中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (9): 1371-1372.doi: 10.4103/1673-5374.165219

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

老龄人群中的非类固醇抗炎药和神经保护:从线粒体所得

  

  • 收稿日期:2015-06-10 出版日期:2015-09-28 发布日期:2015-09-28

Non-steroidal anti-inflammatory drugs (NSAIDs) and neuroprotection in the elderly: a view from the mitochondria

María Calvo-Rodríguez, Lucía Núñez, Carlos Villalobos   

  1. Instituto de Biología y Genética Molecular (IBGM), Consejo Superior de Investigaciones Científicas (CSIC) and Universidad de Valladolid, c/ Sanz y Fores 3, 47003 Valladolid, Spain
  • Received:2015-06-10 Online:2015-09-28 Published:2015-09-28
  • Contact: Carlos Villalobos, Ph.D., carlosv@ibgm.uva.es.
  • Supported by:

    This work was supported by grants VA145U13, BIO/VA33/13, BIO103/VA45/11 from Junta de Castilla y León, Spain and BFU2012-37146 from Ministerio de Economía y Competitividad, Spain. MCR was supported by a pre-doctoral fellowship from Junta de Castilla y León, Spain and The European Social Fund.

摘要:

脑卒中和神经退行性变最重要的危险因素就是衰老。事实上,脑卒中后存活率的降低在很大程度上也与衰老有关。因此,脑动脉闭塞后的恢复会随着老化发生显著恶化,甚至正常的衰老构成也与神经元损伤和认知能力下降有关。目前我们仍对脑卒中和神经退行性疾病中老化导致的认知能力下降和神经元易受伤害机制知之甚少。该种最重要机制的其中之一是兴奋性毒性导致的神经功能障碍和死亡。这个过程在1969年最初由奥尔尼提出,基于对谷氨酸受体的过度刺激会导致过度活化和神经元损伤。这种过度刺激可以由谷氨酸的浓度增加或兴奋性氨基酸浓度轻微增加导致的受体长期活化。保护老化大脑不受损害仍然是神经学家和神经科学家的一大挑战。大量的基础和临床研究已经提供了强有力的证据,并提出了长时间使用非类固醇消炎药可以减少阿尔茨海默病的发病率。非类固醇消炎药在大鼠原代神经元培养物和海马切片中能够体外降低谷氨酸兴奋毒性,并在体内保护大鼠对鱼藤酮诱导的帕金森病。最近的证据表明,非类固醇消炎药甚至可能防止与人类相关的健康老龄化的认知能力下降。

Abstract:

The most important risk factor for stroke and neurodegeneration is aging. In fact, survival after stroke diminishes largely with aging. Thus, recovery after brain artery occlusion is dramatically worsened with aging and even normal aging is also associated with neuron damage and cognitive decline. Mechanisms by which aging promotes cognitive decline and susceptibility to neuron damage in stroke and neurodegeneration are largely unknown. One of the most important mechanisms contributing to neural dysfunction and death is excitotoxicity. This process, initially proposed by Olney in 1969, is based in that the excessive stimulation of glutamate receptors leads to hyperactivation and neuronal damage. This overstimulation may be due to increased concentration of glutamate, or prolonged activation of the receptors by a mild increase in the concentration of the excitatory amino acid.
Protecting the aging brain against damage remains a big challenge for neurologists and neuroscientists. Interestingly, a large number of basic and clinical studies have provided strong evidence indicating that the prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the incidence of Alzheimer's Disease, the most common form of dementia. NSAIDs also decrease glutamate excitotoxicity both in vitro, in rat primary neuronal cultures and hippocampal slices, and in vivo, protecting rats against rotenone-induced parkinsonism. Recent evidence suggests that NSAIDs may even protect against the cognitive decline associated to healthy aging in humans.