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21.
异丙酚对神经元缺氧损伤的保护及其作用机制 总被引:8,自引:2,他引:8
目的 研究异丙酚对离体大鼠海马神经元缺氧损伤的保护作用及其机制。方法 以原代培养的大鼠海马神经元作为研究对象 ,建立缺氧、H2 O2 和谷氨酸损伤模型 ,用MTT法测定神经元存活率。采用激光扫描共聚焦显微镜动态监测缺氧前后 ,单个海马神经元内Ca2 + 浓度和线粒体膜电位 (△Ψm)的变化。用电子自旋共振技术测定异丙酚对羟基自由基和超氧阴离子自由基的清除作用。结果 6~ 4 8mg·L-1浓度的异丙酚可明显降低神经元缺氧损伤时的细胞死亡率 (P <0 0 1) ,作用程度均呈剂量相关 (r =0 89,P <0 0 5 ) ;2 4~ 4 8mg·L-1浓度的异丙酚可明显降低H2 O2 损伤时的细胞死亡率 (P <0 0 1) ;12~ 4 8mg·L-1浓度的异丙酚可明显降低谷氨酸损伤时的细胞死亡率 (P <0 0 1)。 3~ 4 8mg·L-1异丙酚对缺氧诱发的细胞内钙离子超载有抑制作用(P <0 0 5 ) ;12、4 8mg·L-1异丙酚能减缓缺氧引起的△Ψm降低 (P <0 0 1)。 12、4 8mg·L-1异丙酚对羟基自由基的清除率分别为 17 1%和 2 1 1% ,但对超氧阴离子自由基无清除作用。结论 异丙酚对离体培养的大鼠海马神经元缺氧性损伤具有保护作用 ,其作用机制部分与异丙酚抑制缺氧引起的 [Ca2 + ]i 异常升高、抑制线粒体膜电位的下降和清除羟基自由基有关 相似文献
22.
Nerve growth factor (NGF) plays a crucial role in synaptic plasticity during brain development and adulthood by activating a dual receptor system composed of TrkA and p75 (p75NTR) receptors. Exogenous NGF modulates the expression of both receptors. Little is known about the ability of endogenous NGF to regulate the expression of these receptors in basal forebrain cholinergic terminals. The ability of glucocorticoids to increase NGF expression in the hippocampus prompted us to investigate whether the synthetic glucocorticoid dexamethasone (DEX) increases TrkA and p75NTR expression in NGF-target cholinergic neurons in developing rats. We first examined the effect of DEX on NGF mRNA by in situ hybridization. DEX given systemically (0.5 mg/kg, sc) for 1 week to 7-day-old rats elicited an increase in NGF mRNA levels in the dentate gyrus of the hippocampus and superficial layers II and III of the cerebral cortex. Immunohistochemical analysis of p75NTR and TrkA levels revealed a dramatic increase in p75NTR immunoreactivity (IR) in both basal forebrain and hippocampus and TrkA IR in the hippocampus. Interestingly, in DEX-treated rats more axonal terminals were immunopositive for p75NTR in the hippocampus and cortex, suggesting an increase in p75NTR IR in cell bodies as well as in terminals. Our data indicate that the endogenously produced NGF elicits biological changes similar to those of the exogenously delivered NGF. We suggest that glucocorticoids might regulate and coordinate cholinergic neuronal maturation by increasing the biosynthesis of NGF. 相似文献
23.
The role of calcium and protein kinases in rhythmic activity induced by muscarinic receptor activation in the CA1 area in rat hippocampal slices was investigated. Extracellular recording showed that carbachol (20 microM) induced synchronized field potential activity with a dominant frequency of 7.39+/-0.68 Hz. Pretreatment with the membrane permeable Ca(2+) chelator BAPTA-AM (50 microM) or with thapsigargin (1 microM), a compound which depletes intracellular calcium stores, reduced the dominant power of carbachol-induced theta-like activity by 83% and 78%, respectively. Inhibition of calmodulin-dependent protein kinase II (CaMKII) by the cell permeable inhibitor KN-93 (10 microM) reduced the power of carbachol-induced theta-like activity by 80%. In contrast the protein kinase C (PKC) inhibitor calphostin C did not significantly (P>0.05) affect the effect of carbachol. Whole-cell recording indicated that KN-93 also blocked carbachol-induced suppression of slow I(AHP) and strongly inhibited the carbachol-induced plateau potential. Our data suggest that activation of CaMKII by carbachol is crucial for local theta-like activity in the CA1 area of the rat hippocampus in vitro. Furthermore, involvement of CaMKII in carbachol-induced suppression of the slow I(AHP) and the induction of plateau potentials could play a role in the induction of theta-like rhythmic activity by carbachol. 相似文献
24.
Fukutani Y Cairns NJ Shiozawa M Sasaki K Sudo S Isaki K Lantos PL 《Psychiatry and clinical neurosciences》2000,54(5):523-529
To explore more fully the relationship between neuronal death and neurofibrillary degeneration, unaffected neurons, intracellular neurofibrillary tangles (i-NFT) and extracellular NFT (e-NFT) in 22 patients with late-onset sporadic Alzheimer's disease (AD) were morphometrically evaluated in eight subdivisions of the hippocampal cortex, using the Gallyas hematoxylin-eosin stain. The subdivisions examined included CA4, CA3, CA2, CA1 (CA: cornu ammonis), prosubiculum (PRO), subiculum and presubiculum (PRE), parasubiculum (PARA) and the entorhinal cortex (ENT). The unaffected neuron density was significantly lower and both i-NFT and e-NFT densities were significantly higher in subdivisions other than CA4 and CA3 in AD patients compared with those in the aged controls. Unaffected neuron density was significantly, inversely correlated with e-NFT density and with total NFT density in all subdivisions except for PRE in AD patients. Especially in CA2, CA1, PRO and ENT, there were strong correlations between the neuron density and these NFT densities. Both unaffected neuron and e-NFT densities in CA1 and ENT were significantly correlated with the disease duration. The i/e-NFT ratio, an index of the degree and/or rate of progress of neuronal death via neurofibrillary degeneration, showed the lowest value in ENT in AD patients. The findings suggest that neuronal death via neurofibrillary degeneration starts earliest and/or most rapidly progresses in ENT. Furthermore, the i/e-NFT ratios in both ENT and CA1 were significantly correlated with the disease duration, suggesting that the neuronal death pattern in the two subdivisions parallels disease progression. 相似文献
25.
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 总被引:7,自引:1,他引:7
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。 相似文献
26.
目的研究加味五子衍宗方及其总多糖、总黄酮含药脑脊液对β淀粉样蛋白诱导的原代大鼠海马神经元损伤的保护作用。方法体外原代培养大鼠胎鼠海马神经元,并将加味五子衍宗方的提取物(总方、总多糖、总黄酮)对大鼠进行灌胃给药,然后抽取含药脑脊液,将含药脑脊液与20μmol/L的Aβ25-35共同作用海马神经元24h后,分别检测正常对照组、Aβ25-35损伤组、空白脑脊液保护组、加味五子衍宗方含药脑脊液(总方、总多糖、总黄酮)保护组的海马神经元活力、凋亡率以及凋亡相关蛋白(caspase-3,PARP,Bcl-2,Bcl-XL,JNK1/2,p38MAPK)的变化情况。结果加味五子衍宗方不同提取物(总方、总多糖、总黄酮)的含药脑脊液对Aβ25-35所诱导的海马神经元毒性均有保护作用,且总黄酮、总多糖含药脑脊液的保护作用明显高于总方含药脑脊液(P0.05或P0.01),但是加味五子衍宗方不同组分(总方、总多糖、总黄酮)的含药脑脊液对凋亡相关蛋白的调控机制并不一致。结论加味五子衍宗方中的部分黄酮类和多糖类成分可以透过血脑屏障并进入脑脊液,同时这些成分对β淀粉样蛋白所致的神经损伤有一定的保护作用。 相似文献
27.
目的观察具有益气补肾活血化痰作用的中药提取物健脑安对血管性疾呆(VaD)大鼠海马区表达升高的白细胞介素1β(interleukin-1,IL-1β)、促肾上腺皮质激素释放因子(corticotropin-releasing factor,CRF)的影响。方法对 Koizumi 和 Nagasawa 法加以改进,采用同侧颈总动脉永久结扎线栓法制备大脑中动脉梗塞(MCAO)大鼠模型,2h 后实现大脑中动脉再灌。动物分成中药健脑安大(19.34g 生药/ml)、中(9.67g 生药/ml)、小(4.83g 生药/ml)剂量组、白细胞介素1受体拮抗剂(IL-1ra)对照组、模型组和假手术组。中药干浸膏用0.5%羧甲基纤维素(CMC)配咸水溶液,每100g 大鼠给中药溶液0.7ml;IL-1ra 对照组大鼠在缺血前30min和缺血后10min 左侧脑室内分别注射人重组 IL-1ra 10μg;3个中药剂量组、假手术组、模型组分别于造模7天前开始灌胃中药及清洁水,分别按照缺血再灌后不同时间点(2、3、4、12h 和7天)取材。应用免疫组化方法标记实验各组大鼠脑海马区组织中 IL-1β和 CRF 蛋白阳性神经元的数量。结果... 相似文献
28.
Fang Huang Nittaya Marungruang Olha Kostiuchenko Nadiia Kravchenko Stephen Burleigh Olena Prykhodko Frida Fk Hllenius Lovisa Heyman-Lindn 《Nutrients》2022,14(13)
High-fat diets are associated with neuronal and memory dysfunction. Berries may be useful in improving age-related memory deficits in humans, as well as in mice receiving high-fat diets. Emerging research has also demonstrated that brain health and cognitive function may be related to the dynamic changes in the gut microbiota. In this study, the impact of Nordic berries on the brain and the gut microbiota was investigated in middle-aged C57BL/6J mice. The mice were fed high-fat diets (60%E fat) supplemented with freeze-dried powder (6% dwb) of bilberry, lingonberry, cloudberry, blueberry, blackcurrant, and sea buckthorn for 4 months. The results suggest that supplementation with bilberry, blackcurrant, blueberry, lingonberry, and (to some extent) cloudberry has beneficial effects on spatial cognition, as seen by the enhanced performance following the T-maze alternation test, as well as a greater proportion of DCX-expressing cells with prolongation in hippocampus. Furthermore, the proportion of the mucosa-associated symbiotic bacteria Akkermansia muciniphila increased by 4–14 times in the cecal microbiota of mice fed diets supplemented with lingonberry, bilberry, sea buckthorn, and blueberry. These findings demonstrate the potential of Nordic berries to preserve memory and cognitive function, and to induce alterations of the gut microbiota composition. 相似文献
29.
目的:观察苯丙胺对大鼠海马结构内星形胶质细胞的影响。方法:SD大鼠130只按随机数字表法分为正常组43只,生理盐水组43只和苯丙胺组44只。苯丙胺组给予大鼠每天肌肉注射O.5mg/kg剂量的苯丙胺1次;生理盐水组注射等体积的生理盐水,正常组不予处理。用水迷宫训练苯丙胺组和生理盐水组大鼠建立空间辨别性学习记忆模型,用免疫组织化学方法和Western免疫印迹定性和定量胶质原纤维酸性蛋白质(GFAP)的表达。结果:苯丙胺组和生理盐水组海马各亚区的GFAP免疫阳性产物的灰度值与正常组相比明显降低,差异有显著性(P〈0.05),其中苯丙胺组的灰度值最低;苯丙胺组大鼠海马结构内GFAP蛋白表达量比其他两组明显增加(P〈0.05),苯丙胺组内海马结构GFAP蛋白表达量在模型42d内,随时间增加而增加。结论:在本实验条件下,苯丙胺可引起大鼠海马结构GFAP表达显著升高。 相似文献
30.