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1.
新生小鼠脑缺氧缺血性脑病模型的制作   总被引:5,自引:0,他引:5  
目的建立新生C57BL/6小鼠缺氧缺血性脑病(HIE)模型,并讨论模型制作中的相关问题。方法采用健康7日龄C57BL/6新生小鼠,结扎后剪断右侧颈总动脉,置于37℃、8%低氧浓度环境下,分别于30min、60min、90min、120min取出,并于不同时间处死小鼠,观察脑组织病理改变,并进行行为学检测。结果(1)HIE模型组小鼠寻找目标所需时间和路径远长于正常组小鼠,且其与正常组间评分有统计学意义(P<0.05)。(2)随着缺氧时间的延长,HIE小鼠12h内死亡率逐渐增高,当缺氧达90min时,死亡率为10%,缺氧120min时,死亡率高达83%。(3)HIE模型组甲苯胺蓝染色见神经细胞核固缩,着色加深,胞浆Nissl小体明显减少;HE染色可见右侧大脑皮层、海马等区域神经细胞明显减少,尤以海马区为明显,神经细胞变性坏死、胶质细胞反应性增生,形成胶质细胞结节。(4)病理改变与缺氧时间、缺血缺氧(HI)损伤后时间点有关。结论本方法制作新生C57BL/6小鼠HIE模型获得成功。该模型具有进一步推广意义。  相似文献
2.
经典的小鼠大脑中动脉闭塞再灌注模型的建立和评价   总被引:4,自引:1,他引:3  
目的:建立经典的小鼠大脑中动脉闭塞再灌注模型。方法:以头端涂硅胶的尼龙线自左颈外动脉向颈内动脉插入至大脑中动脉起始部,阻断血流2h后拔出线栓再灌注。通过神经功能评分和氯化三苯基四氮唑(tetrazoliumchloride,TTC)染色对模型进行评价。结果:小鼠缺血2h后,出现自主活动时向右旋转等功能障碍表现,TTC染色显示出梗死范围。再灌后22hTTC改变加重,神经病学评分同前。结论:该模型可以控制缺血和再灌注时间,是研究脑栓塞病理生理等的经典动物模型。  相似文献
3.
目的探讨盐酸多奈哌齐对血管性痴呆(VD)模型小鼠海马神经元中细胞外信号调节激酶(ERK)表达的影响。方法采用双侧颈总动脉反复缺血-再灌注法制备小鼠VD模型。将小鼠随机分为假手术组、模型组及盐酸多奈哌齐治疗组,药物组给予盐酸多奈哌齐灌胃治疗。术后第29、30天,采用跳台试验和水迷宫试验对各组小鼠进行行为学成绩测试,采用免疫组化法观察各组小鼠海马神经元ERK表达的变化。结果盐酸多奈哌齐可明显改善VD模型小鼠学习、记忆成绩(P<0.05)。模型组小鼠海马CA1区ERK1、ERK2表达及海马CA3区p-ERK表达较假手术组及治疗组减少(均P<0.05)。结论盐酸多奈哌齐通过增加乙酰胆碱含量,后者作用于毒蕈碱乙酰胆碱受体(M受体)激活ERK,从而有助于改善学习和记忆功能。海马神经元内ERK的表达减少可能参与了VD的发病机制。  相似文献
4.
远交系小鼠作为轻度认识障碍动物模型的可行性   总被引:2,自引:0,他引:2       下载免费PDF全文
轻度认知障碍(MCI)患者常进展为阿尔茨海默病,其最早症状之一是空间学习记忆的减退。终止或延缓这一顽固性疾病造成损害的最佳策略是使用该病变调剂或针对这些临床前症状的人群给予认知促进剂。但是迄今为止,尚缺少MCI的动物模型以帮助评估治疗策略的有效性。因此,本研究的目的是获得MCI的小鼠模型。分别对两个年龄组的小鼠(昆明5月和12.5月和ICR 7月和12月)进行了研究。 Morris水迷宫和六臂水迷宫被用来评估是否中年小鼠会表现出空间学习和记忆障碍。结果表明,与各自的年轻小鼠相比,中年鼠在这两种方法上存在明显空间记忆受损,在六臂水迷宫仅出现轻度空间学习的损害。因此,这些远交系鼠(昆明和ICR小鼠)可作为MCI的自然动物模型,特别是针对记忆障碍的研究。  相似文献
5.
8-oxo-G在快速老化小鼠SAMP8海马中表达的增龄性变化研究   总被引:2,自引:0,他引:2  
目的观察8-氧鸟嘌呤核苷(8-oxo-G)在SAMP8品系快速老化小鼠海马不同区域的表达,以探讨其与SAMP8小鼠增龄性变化的关系。方法选用1、4、8、12月龄的快速老化小鼠SAMP8以及同龄抗快速老化小鼠SAMR1(对照组),每组各6只,采用免疫组化方法检测小鼠海马不同区域8-oxo-G的表达。结果8-oxo-G主要在SAM小鼠海马神经元胞浆内表达。对照组SAMR1 1月龄小鼠海马CA1和CA3区8-oxo-G表达显著高于其他月龄组(P<0.05),4、8、12月龄小鼠间其表达差异无统计学意义(P>0.05);SAMP8 12月龄小鼠海马8-oxo-G的表达显著高于1、4、8月龄组(P<0.05);SAMP8和SAMR1小鼠之间比较,1、4月龄间差异无统计学意义(P>0.05),8、12月龄间差异有统计学意义(P<0.05)。结论SAMP8小鼠海马8-oxo-G的表达除1月龄外随月龄增加而增加,提示8-oxo-G的表达增加与SAMP8小鼠的快速老化相关,有可能为增龄,甚至AD的生物学标志。  相似文献
6.
BACKGROUND: Substantia nigra is deep in position and limited in range, the glial cell line-derived neurotrophic factor (GDNF) injection directly into substantia nigra has relatively greater damages with higher difficulty. GDNF injection into striatum, the target area of dopaminergic neuron, may protect the dopaminergic neurons in the compact part of substantia nigra through retrograde transport. OBJECTIVE: To investigate the protective effect of intrastriatal GDNF on dopaminergic neurons in the substantia nigra of mice with Parkinson disease (PD), and analyze the action pathway. DESIGN: A controlled observation. SETTING: Neurobiological Laboratory of Xuzhou Medical College. MATERIALS: Twenty-four male Kunming mice of 7–8 weeks old were used. GDNF, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were purchased from Sigma Company (USA); LEICAQWin image processing and analytical system. METHODS: The experiments were carried out in the Neurobiological Laboratory of Xuzhou Medical College from September 2005 to October 2006. The PD models were established in adult KunMing mice by intraperitoneal injection of MPTP. The model mice were were randomly divided into four groups with 6 mice in each group: GDNF 4-day group, phosphate buffer solution (PSB) 4-day group, GDNF 6-day group and PSB 6-day group. Mice in the GDNF 4 and 6-day groups were administrated with 1 μL GDNF solution (20 μg/L, dispensed with 0.01 mol/L PBS) injected into right striatum at 4 and 6 days after model establishment. Mice in the PSB 4 and 6-day groups were administrated with 0.01 mol/L PBS of the same volume to the same injection at corresponding time points. ② On the 12th day after model establishment, the midbrain tissue section of each mice was divided into 3 areas from rostral to caudal sides. The positive neurons of tyroxine hydroxylase (TH) and calcium binding protein (CB) with obvious nucleolus and clear outline were randomly selected for the measurement, and the number of positive neurons in unit area was counted. MAIN OUTCOME MEASURES: Number of positive neurons of TH and CB in midbrain substantia nigra of mice in each group. RESULTS: All the 24 mice were involved in the analysis of results. The numbers of TH+ and CB+ neurons in the GDNF 4-day group (54.33±6.92, 46.33±5.54) were obviously more than those in the PBS 4-day group (27.67±5.01, 21.50±5.96, P < 0.01). The numbers of TH+ and CB+ neurons in the GDNF 6-day group (75.67±5.39, 69.67±8.69) were obviously more than those in the PBS 6-day group (27.17±4.50, 21.33±5.72, P < 0.01) and those in the GDNF 4-day group (P < 0.01). CONCLUSION: Intrastriatal GDNF can protect dopaminergic neurons in substantia nigra of PD mice, and it may be related to the increase of CB expression.  相似文献
7.
BACKGROUND: It has been confirmed that brain-derived neurotrophic factor (BDNF) can promote the proliferation of neural stem cells (NSCs) and protect neuron-like cells in vitro. However, its effect on endogenous NSCs in vivo is still unclear. OBJECTIVE: To evaluate whether BDNF can induce the endogenous NSCs to proliferate and differentiate into the neurons in the mice model of cerebral infarction. DESIGN: A synchronal controlled observation. SETTINGS: Department of Neurology, Microbiology Division of the Department of Laboratory, Tianjin First Central Hospital; Howard Florey Institute, Medical College, the University of Melbourne. MATERIALS: Twenty-four pure breed C57BL/6J mice at the age of 10 weeks old (12 males and 12 females) were divided into saline control group and BDNF-treated group, 6 males and 6 females in each group. METHODS: The experiments were performed at the University of Melbourne from July 2004 to February 2005. ① The left middle cerebral artery (MCA) was ligated in both groups to establish models of cerebral infarction and the Matsushita measuring method was used to monitor the blood flow of the lesioned region supplied by MCA. 75% reduction of blood flow should be reached in the lesioned region. ② At 24 hours after infarction, mice in the BDNF-treated group were administrated with BDNF, which was slowly delivered using an ALZET osmium pump design. BDNF was dissolved in saline at the dosage of 500 mg/kg and injected into the pump, which could release the solution consistently in the following 28 days. The mice in the saline control group accepted the same volume of saline at 24 hours after infarction. ③ The Rotarod function test began at 1 week preoperatively, the time stayed on Rotarod was recorded. The mice were tested once a day till the end of the experiment. At 4 weeks post cerebral infarction, double labeling of Nestin and GFAP, BIH tubulin and CNPase immunostaining was performed to observe the differentiation directions of the re-expressed endogenous NSCs, and the percentages of the cells differentiated into astrocytes, neurons and oligodendrocytes were calculated. MAIN OUTCOME MEASURES: ① The differentiation directions of the re-expressed endogenous NSCs, and the percentage of the cells differentiated into astrocytes, neurons and oligodendrocytes.② Comparison of motor function between the two groups. RESULTS: All the 24 pure C57BL/6J mice were involved in the analysis of results. ①Positively expressed endogenous NSCs appeared in the mice of both groups, and they mainly distributed around the focus of lesion, as well as the contralateral side. The expressed cells in the BDNF-treated group were obviously more than those in the saline control group. ②Activations of endogenous NSCs: At 4 weeks after infarction, re-expressions of endogenous NSCs appeared in both groups. The number of the re-expressed cells in the BDNF-treated group was about 4.2 times higher than that in the saline control group. The percentage of the cells differentiated into neurons in the BDNF-treated group was significantly higher than that in the saline control group (36%, 15%), the percentage of the cells differentiated into astrocytes was lower than that in the saline control group (54%, 77%), whereas the percentage of the cells differentiated into oligodendrocytes was similar to that in the saline control group (10%, 8%). ③ Results of motor functional test: Compared with before cerebral infarction, the mice in both groups manifested as obvious decrease in motor function at 1 week after infarction, whereas the recovery of motor function in the BDNF-treated group was significantly superior to that in the saline control group at 2, 3 and 4 weeks (P 〈 0.01). CONCLUSION: BDNF can promote the proliferation of endogenous NSCs in the brain of mice with cerebral infarction, it can decrease the differentiation rate of astrocytes, and increase the differentiation rate of neurons. BDNF has small influence on the differentiation of endogenous NSCs into oligodendrocytes, which was not benefit for the recovery of neural axon. Endogenous NSCs may improve the motor function of mice through the above pathways.  相似文献
8.
不同培养条件神经干细胞早期分化特征观察   总被引:1,自引:1,他引:0  
目的 探讨不同培养条件对小鼠神经干细胞早期分化形态学的影响.方法 用无血清条件培养基、5%胎牛血清+条件培养基培养与单细胞克隆技术对小鼠胚胎脑组织进行分离、培养及诱导分化,在光学显微镜下观察培养细胞分化2 w内形态学变化,对培养细胞用免疫组织化学法鉴定.结果 无血清培养瓶内细胞分化早期呈极性排列,而5%胎牛血清+条件培养基培养组,克隆球间存在着广泛的网络结构,且单一神经干细胞核分裂旺盛,克隆球数目多且比较大.结论 小鼠神经干细胞间早期存在某种依赖关系,在适当的微环境中,神经球之间可能存在信息传递.  相似文献
9.
煮沸裂解法快速提取Tg2576小鼠DNA   总被引:1,自引:0,他引:1  
目的建立Tg2576小鼠DNA快速简便高效的提取方法。方法借鉴煮沸裂解法制备质粒DNA方法,改进后用于提取Tg2576小鼠DNA,比较酚/氯仿法和煮沸裂解法两种提取DNA的方法。结果在小鼠鉴定过程中,使用酚/氯仿法和煮沸裂解法提取DNA均能取得满意的结果;但前者操作繁琐,至少需2d完成,而后者操作步骤大大简化,可在1d内完成,且提取所用试剂毒性小、成本低。结论煮沸裂解法提取DNA灵敏度高、耗时短、操作简便,值得在Tg2576小鼠基因型鉴定中使用,也可以在其他转基因动物鉴定实验中推广。  相似文献
10.
目的 探讨常压高氧(40%O_2,60%空气)处理淀粉样蛋白前体/早老素1(APP/PS1)双重转基因小鼠是否发挥神经保护作用.方法 对APP/PS1双重转基因阿尔茨海默病(AD)模型种鼠交配后产下的子代小鼠进行基因分型,待子代达10周龄时,取双重转基因小鼠40只,随机分成A、B、C、D 4组,每组10只,A、B 2组小鼠喂养于常压高氧中8 h/d,A组持续4周,B组持续8周;C、D组喂养于空气中4或8周,分别作为A、B组的对照.高氧处理后采用免疫组织化学、Thioflavin S染色检测小鼠脑组织形态学的变化,Western blot检测APP代谢过程中相关蛋白的表达变化,ELISA定量检测小鼠脑内β-淀粉样蛋白(Aβ)水平的变化.结果 免疫组织化学和Thioflavin S染色均显示,与对照组相比,高氧处理组小鼠皮质和海马内老年斑数量明显减少,B组比A组减少更显著.高氧处理组小鼠脑内C_(99)、C_(83)水平显著高于对照组,Aβ水平明显低于对照组,但各组小鼠脑内全长APP及β位淀粉样前体蛋白裂解酶1(BACE1)蛋白水平无明显改变.ELISA结果提示,B组小鼠海马和皮质内Aβ_(40)[(783.6±97.2)pg/ml]和Aβ_(42)[(175.3±17.1)ps/ml]含量明显低于对照组Aβ_(40)[(1251.6±42.3)pg/ml,t=9.36,P<0.01]和Aβ_(42)[(286.8±13.0)pg/ml,t=13.7,P<0.01]的含量.结论 常压高氧处理能显著减少AD模型小鼠脑内Aβ的产生、沉积及老年斑的形成;这种改变可能通过减少Aβ产生或加速Aβ清除实现.  相似文献
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