BMPs 在中枢神经系统发育和神经保护中的作用

骨形态发生蛋白（Bone morphogenetic proteins,BMPs）是转化生长因子-β（transforming growth factor -β）超家族的成员,现已经发现 BMPs 很多亚型 BMP 分子在神经系统的不同区域呈持续性表达,但是表达在空间和时间具有差异性,提示不同亚型 BMPs 的功能在神经系统也存在差异。本文主要就 BMPs 在中枢神经系统发育中的作用和神经保护功能作一综述。     

帕瑞昔布钠的作用机制及最新进展

帕瑞昔布钠是一种新型的COX-2特异性的抑制剂,现已广泛用于临床上预防和治疗中重度疼痛。但近年来发现,帕瑞昔布钠除了具有镇痛作用外还存在其他的一些非镇痛效应。帕瑞昔布钠具有减少脑缺血时神经元的损伤、保护/恶化缺血器官、抗肿瘤以及抗新生血管的形成作用等。这些非镇痛效应为临床上扩大帕瑞昔布钠的应用范围,提供了理论依据。本文对帕瑞昔布钠近年来的作用机制以及最新进展进行综述。     

孕酮对脑损伤神经保护作用的Meta分析

目的 评价孕酮对脑损伤的神经保护作用.方法 计算机检索2005～2014年关于孕酮治疗创伤性脑损伤(TBI)的随机对照临床试验,并用Revman 5.1软件对符合纳入标准的研究进行系统评价.结果 本研究共纳入3个研究,Meta分析显示:孕酮和安慰剂对TBI患者的预后有差异性,且差异有统计学意义[病死率和格拉斯哥预后量表评分(4～5分)RR (95％CI)值分别为0.6(0.41～0.88)、1.61(1.18～2.27),格拉斯哥昏迷量表评分均数差(MD)值为0.87 (0.24～1.51)].结论 孕酮能降低TBI患者病死率,提高格拉斯哥预后量表和格拉斯哥昏迷量表评分,从而改善预后,促进患者神经功能恢复.     

重视青光眼性视神经保护的基础研究

青光眼是居世界首位的不可逆性致盲性眼病。虽然临床中唯一被认可的降眼压治疗可以延缓疾病进展,但大部分患者的视力损害仍日益加剧。针对这一棘手的问题,旨在直接保护视网膜终末受累细胞的"视神经保护"研究正如火如荼地开展。为进一步明确青光眼性视神经保护基础研究面临的问题,本文就目前该方面的研究现状进行简要总结,并主要针对基础研究中所遇到的关键性问题进行论述,以期提高研究工作者对青光眼性视神经保护的认识,为进一步有效的临床治疗干预靶点提供有力依据。     

Aβ induces its own prion protein N-terminal fragment (PrPN1)–mediated neutralization in amorphous aggregates

Plasma membrane cellular prion protein (PrP^C) is a high-affinity receptor for toxic soluble amyloid-β (Aβ) oligomers that mediates synaptic dysfunction. Secreted forms of PrP^C resulting from PrP^C α-cleavage (PrPN1) or shedding (shed PrP^C) display neuroprotective activity in neuronal cultures and in mouse models of Aβ-induced neuronal dysfunction. In vitro, recombinant PrPN1 and PrP inhibit Aβ fibrillization. However, the mechanism by which PrPN1 and shed PrP^C neutralize Aβ oligomers is unclear, and evidence of such neuroprotective activity in Alzheimer's disease (AD) patients is lacking. Here, we show that PrPN1 association with Aβ causes a conformational change resulting in the formation of amorphous and insoluble aggregates that are not compatible with the assembly of Aβs. Using postmortem brain tissues of AD patients, we were able to coimmunoprecipitate Aβ with PrP^C molecules and observed a coaggregation of Aβ and PrPN1 in the guanidine-extractable fraction presumably representing insoluble amyloid plaques. Furthermore, PrP^C α-cleavage is increased in AD brains, and we noticed a significant positive correlation between the levels of α-cleavage and of guanidine-extractable Aβ. These data strongly support the hypothesis that PrP^C α-cleavage is an endogenous neuroprotective mechanism in AD and support the development of PrP^C-derived peptides as therapeutic molecules for AD.     

The monoacylglycerol lipase inhibitor JZL184 is neuroprotective and alters glial cell phenotype in the chronic MPTP mouse model

Changes in cannabinoid receptor expression and concentration of endocannabinoids have been described in Parkinson's disease; however, it remains unclear whether they contribute to, or result from, the disease process. To evaluate whether targeting the endocannabinoid system could provide potential benefits in the treatment of the disease, the effect of a monoacylglycerol lipase inhibitor that prevents degradation of 2-arachidonyl-glycerol was tested in mice treated chronically with probenecid and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTPp). Chronic administration of the compound, JZL184 (8 mg/kg), prevented MPTPp-induced motor impairment and preserved the nigrostriatal pathway. Furthermore, none of the hypokinetic effects associated with cannabinoid receptor agonism were observed. In the striatum and substantia nigra pars compacta, MPTPp animals treated with JZL184 exhibited astroglial and microglial phenotypic changes that were accompanied by increases in TGFβ messenger RNA expression and in glial cell-derived neurotrophic factor messenger RNA and protein levels. JZL184 induced an increase in β-catenin translocation to the nucleus, implicating the Wnt/catenin pathway. Together, these results demonstrate a potent neuroprotective effect of JZL184 on the nigrostriatal pathway of parkinsonian animals, likely involving restorative astroglia and microglia activation and the release of neuroprotective and antiinflammatory molecules.     

Neuroprotection in the Preterm Infant: Further Understanding of the Short- and Long-term Implications for Brain Development

Neuroprotection is not a new term; it has been around for a considerable length of time in the laboratory and scientific world. It is, however, a new term in the clinical environment of the neonatal intensive care unit. Over time, the definition of neuroprotection has become more global, and as such, many of the developmental supportive activities now found in many neonatal intensive care units can be said to be neuroprotective. As we learn more about how the brain develops, we are more able to support and enhance its appropriate development in ways that lead to optimal outcomes. Neuroprotective strategies are one such avenue that needs further attention in the clinical setting.