帕金森病的神经保护治疗

帕金森病是一种常见的中枢神经系统变性疾病,其神经退变进行性加重,会导致患者严重残疾,寿命缩短,目前尚无有效的预防和根治措施.大量研究表明,帕金森病的发病机制涉及到线粒体功能和氧化应激,免疫反应,营养因子缺乏,细胞凋亡,蛋白质异常表达等.神经保护治疗能够延缓或终止帕金森病的进展,预防残疾的进一步加重.     

The inflammatory event of birth: How oxytocin signaling may guide the development of the brain and gastrointestinal system

The role of oxytocin (OT) as a neuropeptide that modulates social behavior has been extensively studied and reviewed, but beyond these functions, OT’s adaptive functions at birth are quite numerous, as OT coordinates many physiological processes in the mother and fetus to ensure a successful delivery. In this review we explore in detail the potential adaptive roles of oxytocin as an anti-inflammatory, protective molecule at birth for the developing fetal brain and gastrointestinal system based on evidence that birth is a potent inflammatory/immune event. We discuss data with relevance for a number of neurodevelopmental disorders, as well as the emerging role of the gut-brain axis for health and disease. Finally, we discuss the potential relevance of sex differences in OT signaling present at birth in the increased male vulnerability to neurodevelopmental disabilities.     

Raloxifene activates G protein-coupled estrogen receptor 1/Akt signaling to protect dopamine neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice

Raloxifene, used in the clinic, is reported to protect brain dopaminergic neurons in mice. Raloxifene was shown to mediate an effect through the G protein-coupled estrogen receptor 1 (GPER1). We investigated if raloxifene neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated male mice is mediated through GPER1 by using its antagonist G15. Striatal concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid to dopamine ratio as well as dopamine transporter and vesicular monoamine transporter 2 showed that raloxifene neuroprotection of dopaminergic neurons was blocked by G15. Protection by raloxifene was accompanied by activation of striatal Akt signaling (but not ERK1/2 signaling) and increased Bcl-2 and brain-derived neurotrophic factor levels; these effects were abolished by coadministration with G15. The effect of raloxifene was not mediated through increased levels of 17β-estradiol. MPTP mice had decreased plasma testosterone, dihydrotestosterone, and 3β-diol levels; this was prevented in raloxifene–treated MPTP mice. Our results suggest that raloxifene acted through GPER1 to mediate Akt activation, increase Bcl-2 and brain-derived neurotrophic factor levels, and protection of dopaminergic neurons and plasma androgens.     

沉默信息调节蛋白1在缺血性脑损伤中的神经保护作用

近年来，沉默信息调节蛋白1（silent information regulator protein 1，SIRT1）作为依赖NAD+ 的组蛋白去乙酰化酶被广泛地研究。SIRT1存在于机体各组织细胞中，通过去乙酰化修饰，调节细胞 的多种生理过程，在能量守恒、细胞氧化、衰老及凋亡等方面发挥重要作用。目前认为，SIRT1在缺血 性脑损伤中起到神经保护作用，可能通过调控细胞能量代谢，抗炎性反应、抗细胞凋亡等方面发挥 作用。本文主要综述了SIRT1在缺血性脑损伤中的神经保护作用。     

Neuroprotective effects of the catalytic subunit of telomerase: A potential therapeutic target in the central nervous system

Senescence plays an important role in neurodegenerative diseases and involves key molecular changes induced by several mechanisms such as oxidative stress, telomere shortening and DNA damage. Potential therapeutic strategies directed to counteract these molecular changes are of great interest for the prevention of the neurodegenerative process. Telomerase is a ribonucleoprotein composed of a catalytic subunit (TERT) and a RNA subunit (TERC). It is known that the telomerase is involved in the maintenance of telomere length and is a highly expressed protein in embryonic stages and decreases in adult cells. In the last decade, a growing number of studies have shown that TERT has neuroprotective effects in cellular and animal models after a brain injury. Significantly, differences in TERT expression between controls and patients with major depressive disorder have been observed. More recently, TERT has been associated with the decrease in reactive oxygen species and DNA protection in mitochondria of neurons. In this review, we highlight the role of TERT in some neurodegenerative disorders and discuss some studies focusing on this protein as a potential target for neuroprotective therapies.     

颈部血管低温液体输注的研究进展

治疗性低温是一种切实有效的脑保护措施,可以通过降低代谢率、减轻脑水肿、阻断细胞凋亡、降低细胞内钙离子内流、抑制炎症反应以及谷氨酸的释放等多种机制起到明确的神经保护作用[1-4].目前已在临床上使用于心脏骤停导致的缺血缺氧性脑病、缺血性中风和严重颅脑外伤等疾病的治疗中.全身低温是目前最常用的低温方式,但实施过程中伴随的感染、凝血功能障碍和心律失常等并发症严重影响了其治疗效果f5].选择性脑降温(selective brain cooling,SBC)是指选择性降低大脑温度而不降低全身体温的一种降温方法.     

七氟烷对发育中大脑是保护还是损害

背景 七氟烷是一种优良的新型吸入麻醉剂,具有血/气分配系数低,麻醉诱导时间短,麻醉深度易于控制,清醒速度快,肝肾功能影响小,血流动力学稳定等特点.而其所具有的芳香味,使七氟烷在小儿麻醉中更具优势.了解七氟烷对发育中大脑的影响可使麻醉医师在临床应用时扬长避短. 目的 对以往文献进行回顾并综合目前最新研究进展,深入分析七氟烷对发育中大脑的影响. 内容 已有大量关于七氟烷对发育中大脑影响的研究,由于临床试验的局限性,大部分研究都在动物模型上实施,七氟烷对发育中大脑是具有保护作用抑或是损害,其机制是什么,不同的研究者试验结论不一致甚至相悖.趋势 目前关于吸入麻醉药的麻醉作用机制和神经保护、神经毒性作用机制已经深入到分子水平.由于大脑内存在多种信号通路、离子通道以及神经递质,使得七氟烷对大脑影响的机制变得复杂,进行更深入的研究迫在眉睫.