丙戊酸钠对慢性应激大鼠认知行为的影响

丙戊酸钠(VPA)是一种经典的抗癫痫药物,在精神科作为心境稳定剂广泛应用于临床.许多研究发现,VPA具有营养神经的保护作用[1],而国内关于VPA能否改善认知行为的研究较少.本研究采用VPA干预慢性应激模型大鼠,了解其对大鼠认知行为的影响.     

丙戊酸钠脑病1例报告

1临床资料患者,男,45岁,农民。以"反映迟钝2d,呼之不应1d"为代主诉于2011-03入院。既往史:30a前开始出现癫发作,为全面大发作,发作较为频繁,几乎每月均有发作,智能下降,近日又频繁出现"失神发作",入院3d前口服"丙戊酸钠(VPA)+卡马西平"治疗;否认高血压、糖尿病、冠心病,无脑外伤、脑炎等病史,无烟酒嗜好。现病史:患者于入院前开始出现反应迟钝,精神差,能简单交流,并逐渐出现意     

丙戊酸钠的应用进展

本文对丙戊酸钠的抗痫机制及用量进行了综述,详述了丙戊酸钠的临床应用,与卡马西平、苯妥英钠的相互作用及不良反应。     

丙戊酸钠预防性治疗偏头痛的临床研究

丙戊酸钠(Sodium Valproate简称NaVPA)是一种有效的抗惊厥药物。最近有报道NaVPA用于预防偏头痛发作有较好的疗效,我们自1990年8月起,对43例偏头痛患者用NaVPA治疗取得了较满意的效果,结果报告如下。     

丙戊酸钠对精神分裂症攻击行为的治疗作用

目的：了解丙戊酸钠对精神分裂症患者攻击性行为的治疗作用。方法：对21例有攻击性行为的长期住院精神分裂症患者在原有抗精神病药的基础上加用丙戊酸钠进行为期6周的治疗，在治疗前及治疗后第6周用简明精神病评定量表(BPRS)、外显攻击行为量表修订版(MOAS)进行评定。结果：治疗前后BPRS各因子分差异无显著性。但治疗后MOAS评分显著降低。结论：丙戊酸钠辅助治疗精神分裂症的攻击性行为安全有效。     

丙戊酸钠联用利培酮继发丙戊酸钠相关性高血氨脑病1例

1 病例资料 36岁男性,因发作性意识丧失伴四肢抽搐24年余入院.多家医院确诊为难治性癫痫,长期服用卡马西平(早0.4 g,晚0.4 g)联合丙戊酸钠(valproate,VPA;早0.75 g,晚0.75 g)治疗,仍间断发作.入院体格检查:神志清楚,智力下降,认知功能基本正常,未发现明显神经系统阳性体征.     

丙戊酸钠对氯氮平血药浓度和疗效的影响

目的:探讨合用丙戊酸钠对氯氮平治疗精神分裂症时的血药浓度和疗效的影响。方法:将80例男性精神分裂症患者随机分为两组,单用组40例患者单服氯氮平,合用组40例患者同时服用氯氮平及丙戊酸钠,分别于治疗前、治疗1周和4周末测定氯氮平的血药浓度,同时评定阳性与阴性症状量表(PANSS)、治疗中出现的症状量表(TESS)。结果:合用组治疗1周和4周末有部分患者氯氮平血药浓度升高,部分患者降低,与基线期相比,治疗4周末有显著降低。结论:合用丙戊酸钠后氯氮平血药浓度治疗4周末显著降低;丙戊酸钠可以提高氯氮平对阳性症状的疗效。     

丙戊酸钠和卡马西平对脑电图的影响

目的：探讨丙戊酸钠（ＶＰＡ）和卡以西平（ＣＢＺ）对脑电图的影响。方法：对３９例单独应用ＶＰＡ和３５例单独应用ＣＢＺ，临床发作已被控制的两组病例进行脑电图描记和分析。结果：ＶＰＡ治疗治疗组，７２％的病例发作间歇期痫样放电消失或明显减少，而ＣＢＺ治疗后，仅４９％消失或明显减少。结论：ＣＢＺ可使临床发作控制，但却有２０％的病例痫放电增加，但在ＶＰＡ治疗者则未见此现象。ＶＰＡ对脑电背景活动影响不明显，而Ｃ     

大脑镰旁脑膜瘤术后丙戊酸钠中毒1例

正颅脑手术,特别是幕上开颅手术,为预防术后癫痫常预防性应用抗癫痫药物,而丙戊酸钠是临床上最常用的预防和控制癫痫的药物之一。本文报道大脑镰旁脑膜瘤术后丙戊酸钠严重中毒1例。1病例资料55岁女性,因头晕、左侧肢体乏力1个月入院。入院体格检查:左侧肢体肌力约4级,未发现其他神经系统阳性体征。入院后头部MRI检查示右侧大脑镰旁占位,大小约3cm×4 cm,位于右侧中央前回前方,且中央前回向后外侧受压明显,考虑脑膜瘤。常规预防癫痫治疗(口服丙戊酸钠缓释片,0.5 g,2次/d)。     

丙戊酸钠对精神分裂症幻听症状的辅助疗效

目的：探讨丙戊酸钠对精神分裂症患者的幻听症状有无辅助治疗作用。方法：将病人随机分为两组，一组氯丙嗉合合并丙戊酸钠治疗8周，另一组不合并丙戊酸钠治疗。用简明精神病评定量表（BPRS）、阳性症状评定量表（SAPS）、临床疗效总评量表（CGI）及副反应量表（TFSS）综合评定。结果：氯丙嗪合并丙戊酸钠治疗组疗后BP民分、单项幻觉分，以及SAPS总分、幻觉分、幻听分均低于不合并治疗组，尤以1、2周末明显。结论：丙戊酸钠可加快精神分裂症病人幻听症状的消除，且对幻听伴随的焦虑、激越、怪异行为、敌对猜疑等症状亦有一定的疗效。     

Vanadium exposure-induced striatal learning and memory alterations in rats

Occupational and environmental exposure to vanadium has been associated with toxicities in reproductive, respiratory, and cardiovascular systems. The knowledge on whether and how vanadium exposure caused neurobehavioral changes remains incomplete. This study was designed to investigate the changes in learning and memory following drinking water exposure to vanadium, and to conduct the preliminary study on underlying mechanisms. Male Sprague-Dawley rats were exposed to vanadium dissolved in drinking water at the concentration of 0.0, 0.5, 1.0 and 2.0 g/L, as the control, low-, medium-, and high- dose groups, respectively, for 12 weeks. The results by the Morris water maze test showed that the time for the testing animal to find the platform in the high exposed group was increased by 82.9% and 49.7%, as compared to animals in control and low-dose groups (p < 0.05). There were significantly fewer rats in the medium- and high- dose groups than in the control group who were capable of crossing the platform (p < 0.05). Quantitation of vanadium by atomic absorption spectrophotometry revealed a significant dose-dependent accumulation of vanadium in striatum (r = 0.931, p < 0.01). Histopathological examination further demonstrated a degenerative damage in vanadium-exposed striatum. Interestingly, with the increase of the dose of vanadium, the contents of neurotransmitter ACh, 5-HT and GABA in the striatum increased; however, the levels of Syn1 was significantly reduced in the exposed groups compared with controls (p < 0.05). These data suggest that vanadium exposure apparently reduces the animals’ learning ability. This could be due partly to vanadium’s accumulation in striatum and the ensuing toxicity to striatal structure and synaptic plasticity. Further research is warranted for mechanistic understanding of vanadium-induced neurotoxicity.     

神经生长因子对脑缺血大鼠学习与记忆的影响

目的为了观察神经生长因子（NGF）对脑缺血大鼠学习与记忆的影响和海马内N-甲基-D-天门冬氨酸受体NR2A/B亚zhanghaopeng（NR2A/B）表达的变化。方法本研究将48只成年雄性SD大鼠分为正常组（n=12）、假手术组（n=12）、慢性脑缺血组（n=12）、NGF处理组（n=12）。于造模后开始腹腔注射0.25 ug/100 g NGF,假手术组和慢性脑缺血组腹腔注射等量生理盐水,均1次/d,共21 d。用Morris水迷宫和＂＂Y＂迷宫作业测试其空间学习与记忆成绩,再采用Western blot方法分析海马的NR2A、NR2B的表达。结果①Morris水迷宫测试：模型组大鼠寻找平台的潜伏期较假手术组明显延长,NGF处理组大鼠寻找平台的潜伏期较模型组明显缩短;＂Y＂迷宫测试：模型组大鼠学会躲避电击的正确次数较假手术组明显减少,NGF处理组大鼠学会躲避电击的正确次数较模型组明显增多;②模型组NR2A表达水平较假手术组明显降低,而NR2B明显升高;NGF处理组海马内NR2A表达水平较模型组明显上调,而NR2B明显下调。结论神经生长因子可增强学习与记忆,海马内N-甲基-D-天门冬氨酸（NMDA）受体表达变化可能是影响学习与记忆的机制之一。     

戊四氮致痫大鼠学习记忆改变及海马CA_1和CA_3区神经颗粒素的表达变化

目的 探讨戊四氮慢性点燃癫痫对大鼠学习记忆能力的影响及海马CA_1、CA_3区神经颗粒素(neu-rogranin,Ng)的表达变化.方法 采用戊四氮(pentylenetetrazole,PTZ)腹腔注射慢性点燃癫痫(chronic epileptic,CEP)模型,用Morris水迷宫和Y迷宫对大鼠进行学习记忆能力检测,运用免疫组织化学方法测定大鼠海马CA_1、CA_3区Ng的表达变化.结果 与对照组比较,慢性癫痫发作组大鼠在水迷宫中的逃避潜伏期延长(P<0.01),穿越平台次数减少(P<0.01),在Y迷宫中的错误反应次数增多(P<0.05).在海马CA_1区Ng的免疫反应强度减弱(P<0.05),CA_3区两组比较差异无统计学意义.结论 戊四氮慢性点燃癫痫大鼠学习记忆能力受损,海马CA_1区Ng表达减少可能参与了这一过程.

Abstract：

Objective To explore the effect of Pentylenetetrazole (PTZ)-kindled epilepsy on rats' learning and memory and the expression of neurogranin(Ng) in hippocampal CA_1 and CA_3. Methods Use chronic model of epilepsy induced by PTZ intraperitoneal injection. The ability of learning and memory were assessed by the Morris water maze and Y maze. The expression of Ng in hippocampal CA_1 and CA_3 was determined by immunocytochemical method respectively. Resuits The learning and memory ability of the epilepsy rats was impaired. Meanwhile,The immunological reaction of Ng for CEP group at CA_1 was weaker than NC group, but it made no difference at CA_3. Conclusion The impairment of learning and memory ability of the epilepsy rats might be related with the changes of Ng in hippocampal CA_1.     

Deprivation of endogenous brain-derived neurotrophic factor results in impairment of spatial learning and memory in adult rats

Brain-derived neurotrophic factor (BDNF) is abundantly expressed in the hippocampus and cerebral cortex and is involved in synaptic plasticity and long-term potentiation (LTP). The present study was under taken to investigate whether endogenous BDNF was required for spatial learning and memory in a rat model. Antibodies to BDNF (anti-BDNF, n=7) or control immunoglobulin G (control, n=6) were delivered into the rat brain continuously for 7 days with an osmotic pump. The rats were then subjected to a battery of behavioral tests. The results show that the average escape latencies in the BDNF antibody treated group were dramatically longer than those of the control (F=13.3, p<0.001). The rats treated with control IgG swam for a significantly longer distance in the P quadrant (where the escape plane had been placed) compared with the other three quadrants (p<0.05). In contrast, anti-BDNF-treated rats swam an equivalent distance in all four quadrants. The average percentage of swimming distance in the P quadrant by anti-BDNF-treated rats was much less than that by control IgG treated rats (p<0.001). These results suggest that endogenous BDNF is required for spatial learning and memory in adult rats.     

Chronic epigallocatechin-3-gallate ameliorates learning and memory deficits in diabetic rats via modulation of nitric oxide and oxidative stress

Due to anti-diabetic and antioxidant activity of green tea epigallocatechin gallate (EGCG) and the existence of evidence for its beneficial effect on cognition and memory, this research study was conducted to evaluate, for the first time, the efficacy of chronic EGCG on alleviation of learning and memory deficits in streptozotocin (STZ)-diabetic rats. Male Wistar rats were divided into control, diabetic, EGCG-treated-control and -diabetic groups. EGCG was administered at a dose of 20 and 40 mg/kg/day for 7 weeks. Learning and memory was evaluated using Y maze, passive avoidance, and radial 8-arm maze (RAM) tests. Oxidative stress markers and involvement of nitric oxide system were also evaluated. Alternation score of the diabetic rats in Y maze was lower than that of control and a significant impairment was observed in retention and recall in passive avoidance test (p < 0.01) and EGCG treatment (40 mg/kg) of diabetic rats significantly improved these parameters (p < 0.05). Also, diabetic animals exhibited fewer correct choices (p < 0.01) and more errors (p < 0.005) in the RAM task and EGCG (40 mg/kg) significantly ameliorated these changes (p < 0.05). Further, pretreatment with l-arginine as a substrate for nitric oxide synthase (NOS) and/or 7-nitroindazole as a neuronal NOS inhibitor attenuated and potentiated the beneficial effect of EGCG regarding learning and memory respectively. Meanwhile, increased levels of malondialdehyde (MDA) and nitrite in diabetic rats significantly reduced due to EGCG treatment (p < 0.05). In summary, chronic green tea EGCG dose-dependently could ameliorate learning and memory deficits in STZ-diabetic rats through attenuation of oxidative stress and modulation of NO.     

行为训练对双侧海马梗死大鼠学习记忆与NCAM的影响

目的探讨行为训练对双侧海马梗死大鼠空间学习记忆功能恢复及海马神经细胞粘附因子(NCAM)的影响及其作用机制。方法30只SD大鼠采用光化学诱导法制作双侧海马CA1区梗死模型,于24h后随机分为行为训练组和制动组,于造模3d后分别给予行为训练或制动,在大鼠造模后3d、行为训练后7d、14d和21d时进行学习记忆能力测试。并于不同时间取脑进行免疫组织化学染色,观察其梗死灶海马周围NCAM含量的变化。结果行为训练组学习记忆能力评估均优于制动组(P<0.05),海马NCAM含量均较制动组增多。结论行为训练可促进大鼠空间学习记忆能力的恢复,其作用机制可能与海马NCAM的增多有关。     

Let-7c-1对戊四氮致痫大鼠学习记忆功能的作用

目的研究let-7c-1对戊四氮(pentylenetetrazol,PTZ)致痫大鼠学习记忆功能的影响,探讨其可能机制。方法通过PTZ腹腔注射SD雄性大鼠建立慢性癫痫模型,随机分为癫痫组、干预对照组、let-7c-1激动剂组,各组12只,另设12只大鼠为正常组。28 d后,观察各组大鼠的行为学变化,let-7c-1基因表达及大鼠海马组织中Bcl-2、Caspase3蛋白的表达。结果与正常组相比,癫痫组大鼠逃避潜伏期延长、穿越平台次数减少、在目标象限的总路程缩短,差异有统计学意义(P0.05);癫痫组与干预对照组相比,逃避潜伏期、穿越平台次数、在目标象限的总路程无统计学差异(P0.05);与干预对照组相比,let-7c-1激动剂组逃避潜伏期明显延长,穿越平台次数减少、在目标象限的总路程缩短,差异有统计学意义(P0.05)。干预对照组与let-7c-1激动剂组let-7c-1基因相对表达量分别为(1.35±0.32)、(62.53±21.01)(F=50.97,P0.05)。癫痫组let-7c-1基因表达量高于正常组,差异有统计学意义(P0.05)。let-7c-1激动剂组let-7c-1基因表达量明显高于干预对照组、癫痫组及正常组,差异有统计学意义(P0.05)。与正常组相比,癫痫组的Bcl-2蛋白表达减少,Caspase3蛋白表达增加,差异有统计学意义(P0.05);癫痫组与干预对照组相比,Bcl-2蛋白及Caspase3蛋白的表达无统计学差异(P0.05)。与干预对照组相比,let-7c-1激动剂组Bcl-2蛋白表达明显减少,Caspase3蛋白表达明显增加,差异有统计学意义(P0.05)。结论 Let-7c-1可能通过减少海马组织Bcl-2蛋白及增加Caspase-3蛋白表达使PTZ致痫大鼠的学习记忆功能受损。     

慢性脑缺血海马CA1区HCN1蛋白表达下调与学习记忆损伤研究

目的 探讨慢性脑缺血导致大鼠认知功能障碍与HCN1通道亚型蛋白表达变化的内在关系。方法 健康成年雄性SD大鼠20只,随机分为假手术组、缺血组,每组各10只。各组缺血4周后采用Morris水迷宫检测大鼠学习记忆功能,免疫组化检测HCN1表达水平,进一步用蛋白印迹检测HCN1蛋白表达水平。结果 与假手术组相比,缺血组大鼠逃避潜伏期明显延长(P<0.05); 缺血组大鼠海马CA1区HCN1蛋白表达水平明显降低,与模型组比较有明显差异(P<0.05)。结论 慢性脑缺血海马CA1区存在HCN1通道亚型表达下调且参与大鼠认知功能损伤,可能为治疗慢性脑缺血所致认知功能障碍的新靶点。     

学习记忆能力下降大鼠神经细胞增殖的研究

目的　观察学习记忆能力减退老年大鼠海马齿状回神经细胞的增殖。方法　Morris水迷宫筛选出学习记忆能力减退大鼠 (痴呆组 )与正常大鼠 (对照组 )。BrdU标记海马齿状回增殖细胞。TUNEL法标记DNA片段原位检测凋亡细胞。计数海马颗粒细胞层与海马门的BrdU阳性细胞与凋亡细胞数。结果　痴呆组与对照组大鼠相比 ,海马颗粒细胞层BrdU阳性细胞显著增加 (P <0 0 1) ,而凋亡细胞数无显著差异 (P >0 0 5 )。海马门BrdU阳性细胞数及凋亡细胞数均无显著差异 (P >0 0 5 )。结论　学习记忆能力减退的老年大鼠海马齿状回神经细胞增殖能力减低。     

The effect of steroid sulfatase inhibition on learning and spatial memory

Steroid sulfatase inhibitors can enhance the concentration of the neurosteroid DHEAS in rat brain. Previous studies have demonstrated that the steroid sulfatase inhibitor (p-O-sulfamoyl)-N-tetradecanoyl tyramine (DU-14) could reverse scopolamine induced amnesia in rats in a passive avoidance memory paradigm. The intent of this study was to determine whether chronic pretreatment with DU-14 could reverse scopolamine amnesia and/or enhance spacial memory in the place, probe and cued versions of the Morris water maze (MWM). Rats were divided into four groups and administered IP for 15 days either DU-14 (30.0 mg/Kg) or corn oil (1.0 ml/Kg) vehicle. On training days animals were administered either scopolamine (1.0 mg/Kg) or saline (1.0 ml/Kg). The groups administered DU-14 displayed a significant enhancement in learning and spacial memory in the place version of the MWM, when compared to respective vehicle-scopolamine and vehicle-saline groups. In the probe version, the DU-14-saline group remained in the target quadrant of the maze significantly longer than any of the other groups indicating enhanced retention. In the cued version of the MWM, treatment with DU-14 did not significantly change escape latency suggesting that the steroid sulfatase inhibitor did not alter motivation or locomotion. These results suggest that the chronic administration of steroid sulfatase inhibitors enhance learning and spatial memory in rats.