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121.
目的 探讨快速衰老小鼠(SAMP8)中Klotho低表达对β淀粉样肽(Aβ)清除的影响.方法 采用Y迷宫和跳台实验评测12月龄SAMP8小鼠和抗衰老系列小鼠(SAMR1)的学习和空间记忆能力;免疫组化检测小鼠脑中Aβ1-42、同种异体移植炎性因子-1(AIF1)、胶质纤维酸性蛋白(GFAP)和Klotho的变化;蛋白免疫印迹法检测低密度脂蛋白受体相关蛋白(LRP-1)、晚期糖基化末端产物(RAGE)的蛋白表达.结果 与SAMR1小鼠相比,SAMP8小鼠的学习、记忆功能明显下降,脑内Aβ1-42、AIF1、GFAP和RAGE的表达显著增加,Klotho和LRP-1的表达明显降低.结论 SAMP8小鼠中Klotho表达的降低可能导致LRP-1降低和RAGE增加,从而增加Aβ在脑内沉积. 相似文献
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中枢神经炎症在多种中枢神经系统疾病的病理发展过程中至关重要,一定程度的神经炎症可以促进脑损伤后的神经修复,但过度的病理性神经炎症则是导致继发性脑损伤,影响神经功能恢复的重要原因。临床及基础研究表明,艾灸可调节脑损伤后脑内胶质细胞极化状态,调控炎症介质及相关通路表达,减少炎症小体的生成和抑制细胞凋亡,还可减轻血脑屏障的通透性,这些可能是艾灸能够在多种脑部疾病中发挥抗炎作用的共同机制所在。因此,通过对艾灸抑制神经炎症的作用途径及机制进行总结分析,可更好地帮助理解艾灸的中枢效应,促进其应用的临床转化。 相似文献
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术后认知功能障碍(POCD)是手术和麻醉后的常见并发症,老年患者预后较差。POCD表现为注意力、意识、知觉和判断力下降,并时常伴随情绪和人格行为的异常改变,对患者和其家庭有较大的社会和经济影响。POCD相关机制包括中枢神经炎症和外周炎性因子的共同作用,其中神经炎症在POCD的病理生理发展过程中十分重要,然而神经炎症参与POCD发生与发展的机制尚不明确。本文章就神经炎症及其相关研究机制与POCD的关系做一综述,以期为探究POCD的发病机制和寻找新的潜在靶点提供新思路。 相似文献
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围术期神经认知障碍(PND)是一种常见的围术期神经系统并发症,表现为注意力不集中,学习能力下降和记忆受损,可影响患者术后短期功能恢复及预后,延长患者的住院时间。目前PND的发生机制仍存在争议。补体系统是一种生物级联反应体系,已被证实在多种神经退行性疾病的发生发展过程中起着重要作用。麻醉及手术刺激可激活中枢神经系统中的补体系统,影响神经炎症反应、突触功能、血脑屏障、血脑脊液屏障,引起或加重PND。本文章就补体系统对围术期神经认知功能的影响做一系统综述,以期为PND的潜在药物靶点和治疗提供参考。 相似文献
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Steven Vetel Sophie Srrire Johnny Vercouillie Jackie Vergote Gabrielle Chicheri Jean‐Bernard Deloye Frdric Doll Sylvie Bodard Claire Tronel Lydie Nadal‐Desbarats Antoine Lefvre Patrick Emond Sylvie Chalon 《Synapse (New York, N.Y.)》2019,73(3)
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons constituting the nigrostriatal pathway. Neuroinflammation, related to microglial activation, plays an important role in this process. Exploration of animal models of PD using neuroimaging modalities allows to better understand the pathophysiology of the disease. Here, we fully explored a moderate lesion model in the rat in which 6‐hydroxydopamine was unilaterally delivered in three sites along the striatum. The degenerative process was assessed through in vivo Positron Emission Tomography (PET) imaging and in vitro autoradiographic quantitation of the striatal dopamine transporter (DAT) and immunostaining of tyrosine hydroxylase (TH). The microglial activation was studied through in vitro autoradiographic quantitation of the 18 kDa translocator protein (TSPO) in the striatum and CD11b staining in the SN. In addition, a targeted metabolomics exploration was performed in both these structures using mass spectrometry coupled to HPLC. Our results showed a reproducible decrease in the striatal DAT density associated with a reduction in the number of TH‐positive cells in the SN and striatum, reflecting a robust moderate degeneration of nigrostriatal DA neurons. In addition, we observed strong microglia activation in both the striatum and SN ipsilateral to the lesion, highlighting that this moderate degeneration of DA neurons was associated with a marked neuroinflammation. Our metabolomics studies revealed alterations of specific metabolites and metabolic pathways such as carnitine, arginine/proline, and histidine metabolisms. These results bring new insights in the PD mechanism knowledge and new potential targets for future therapeutic strategies. 相似文献
127.
ObjectiveThe average age at the time of spinal cord injury (SCI) has increased to 43 years old. Middle-aged mice (14 months old, MO) exhibit impaired recovery after SCI with age-dependent increases in reactive oxygen species (ROS) production through NADPH oxidase (NOX) along with pro-inflammatory macrophage activation. Despite these aging differences, clinical therapies are being examined in individuals regardless of age based upon preclinical data generated primarily using young animals (∼4 MO). Our objective is to test the extent to which age affects SCI treatment efficacy. Specifically, we hypothesize that the effectiveness of apocynin, a NOX inhibitor, is age-dependent in SCI.MethodsApocynin treatment (5 mg/kg) or vehicle was administered 1 and 6 h after moderate T9 contusion SCI (50kdyn IH) and then daily for 1 week to 4 and 14 MO mice. Locomotor and anatomical recovery was evaluated for 28 days. Monocyte-derived macrophage (MDM) and microglial activation and ROS production were evaluated at 3 and 28 days post-injury.ResultsApocynin improved functional and anatomical recovery in 14 but not 4 MO SCI mice. Apocynin-mediated recovery was coincident with significant reductions in MDM infiltration and MDM-ROS production in 14 MO SCI mice. Importantly, microglial activation was unaffected by treatment.ConclusionThese results indicate that apocynin exhibits age-dependent neuroprotective effects by blocking excessive neuroinflammation through NOX-mediated ROS production in MDMs. Further, these data identify age as a critical regulator for SCI treatment efficacy and indicate that pharmacologically reduced macrophage, but not microglia, activation and ROS production reverses age-associated neurological impairments. 相似文献
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Sta M Sylva-Steenland RM Casula M de Jong JM Troost D Aronica E Baas F 《Neurobiology of disease》2011,42(3):211-220
Increasing evidence suggests a role for the immune system in amyotrophic lateral sclerosis (ALS). To determine the extent of the immune activation in ALS we analyzed the expression and cellular distribution of components of innate and adaptive immunity in spinal cord (SC) and motor cortex (MCx) from patients with rapid and slow sporadic ALS and controls. High levels of mRNA and protein of classical complement pathway, C1q and C4, as well as the downstream complement components C3 and C5b-9 were found in all ALS samples. Furthermore, we found higher numbers of activated microglia, reactive astrocytes, dendritic cells (DCs) and CD8(+) T-cells in ALS than in control tissue. Rapid ALS cases had more dendritic cells than slow ALS cases, whereas slow ALS cases had more activated microglia than rapid cases. Our findings demonstrate a persistent and prominent activation of both innate and adaptive immunity in ALS. We propose a complement-driven immune response which may contribute to the progression of the inflammation and ultimately lead to even more motor neuron injury. 相似文献