神经递质的含量。结果　 (1)应激 生理盐水组PS幅值和fEPSP斜率在高频串刺激后增大的幅度低于对照组和应激 苯妥英钠组 (P <0 0 5 )。 (2 )应激 生理盐水组和应激 苯妥英钠组的天冬氨酸含量 [分别为(4 74 6± 0 6 0 9) μmol/g和 (4 94 8± 0 75 1) μmol/g]高于对照组 [(2 4 2 5± 0 2 11) μmol/g ,P <0 0 1];应激 生理盐水组的谷氨酸含量 [(8 0 94± 1 0 35 ) μmol/g]高于对照组 [(6 0 16± 0 6 77) μmol/g]和应激 苯妥英钠组 [(6 970± 0 6 4 7) μmol/g];P <0 0 5 ;应激 苯妥英钠组的γ 氨基丁酸 (GABA)含量[(5 14 2± 0 6 6 2 ) μmol/g]高于对照组 [(4 2 2 9± 0 4 4 9) μmol/g]和应激 生理盐水组 [(4 2 4 9± 0 4 6 3)μmol/g],P <0 0     

慢性应激对大鼠海马CA3区锥体细胞顶树突及血清皮质酮浓度的影响

目的探讨慢性应激对大鼠海马CA3区锥体细胞结构和血清皮质酮浓度的影响。方法将20只雄性Sprague-Dawley大鼠按体质量随机分为应激组和对照组,每组10只。采用高尔基染色法及酶联免疫分析方法,观察慢性强迫游泳应激对大鼠海马CA3区锥体细胞顶树突和血清皮质酮浓度的影响。结果应激组大鼠海马CA3区锥体细胞顶树突的总长度[(112±10)μm]短于对照组[(168±34)μm],差异有统计学意义(P<0.01);一级树突直径[(9.0±1.1)μm]大于对照组[(5.7±0.9)μm],差异有统计学意义(P<0.01);血清皮质酮浓度[(13±14)μg/L]低于对照组[(30±16)μg/L],差异有统计学意义(P<0.05)。结论慢性强迫游泳可引起大鼠海马CA3区锥体细胞顶树突及血清皮质酮浓度的改变。     

慢性冷水游泳应激对大鼠海马、前脑皮层神经颗粒素含量的影响

目的探讨慢性应激对大鼠海马和前脑皮层神经颗粒素(NG)含量的影响。方法将雄性SD大鼠随机分为应激组(予10℃冷水游泳应激,共2周)、装置对照组和正常对照组,每组10只。于应激前后测量三组大鼠的体质量变化情况,并记录每天应激过程中应激组和装置对照组的排便量以考察应激的强度,应激后以Westernblotting方法测定海马和前脑皮层中的NG含量(以NG含量与βActin含量的比值表示)。结果(1)应激前后,三组大鼠的体质量比较,差异均无统计学意义(P>0.05),但应激组的体质量增长相对缓慢;(2)应激第4—14天应激组的排便量多于装置对照组(P<0.01);(3)应激组和装置对照组海马的NG含量[分别为(0.66±0.13)和(0.94±0.26)]低于正常对照组[(1.93±0.53)],差异有统计学意义(P<0.01);(4)应激组前脑皮层的NG含量[(0.45±0.00)]低于装置对照组和正常对照组[分别为(2.76±1.74)和(2.87±1.63)],差异有统计学意义(P<0.01);(5)应激组海马NG含量高于前脑皮层(P<0.01);装置对照组海马NG含量低于前脑皮层(P<0.01);正常对照组海马与前脑皮层NG含量的差异无统计学意义。结论慢性应激导致海马和前脑皮层NG含量显著下降;对于时程长、程度严重、适应不良的冷水游泳应激,前脑皮层受损比海马更为严重;而对于时程长、程度微弱的装置应激,海马则比前脑皮层更为敏感。     

慢性强迫游泳应激对大鼠情绪和脑细胞外信号调节激酶磷酸化水平的影响

目的探讨慢性强迫游泳应激对大鼠情绪和脑细胞外信号调节激酶磷酸化(P-ERK1/2)水平的影响。方法将30只SD雄性大鼠随机分为游泳应激组、装置对照组和空白对照组,每组10只。游泳应激组每天接受5min的游泳应激,装置对照组每天接受5min的新异场景应激,均连续14 d,空白对照组不进行任何干预,然后观察大鼠行为(体质量增长量、旷场测验和糖精水溶液偏好测验)。采用免疫印迹法测定大鼠海马和前额叶皮质的P-ERK1/2。结果(1)游泳应激组在应激7d和应激14d的体质量增长[分别为(75±22)g和(70±24)g]均低于空白对照组[分别为(101±35)g和(115+47)g],均P＜0.05。(2)装置对照组的粪便排泄量[(1.4±1.9)粒]多于空白对照组[(0.4±1.0)粒]和游泳应激组[(0.1±0.3)粒],均P＜0.05；而游泳应激组的水平活动距离[(2077±1245)cm]少于空白对照组[(2990±1038)cm]和装置对照组[(3110±1462)cm],均P＜0.05。(3)游泳应激组的糖精水溶液摄入量[(11±6)g]和糖精水溶液摄入量占总液体摄入量的比例[(37±16)％]均低于空白对照组[分别为(15±4)g和(47±15)％],均P＜0.05。(4)游泳应激组在海马[(46±95)％]和前额叶皮质[(65±24)％]的P-ERK2水平均低于空白对照组[分别为(76±30)%和(99±42)%],均P＜0．05。结论慢性强迫游泳应激能诱发大鼠的抑郁情绪,降低P-ERK2在海马和前额叶皮质的水平。     

慢性应激对大鼠海马CA3区锥体细胞形态结构的效应

目的　探讨慢性应激对大鼠海马CA3区锥体细胞形态结构的效应。方法　将 2 6只雄性Sprague Dawley大鼠随机分为对照组和应激组 ,每组 13只。采用尼氏 (Nissl)染色法、高尔基 (Golgi)镀染法和透射电镜技术 ,观察慢性强迫游泳应激对大鼠海马CA3区锥体细胞形态结构的效应。结果应激组大鼠海马CA3区锥体细胞数 (35 1± 3 9)较对照组 (38 7± 3 5 )明显减少 (P <0 0 5 ) ;顶树突的总长度为 (15 5 7± 33 3) μm ,较对照组 (195 6± 34 6 ) μm明显缩短 (P <0 0 5 )。应激组大鼠海马CA3区锥体细胞出现超微结构的改变 ,包括细胞固缩、体积缩小、核膜皱缩、线粒体变性和粗面内质网模糊不清。结论　慢性应激可引起海马CA3区锥体细胞形态和微细结构的改变及细胞丧失。     

抑郁模型大鼠脑内色氨酸及5-羟色胺的改变

目的研究慢性轻度不可预见性应激抑郁模型大鼠脑内色氨酸(TP)及5-羟色胺(5-HT)含量的变化,探讨抑郁障碍可能发病机制。方法将大鼠随机分为抑郁模型组(10只,以下简称抑郁组)和对照组(10只),对抑郁组大鼠进行连续21d的慢性应激。进行行为学观察;用高效液相色谱-荧光检测法测定大鼠脑内海马、前额叶、下丘脑和纹状体4个部位的5-HT及TP含量。结果(1)抑郁组大鼠慢性应激后的自主活动为(35±9)分,明显低于对照组的(73±9)分,差异有统计学意义(P<0.001)。(2)抑郁组大鼠海马、前额叶5-HT含量分别为(0.34±0.08)ng/mg组织和(0.55±0.06)ng/mg组织,均低于对照组[分别为(0.46±0.06)ng/mg组织和(0.66±0.09)ng/mg组织],差异均有统计学意义(P均<0.01);TP含量分别为(3.76±0.34)ng/mg组织和(4.08±0.51)ng/mg组织,均高于对照组[分别为(3.23±0.38)ng/mg组织和(3.49±0.44)ng/mg组织],差异均有统计学意义(P均<0.05)。两组大鼠下丘脑和纹状体5-HT及TP含量的差异均无统计学意义(P均>0.05)。结论脑内5-HT的合成功能降低是抑郁障碍的可能发病机制之一。     

慢性应激对大鼠海马CA1区长时程增强的影响及苯妥英钠的效应

目的　探讨慢性应激对海马功能的影响及苯妥英钠对它们的效应。方法　采用离体海马脑片结合电生理的方法 ,观察慢性应激对大鼠海马CA1区长时程增强 (LTP)的作用及苯妥英钠的效应。应用群体峰电位 (PS)的幅值和场兴奋性突触后电位 (fEP SP)的斜率作为观测LTP指标。在CA3区Schaffer侧支上施加高频刺激 (HFS) ,观察CA1区PS幅值和EPSP斜率在HFS前后的变化。结果　HFS后对照组和应激加苯妥英钠组LTP形成率、PS幅值和EPSP斜率变化的幅度均明显高于应激组和应激加生理盐水组 (P <0 0 5 )。对照组和应激加苯妥英钠组上述三个指标比较则无明显差异 (P >0 0 5 )。结论　慢性应激抑制海马CA1区LTP的形成 ,而苯妥英钠使应激海马LTP的形成保持在正常状态     

慢性应激对大鼠海马CA3区长时程增强的影响

目的　探讨慢性应激对大鼠海马CA3区长时程增强 (LTP)的影响及机制。方法　将 34只Wistar大鼠随机分成应激组 (8只 )、应激 +盐水组 (8只 )、应激 +MK 80 1组 (8只 )及空白对照组 (1 0只 ) ,应激刺激为饮水冲突模型 ,分别于实验初和LTP检测前 1天评定大鼠情绪性行为 ,在应激 1 5天后检测大鼠强直性LTP ,测量强直后 1 ,5 ,1 0 ,30 ,60 ,90 ,1 2 0minLTP群体峰电位幅度及峰潜期。结果(1 )应激前各组情绪性行为评分的差异均无显著性 ;应激后 ,应激 +盐水组 [(4 33± 0 50 )分 ]、应激 +MK 80 1组 [(3 60± 0 55)分 ]及应激组 [(2 90± 0 74)分 ]的评分均高于对照组 [(2 0 2± 1 1 6)分 ] ,差异有显著性 (P =0 0 0 0 ) ;(2 )应激组测试刺激阈值较对照组高 (45V∶30V) ;(3)在强直后第 1 ,90min时的LTP群体峰电位变化率应激组 [分别为 (2 1 1± 58) %和 (2 4 3± 69) % ]、应激 +盐水组 [分别为 (1 69±92 ) %和 (1 82± 1 61 ) % ]低于对照组 [分别为 (30 2± 2 1 0 ) %和 (30 3± 1 4 1 ) % ]和应激 +MK 80 1组 [分别为(375± 99) %和 (489± 2 36) % ] ,差异有显著性 (P <0 0 5) ,应激 +MK 80 1组与对照组的差异无显著性 ;(4)各应激组于各时点LTP峰潜期均较对照组长 ,但差异未呈显著性。结论　慢性     

视频脑电图在小儿癫痫诊断中的应用

目的评价视频脑电图(video-EEG)在小儿癫诊断中的应用价值。方法对126例具有发作性症状的患儿进行连续8h的包括清醒、睡眠、诱发试验及必要的认知测验的视频脑电图监测。结果经发作期视频脑电图证实,39例初诊为癫性发作的患儿中14例(35%)为非癫性发作;15例其他症状发作中13例(86%)为非癫性发作。64例样放电患儿中51例(80%)确定发作类型,22例(34%)确定癫类型。视频脑电图可发现短暂轻微的癫发作及样放电引起的一过性认知损伤。结论视频脑电图在排除非癫性发作、确定癫性发作的类型、评价脑电-临床关系方面可提供准确可靠的证据,进一步提高癫的临床诊断水平。     

Role of glutathione in repair of free radical damage in hippocampus in vitro.

Depletion of glutathione (GSH), an intrinsic antioxidant, increases vulnerability to free radical damage in a number of cell systems. This study investigates the role of GSH in limiting electrophysiological damage and/or recovery from free radical exposure in slices of guinea pig hippocampus. Synaptic potentials (PSPs) and population spikes (PSs) were recorded from field CA1. Free radicals were generated from 0.006% peroxide through the Fenton reaction. Analysis of the input-output curves showed that peroxide treatment decreased PSPs and impaired ability of the PSPs to generate PSs as previously reported. Recovery was nearly total within a half hour. Treatment with 5 mM buthionine sulfoximine (BSO) for 2 h depleted hippocampal GSH to 79.2% of control values. The extent of free radical damage was not increased. Recovery, however, was only partial. GSH was further depleted by oxidation with diamide or covalent bonding with dimethyl fumarate (DMF) immediately before and during the peroxide treatment. Neither diamide nor DMF treatment in BSO-incubated tissue enhanced peroxide-induced electrophysiological deficits. Following these treatments, however, tissue showed little recovery from free radical damage. We conclude that glutathione is essential for repair processes in hippocampal neurons exposed to oxidative damage.     

Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity

The pathogenesis of stroke, trauma and chronic degenerative diseases, such as Alzheimer's disease (AD), has been linked to excitotoxic processes due to inappropriate stimulation of the N-methyl-D-aspartate receptor (NMDA-R). Attempts to use potent competitive NMDA-R antagonists as neuroprotectants have shown serious side-effects in patients. As an alternative approach, we were interested in the anti-excitotoxic properties of memantine, a well-tolerated low affinity uncompetitive NMDA-R antagonist presently used as an anti-dementia agent. We explored in a series of models of increasing complexity, whether this voltage-dependent channel blocker had neuroprotective properties at clinically relevant concentrations. As expected, memantine protected neurons in organotypic hippocampal slices or dissociated cultures from direct NMDA-induced excitotoxicity. However, low concentrations of memantine were also effective in neuronal (cortical neurons and cerebellar granule cells) stress models dependent on endogenous glutamate stimulation and mitochondrial stress, i.e. exposure to hypoxia, the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+) or a nitric oxide (NO) donor. Furthermore, memantine reduced lethality and brain damage in vivo in a model of neonatal hypoxia-ischemia (HI). Finally, we investigated functional rescue (neuronal capacity to migrate along radial glia) by memantine in cerebellar microexplant cultures exposed to the indirect excitotoxin 3-nitropropionic acid (3-NP). Potent NMDA-R antagonists, such as (+)MK-801, are known to block neuronal migration in microexplant cultures. Interestingly, memantine significantly restored the number of neurons able to migrate out of the stressed microexplants. These findings suggest that inhibition of the NMDA-R by memantine is sufficient to block excitotoxicity, while still allowing some degree of signalling.     

Knowledge of management of epilepsy in young adults in Jordan

PURPOSE: Nationwide studies on public knowledge of epilepsy have been undertaken in several countries, but not in Jordan. The purpose of this study was to evaluate knowledge of the management of epilepsy in Jordan. METHODS: A cross-sectional study was performed during the period February-June 2005 on 16,044 individuals selected randomly to represent all regions of Jordan. Respondents were interviewed and asked to complete a five-item questionnaire testing their knowledge of the management of epilepsy. RESULTS: Most of the individuals (77.9%) agreed that patients with epilepsy are best treated in a specialized hospital for neurological diseases. Although the largest percentage of the sample (86.7%) agreed that the best person to treat epilepsy is a neurologist, others believed that a hypnotherapist (25.4%) or a religious healer (22.6%) is. As an immediate measure during an attack of epilepsy, most respondents (82.6%) agreed that protecting the patient's head is most important. During the postseizure period, 45.8% of respondents believed that offering the patient water or a cold or hot drink is appropriate. Two-thirds of the respondents (66.2%) agreed that epilepsy can be treated with drugs. Responses of the participants to the five items significantly differed with respect to age, gender, level of education, and occupation. CONCLUSION: Jordanians are reasonably well informed about most aspects of the management of epilepsy, but there is still a need for public education about this disorder.