全脑照射后血脑屏障改变对放射性脑损伤的影响

目的 探讨全脑照射后血脑屏障通透性的改变对放射性脑损伤的影响.方法 80只昆明小鼠随机分对照组、5 Gy、15 Gy和30 Gy剂量组,每组20只,分别于照射后1周和4周,各组随机取出10只小鼠采用Morris水迷宫测试其空间记忆能力,行为测试结束后,随机抽取7只测量其脑内伊文思蓝的含量,3只在电镜下观察血脑屏障结构的改变.结果 照射后1周,15 Gy和30 Gy剂量组脑内依文思蓝明显升高;照射后4周,15 Gy剂量组恢复到对照组水平,而30 Gy剂量组仍未见恢复.照射后1周,15 Gy和30 Gy剂量组小鼠第1次穿越平台的时间延长和穿越次数明显减少;照射后4周,15 cy剂量组恢复到对照组水平,而30 Gy剂量组仍未见恢复.电镜结果显示15 Gy剂量组照射后1周血脑屏障基膜周围出现透亮区,照射后4周恢复;30 Gy剂量组照射后1周血脑屏障基膜周围也出现透亮区,而照射后4周除血脑屏障基膜继续透亮区外,尚出现内皮细胞核固缩、神经元凋亡和脱髓鞘等现象.结论 放射后血脑屏障的通透性的改变是放射损伤的结果,可能也是放射后继发性脑损伤的原因.     

多巴胺受体功能与老年鼠工作记忆的关系

目的 探讨多巴胺（ＤＡ）受体功能与工作记忆的关系。方法 测试２８只雄性ＳｐｒａｎｇｕｅＤａｗｌｅｙ老年鼠在１５臂放射状迷宫中的操作成绩。观测ＤＡ受体配体对操作成绩的影响。结果（１）适量的Ｄ１受体激尖剂二羟西汀（０．６ｍｇ／ｋｇ）直接作用或低量的Ｄ２类受体拮抗剂氟哌淀醇（０．１ｍｇ／ｋｇ）通过Ｄ２突触前受体作用均可改善Ｄ１受体功能而提高工作记忆能力;而Ｄ１受体拮抗剂ＳＣＨ２３３９０（０．０１ｍｇ／ｋ     

用Morris全自动水迷宫评价Sprage Dawley鼠全脑反复缺血后学习记忆功能研究

目的　评价大鼠脑缺血后的学习、记忆功能及其与海马组织学变化的关系。方法　用Morris全自动新式水迷宫试验方法对反复脑缺血再灌注大鼠进行学习获得试验、记忆保持试验 ,光镜观察海马组织学变化 ,并计算海马神经元密度。结果　与对照组比较 ,反复脑缺血大鼠学习记忆成绩显著下降 ,潜伏期显著延长 ,游水迷宫形呈周边型 ;缺血后海马CA1、CA4 和PM区神经元大量丧失。结论　大鼠反复脑缺血出现严重的学习、记忆障碍。认知功能改变与海马神经元缺血性损害有关。用Morris全自动水迷宫评价缺血所致学习、记忆障碍简便、准确、真实。     

大鼠脑伤后神经行为和记忆障碍的实验研究

大鼠脑伤后神经行为和记忆障碍的实验研究刘信龙，江基尧，杨中坚，戴莉萍一、材料和方法１．液压装置由圆形液柱、打击架、示波器和压力传感器组成。圆柱一端为活塞，另一端接打击管和压力传感器。在致伤时整个管道系统充满３７℃生理盐水后密闭。打击锤打击活塞后产生的...     

葛根素对大鼠全脑缺血再灌注后学习记忆障碍保护作用及其机制的研究

目的 探讨葛根素对大鼠全脑缺血再灌注后学习记忆能力的影响及其机制。方法 采用四血管阻断法建立SD大鼠全脑缺血再灌注损伤模型，暗回避反应法测定学习记忆能力，并应用免疫组织化学法、原位末端标记法，检测大鼠全脑缺血再灌注海马CA，区的bcl-2阳性细胞数、凋亡细胞数的动态变化。结果 (1)与再灌注组相比，葛根素组大鼠潜伏期明显延长；(2)脑缺血再灌注后，海马CA1区bcl-2蛋白的表达随再灌注时间不同而变化，缺血20min后再灌注24h达高峰，葛根素组bcl2蛋白的表达于相应的时间点明显增多；(3)脑缺血再灌注后海马CA1区神经元凋亡损伤在再灌注72h损伤最重，葛根素组可减少相应时点神经细胞凋亡数。结论 葛根素对全脑缺血再灌注后大鼠学习记忆能力具有明显的改善作用，其作用机制可能与通过上调bcl-2基因表达从而抑制或延迟脑缺血再灌注后细胞凋亡有关。     

丁香酚不同途径给药对昆明鼠的空间学习记忆的研究

目的 探讨丁香酚不同途径给药对昆明鼠的空间学习记忆的影响.方法 通过灌胃、嗅觉吸人和鼻腔滴入等不同途径给予丁香酚,用自主活动箱测定小鼠神经兴奋性以及用水迷宫测定小鼠空间学习记忆能力.结果 灌胃组、嗅觉吸人组、鼻腔滴人组的自主活动明显高于空白组小鼠自主活动;丁香酚嗅觉吸入组的水迷宫潜伏期明显小于空白组的水迷宫潜伏期.结论丁香酚通过嗅觉吸入的途径能更好地改善小鼠的学习记忆功能.     

神经干细胞植入阿尔茨海默病鼠脑后的效果观察

神经干细胞移植治疗阿尔茨海默病鼠包括细胞替代治疗和基因治疗,神经干细胞移植阿尔茨海默病鼠脑后其组织形态学与行为学效应均可以得到不同程度的修复和改善。细胞替代治疗中,神经干细胞与神经营养因子联合移植效应优于单纯的神经干细胞移植,但目前对神经干细胞体内分化机制的不确定导致了神经干细胞移植治疗的盲目性,同时对影响其疗效的各种可能因素也缺乏比较研究。神经干细胞基因治疗具有细胞替代和基因治疗的双重作用,但尚处于研究的初期阶段,仍以NGF,BDNF,GDNF等单一营养因子基因修饰的神经干细胞移植治疗为主,且转基因神经干细胞移植入阿尔茨海默病鼠脑后外源基因表达效率、促分化、功能修复情况以及安全性的研究还很缺乏。目前神经干细胞移植治疗阿尔茨海默病鼠脑后的疗效检测技术手段比较单一,免疫组化方法与活体示踪技术的结合、形态学指标与功能学指标的综合检测是疗效检测的发展趋势。     

母鼠孕期γ-射线照射及新生鼠脑冰冻损伤后皮质发育障碍的模型研究

目的建立Wistar大鼠大脑皮质损伤后发育障碍的动物模型。方法分别采用γ射线照射孕15dWistar大鼠和用低于-50℃的液氮探子冰冻损伤新生第2天(P2)幼鼠脑皮质的方法制作皮质发育障碍动物模型。观察:(1)孕鼠后代及脑冰冻损伤幼鼠皮质发育障碍的类型和发生率,病理检查大鼠脑皮质和海马神经元结构;(2)模型组和正常对照组大鼠日常活动能力及脑电图变化;(3)利用热水浴诱导惊厥发作,观察潜伏期;(4)采用Morris水迷宫法测试大鼠学习能力和空间记忆能力。结果(1)两模型组大鼠脑重量(分别为平均932mg和927mg)均低于正常对照组大鼠(平均1300mg,P<0.05),病理切片可见大脑皮质变薄,皮质层状结构紊乱,具有多灶性、局灶性4层结构,皮质下神经元呈结节状异位,海马锥体神经元呈团状分布;(2)模型鼠日常活动能力较差;(3)模型组热水浴诱导惊厥发作的潜伏期缩短[3组大鼠分别为(3.65±0.44)min、(3.47±0.48)min和(4.66±0.58)min,P<0.05];(4)模型组水迷宫实验中寻找水下平台时间延长(P<0.05)。结论用γ射线照射孕15d大鼠和冰冻损伤P2幼鼠大脑皮质均可建立皮质损伤后发育障碍的动物模型,其发作易患性增加,伴有认知功能障碍。     

轻度颅脑损伤中应激因素对大鼠学习记忆的影响

目的探讨应激因素(惊吓)对轻度脑损伤大鼠恢复期学习记忆的影响。方法将30只实验大鼠随即分为损伤组、惊吓组与正常对照组。对Hall[1]脑损伤装置进行改进,制造清醒状态下大鼠轻度脑损伤模型。伤前3d及伤后10d通过Morris水迷宫试验检测损伤组、惊吓组与对照组学习记忆能力的差异。结果损伤组、惊吓组学习记忆能力与对照组比较有统计学意义(P<0.05),损伤组与惊吓组之间比较无统计学意义(P>0.05)。结论在轻度颅脑损伤中应激因素对学习记忆改变有重要意义。     

大鼠颞叶癫痫发作后学习记忆障碍与海马神经元内游离钙离子浓度变化的相关性研究

目的探讨大鼠颞叶癫痫发作后不同时间段学习记忆障碍程度与海马神经元内游离钙离子（[Ca^2＋]）浓度变化的相关性。方法立体定向方法建立大鼠颞叶癫痫模型后用Morris水迷宫实验评价不同时间段大鼠学习记忆障碍程度；利用钙离子探针Fluo-3／AM在激光扫描共聚焦显微镜下检测癫痫发作后不同时间段海马神经元内[Ca^2＋]i的变化。结果大鼠颞叶癫痫发作后均出现不同程度的学习记忆障碍，随发作时间的延长逐渐加重，发作2月后达到高峰。颞叶癫痫发作后右侧海马神经元内[Ca^2＋]i的荧光强度明显升高，6h达到高峰，发作2月内保持在较高水平，与正常对照组和注射生理盐水组比较有显著性差异（P〈0．05），而3月后则有下降并低于正常对照组的趋势；对侧海马神经元内[Ca^2＋]i的荧光强度高于正常对照组和注射生理盐水组，但低于右侧海马神经元内[Ca^2＋]i的荧光强度。结论大鼠颞叶癫痫发作后的学习记忆障碍随发作时间延长而加重，发作2月后达到最严重，与海马神经元内[Ca^2＋]i变化具有一定的时间相关性。     

慢性前脑缺血大鼠学习、记忆功能的研究

目的 研究慢性持续性脑血流量下降对大鼠学习、记忆功能的影响。方法 采用双侧颈总动脉永久结扎方法制备慢性前脑缺血动物模型；利用激光多普勒血流仪检测各组大鼠术后不同时间点（术后24h、7d、15d、30d、60d、90d、120d）额叶皮质、海马枢局部及血流量(rCBF）；采用被动回避性条件反射－－跳台试验检验各组大鼠（时间点同前）学习能力；利用水迷宫方法检验各组大鼠记忆功能。结果 大鼠术后额叶皮质、海马区的cCBF明显下降，以术后24h最明显，主后120d时仍明显 于正常，呈慢性持续性下降的趋势。同时各实验组大鼠学习、记忆能力也明显下降，且有随时间推移而逐渐加重的倾向。结论 慢性持续性脑血流量下降可导致实验大鼠出现进行性认知功能障碍。     

DNA甲基化调控学习和记忆功能的研究进展

学习和记忆是两项最基本的认知功能,但其分子基础目前仍然没有研究清楚.神经细胞发挥功能主要依靠基因表达多种蛋白,而DNA甲基化修饰是一种调控基因表达的重要表现遗传方式.在正常衰老的过程中,全基因组DNA甲基化程度发生下降,与此同时学习和记忆功能也下降,这揭示DNA甲基化神经元可能参与记忆编码.然而这也缺乏直接支持的证据.由此几项研究已经提供了重要的支持证据,且DNA甲基化与记忆形成的研究得到了广泛的关注.为了进一步探索学习与记忆的表观遗传学机制,我们对近年来NA甲基化调控学习和记忆功能的研究进展作了综述.     

转基因鼠载脂蛋白E基因表达异常对学习和记忆能力的影响

】     

Potential consequences of altered neurogenesis on learning and memory in the epileptic brain

Studies of epilepsy and memory are tied by their common dependence on the hippocampal formation and the adjacent brain structures in the temporal lobe. With the discovery of adult neurogenesis and the consequent revisions of our understanding of how the hippocampus works, the role of neurogenesis in epilepsy needs to be addressed. In this article, we outline two theories describing how neurogenesis contributes to the hippocampus-dependent learning. We speculate that any drastic changes in neurogenesis will negatively impact the hippocampal memory processing.     

Dynamic switching between semantic and episodic memory systems

It has been suggested that episodic and semantic long-term memory systems interact during retrieval. Here we examined the flexibility of memory retrieval in an associative task taxing memories of different strength, assumed to differentially engage episodic and semantic memory. Healthy volunteers were pre-trained on a set of 36 face-name pairs over a 6-week period. Another set of 36 items was shown only once during the same time period. About 3 months after the training period all items were presented in a randomly intermixed order in an event-related fMRI study of face-name memory. Once presented items differentially activated anterior cingulate cortex and a right prefrontal region that previously have been associated with episodic retrieval mode. High-familiar items were associated with stronger activation of posterior cortices and a left frontal region. These findings fit a model of memory retrieval by which early processes determine, on a trial-by-trial basis, if the task can be solved by the default semantic system. If not, there is a dynamic shift to cognitive control processes that guide retrieval from episodic memory.     

Procaine impairs learning and memory consolidation in the honeybee

In vertebrates local anaesthetics lead to various learning deficits, depending on the site and time of injection. In this study we show the effects of the local anaesthetic procaine on learning and memory in an invertebrate, the honeybee. Reversible blocking of neuronal processes leads to different memory deficits depending on the time window during which the local anaesthesia is in effect.     

The behavioral neurobiology of learning and memory: A conceptual reorientation

Research on the neurobiology of learning and memory has been guided by two major theories: (i) memory as a psychological process and (ii) memory as a change in synaptic neural connectivity. It is not widely recognised that not only are these theories different but, moreover, they are fundamentally incompatible. Confusion concerning basic concepts in the learning and memory field in mammals has lead to the creation of an extensive but often inconclusive experimental literature. However, one important conclusion suggested by recent work in this field is that experience-dependent changes in neural connectivity occur in many different brain systems. Particular brain structures, such as the hippocampus, do not play any uniquely important role in experience-dependent behavior. Research in learning and memory can be best pursued on the basis of biological studies of animal behavior and a cellular approach to brain function.     

Glutamate receptor function in learning and memory

The contribution of glutamate to synaptic transmission, plasticity and development is well established; current evidence is based on diverse approaches to decipher function and malfunction of this principal transmitter. With respect to learning and memory, we are now able to identify more specifically the role played by the three main glutamate receptor classes in learning and memory: centre stage is clearly the NMDA receptor, with overwhelming evidence proving its involvement in the actual learning process (encoding), throughout the animal kingdom. This is discussed with respect to many different types of learning. Evidence for the contribution of the AMPA receptors (AMPARs) is less clear-cut due to the general problem of specificity: block of AMPARs will shutdown neuronal communication, and this will affect various components essential for learning. Therefore, the role of AMPARs cannot be established in isolation. Problems of interpretation are outlined and a specific involvement of AMPARs in the regulation of neuronal excitation related to learning is proposed. Metabotropic glutamate receptors (mGluRs) may contribute very little to the actual acquisition of new information. However, memory formation appears to require mGluRs, through the modulation of consolidation and/or recall. Overall, mGluR functions seem variable and dependent on brain structure and learning task.     

Epigenetic mechanisms regulating learning and long-term memory

A balance between rapid, short lived, neuronal responses and prolonged ones fulfill the biochemical and cellular requirements for creating a molecular memory. I provide an overview of epigenetic mechanisms in the brain and discuss their impact on synaptic plasticity, cognitive functions, and discuss a recent example of how they can contribute to neurodegeneration and the cognitive decline associated with Alzheimer's disease.