1,6-二磷酸果糖对热性惊厥大鼠学习记忆和情感行为损害保护作用的研究

【目的】探讨1,6-二磷酸果糖(fructose-1,6-diphosphate,FDP)对大鼠热性惊厥性学习记忆和情感行为损害的保护作用。【方法】30只21日龄雄性SD大鼠随机均分为果糖干预(FDP intervention group,FD)、盐水对照(so-dium chloride solutin control group,NS)和热性惊厥组(febrile seizure group,FS)。水浴法建立热性惊厥模型;FD组于惊厥前30min腹腔注射FDP25mg/100g大鼠体重;而NS组腹腔注射相同体积的0.9%氯化钠溶液;FS组不予干预。观察各组在避暗试验(passive avoidance test,PAT)、Morris水迷宫(Morris water maze,MWM)及旷场试验(open field test,OFT)中学习记忆和情感行为的变化。【结果】FDP可使惊厥大鼠在PAT中的记忆潜伏期延长[FD组为(341.16±97.44)s,NS组为(227.62±92.19)s,FS组为(213.66±90.70)s,P<0.01],错误次数减少(FD组为1.84±1.27,NS组为4.97±1.18,FS组为5.06±1.38,P<0.01);在OFT中,FDP可增强反复惊厥大鼠的兴奋性(FD组得分为65.41±8.02,NS组为46.22±7.97,FS组为48.81±7.69,P<0.0 1),提高大鼠对陌生环境的适应能力(FD组后肢性站立的次数为36.29±5.06,NS组为18.72±4.71,FS组为20.06±4.96,P<0.01),改善大鼠的紧张情绪(FD组粪便粒数为5.62±2.76,NS组为10.79±2.91,FS组为11.43±3.01,P<0.01);在MWM中,FD组大鼠逃逸潜伏期缩短,搜寻策略改善。【结论】1,6-二磷酸果糖可以改善反复惊厥大鼠的学习记忆和情感行为,对惊厥性脑功能损伤具有保护作用。     

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目的探讨丰富环境对大鼠惊厥性脑损伤是否具有保护作用。方法2004-08西安交通大学医学院对30只21日龄雄性SD大鼠经水浴法诱导反复惊厥10次后随机均分为长程丰富环境暴露组(LG)、短程丰富环境暴露组(SG)和对照组(CG)。LG、SG组分别暴露于丰富环境中10d和5d,CG组不给予干预措施。观察各组大鼠在避暗试验(passiveavoidancetest,PAT)、Morris水迷宫(Morriswatermaze,MWM)及旷场试验(openfieldtest,OFT)中学习记忆和情感行为的变化。结果丰富环境暴露可使反复惊厥大鼠在PAT中的记忆潜伏期延长[LG组为(323·42±98·38)s,SG组为(276·52±92·64)s,CG组为(197·13±95·11)s,P<0·01],错误反应次数减少(LG组为1·75±1·01,SG组为2·14±1·13,CG组为5·37±1·26,P<0·01);在OFT中,丰富环境暴露可增强反复惊厥大鼠的兴奋性(LG组得分为62·35±7·81,SG组为53·67±7·66,CG组为45·48±7·34,P<0·01),提高大鼠对陌生环境的适应能力(LG组后肢性站立的次数为33·37±4·74,SG组为26·18±4·23,CG组为17·19±4·31,P<0·01),改善大鼠的紧张情绪(LG组粪便粒数为3·85±2·01,SG组为6·14±1·98,CG组为11·62±2·12,P<0·01);在MWM中,丰富环境暴露可使反复惊厥大鼠逃逸潜伏期缩短,搜寻策略改善(LG、SG及CG组直线式搜寻策略所占百分比依次为37·8%、33·6%及27·2%,χ2=41·02,P<0·005)。结论丰富环境暴露可以改善反复惊厥大鼠的学习记忆和情感行为,对惊厥性脑功能损伤具有保护作用。     

丰富环境暴露对大鼠惊厥性脑损伤保护作用的探讨

目的探讨丰富环境对大鼠惊厥性脑损伤是否具有保护作用。 方法2004 08西安交通大学医学院对30只21日龄雄性SD大鼠经水浴法诱导反复惊厥10次后随机均分为长程丰富环境暴露组(LG)、短程丰富环境暴露组(SG)和对照组(CG)。LG、SG组分别暴露于丰富环境中10d和5d，CG组不给予干预措施。观察各组大鼠在避暗试验(passive avoidance test,PAT)、Morris水迷宫(Morris water maze,MWM)及旷场试验(open field test,OFT)中学习记忆和情感行为的变化。 结果丰富环境暴露可使反复惊厥大鼠在PAT中的记忆潜伏期延长\[LG组为(32342±9838)s，SG组为(27652±9264)s，CG组为(19713±9511)s，P<001\]，错误反应次数减少(LG组为175±101，SG组为214±113，CG组为537±126，P<001)；在OFT中，丰富环境暴露可增强反复惊厥大鼠的兴奋性(LG组得分为6235±781，SG组为5367±766，CG组为4548±734，P<001)，提高大鼠对陌生环境的适应能力(LG组后肢性站立的次数为3337±474，SG组为2618±423，CG组为1719±431，P<001)，改善大鼠的紧张情绪(LG组粪便粒数为385±201，SG组为614±198，CG组为1162±212，P<001)；在MWM中，丰富环境暴露可使反复惊厥大鼠逃逸潜伏期缩短，搜寻策略改善(LG、SG及CG组直线式搜寻策略所占百分比依次为378%、336%及272%,χ2=4102,P<0005)。 结论丰富环境暴露可以改善反复惊厥大鼠的学习记忆和情感行为，对惊厥性脑功能损伤具有保护作用。     

纳洛酮对血管性痴呆大鼠学习记忆和海马神经细胞内钙离子的影响

目的:研究纳洛酮对血管性痴呆大鼠空间学习记忆能力的影响及可能机制。方法:结扎双侧颈总动脉制备血管性痴呆模型,随机分为假手术组、模型组和纳洛酮组。纳洛酮组于术后立即腹腔注射纳洛酮 0. 8mg·kg-1·d-1,连续 7d。8wk后用Morris水迷宫训练方法,比较 3组间学习记忆能力的差别。用激光共聚焦显微镜观察锥体细胞内钙离子荧光像素值。结果:模型组大鼠隐匿平台逃避潜伏期(EL)比假手术组大鼠明显延长 (P<0. 01),而空间探索实验穿越平台次数明显减少 (P<0. 01 );纳洛酮组大鼠EL较模型组明显缩短(P<0. 01),空间探索实验穿越平台次数明显增加 (P<0. 01)。此外,大鼠海马神经细胞内钙离子荧光像素值模型组(484±299)较假手术组 (135±29 )明显增高 (P<0. 01),而纳洛酮组 ( 139±31 )较模型组明显减低(P<0. 01)。结论:纳洛酮对血管性痴呆大鼠空间学习记忆减退有明显改善,其机制可能是与其防止海马神经细胞内钙离子增高有关。     

新型胆碱酯酶抑制剂对AD大鼠空间记忆及海马结构胆碱能纤维的影响

目的探讨新型胆碱酯酶抑制剂(NAI)及水迷宫训练对AD大鼠海马结构胆碱能纤维的影响。方法用36只Wistar♂大鼠制作AD动物模型,随机分成3组:NAI组、石杉碱甲组(Hup组)、单纯损伤组(SO组)。水迷宫训练后,采用组织化学方法测定海马结构胆碱能纤维密度。结果①定位航行实验中,NAI组逃避潜伏期较SO组显著缩短(P<0.01)。②空间探索实验中,NAI组跨越各象限平台相应位置次数占总次数百分率较SO组明显增高(P<0.01)。③组化结果显示:NAI组海马结构胆碱能纤维密度较SO组明显增加(P<0.05)。尽管NAI组胆碱能纤维密度高于Hup组,但无统计学意义。结论经NAI治疗及水迷宫行为训练后的AD大鼠,海马结构内胆碱能纤维密度明显增加,提示NAI及水迷宫训练联合作用可促进AD大鼠海马结构胆碱能纤维重建。     

Dissociation between the locomotor and anxiolytic effects of acetaldehyde in the elevated plus-maze: Evidence that acetaldehyde is not involved in the anxiolytic effects of ethanol in mice

Acetaldehyde, the first product of ethanol metabolism, has been suggested to play a major role in many behavioral effects of ethanol. However, very few studies have directly tested the behavioral effects of the acute administration of acetaldehyde. In particular, the role of this metabolite in ethanol-induced anxiolytic effects has never been extensively tested. The aim of the present study was to characterize the anxiolytic effects of acetaldehyde in two strains of mice, C57BL/6J and CD1 mice with the elevated plus-maze procedure. The results show that acute injections of ethanol (1–2 g/kg) induced significant dose-dependent anxiolytic effects in both strains of mice. In contrast, acetaldehyde failed to produce any anxiolytic effect, although it induced a significant hypolocomotor effect at the highest doses. In an independent experiment, cyanamide, an aldehyde dehydrogenase inhibitor, prevented the locomotor stimulant effects of ethanol, although it failed to alter its anxiolytic effects. Together, the results of the present study indicate that acetaldehyde is not involved in ethanol-induced anxiolytic effects, although it may be involved in its sedative/hypolocomotor effects.     

Evaluating the Benefit of Elevated Acoustic Output in Harmonic Motion Estimation in Ultrasonic Shear Wave Elasticity Imaging

Harmonic imaging techniques have been applied in ultrasonic elasticity imaging to obtain higher-quality tissue motion tracking data. However, harmonic tracking can be signal-to-noise ratio and penetration depth limited during clinical imaging, resulting in decreased yield of successful shear wave speed measurements. A logical approach is to increase the source pressure, but the in situ pressures used in diagnostic ultrasound have been subject to a de facto upper limit based on the Food and Drug Administration guideline for the mechanical index (MI <1.9). A recent American Institute of Ultrasound in Medicine report concluded that an in situ MI up to 4.0 could be warranted without concern for increased risk of cavitation in non-fetal tissues without gas bodies if there were a concurrent clinical benefit. This work evaluates the impact of using an elevated MI in harmonic motion tracking for hepatic shear wave elasticity imaging. The studies indicate that high-MI harmonic tracking increased shear wave speed estimation yield by 27% at a focal depth of 5?cm, with larger yield increase in more difficult-to-image patients. High-MI tracking improved harmonic tracking data quality by increasing the signal-to-noise ratio and decreasing jitter in the tissue motion data. We conclude that there is clinical benefit to use of elevated acoustic output in shear wave tracking, particularly in difficult-to-image patients.     

水迷宫训练逆转孕期应激造成的子代海马NR2B表达的降低

目的:比较空间学习记忆中孕期应激子代和对照组子代海马空间学习功能密切相关蛋白NR2B的表达。方法:建立孕期束缚应激小鼠模型,在出生后第3周用酶联免疫法检测子代雄性小鼠血清皮质酮;在出生后第9周,采用免疫蛋白印迹和real-timePCR法检测子代雄性小鼠非空间学习记忆状态及空间学习记忆中海马NR2B的表达水平。结果:(1)基础状态下孕期应激子代血清皮质酮水平与对照组子代并无差异,应激状态下孕期应激子代血清皮质酮水平(43.7×104pg/ml)明显高于对照组子代(18.7×104pg/ml);(2)孕期应激雄性子代在出生后第9周海马NR2B mRNA和蛋白表达均显著低于对照组雄性子代。但经过空间学习记忆训练,两组海马NR2B蛋白水平无明显差异。结论:孕期应激减少子代海马神经元NR2B的表达,但水迷宫行为训练可逆转孕期应激造成的子代海马神经元NR2B的表达降低。     

SB‐334867, an orexin receptor 1 antagonist,decreased seizure and anxiety in pentylenetetrazol‐kindled rats

Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system (CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin‐A and orexin‐B are brain neuropeptides originating from postero‐lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, this study was designed to evaluate the effect of OX1 receptor antagonist (SB‐334867) on seizure‐ and anxiety‐related behaviors of pentylenetetrazol (PTZ)‐kindled rats. Kindling was induced by repeated intraperitoneal (IP) injections of PTZ (32 mg/kg) with two‐day intervals for 24 days in male Wistar rats. Three groups received intracerebroventricular (ICV) injections of SB‐334867 (2.5, 5, and 10 μg/rat) before PTZ injections. Two control groups received vehicle (2 μL/rat, ICV) and valproate (26 μg/rat, ICV) before PTZ injections. An extra group of control animals received saline both ICV and IP. Seizure‐related behaviors were monitored for 30 min following PTZ administration. The anxiety‐like behaviors were also assessed using elevated plus‐maze in the first and last days of the study. The results revealed that ICV injection of SB‐334867, mainly at the dose of 10 μg/rat, decreased the median of seizure stages, prolonged the latency and reduced the duration of different seizure stages, and reversed the PTZ‐induced anxiety‐like behaviors. Based on the presented results, it is suggested that pharmacological blockade of the OX1 receptor is a potential target in the treatment of seizure and concomitant anxiety disorders.