Molecular mechanisms of cognitive dysfunction following traumatic brain injury.
Molecular mechanisms of cognitive dysfunction following traumatic brain injury.
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DOI：
10.3389/fnagi.2013.00029
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发表时间：
2013
影响因子：
4.8
通讯作者：
Tesco G
中科院分区：
文献类型：
--
作者：
Walker KR;Tesco G
创伤性脑损伤（TBI）由于认知缺陷（特别是在注意力、学习和记忆以及高阶执行功能方面）而导致显著残疾。TBI在慢性神经变性和神经变性疾病（包括阿尔茨海默病（AD）、帕金森病（PD）、肌萎缩性侧索硬化症（ALS）和最近的慢性创伤性脑病（CTE））的发展中的作用是特别重要的。然而，尽管做出了重大努力，但很少有治疗选择可以预防或逆转TBI后的认知障碍。在这篇综述中，我们提出了实验证据，已知的继发性损伤机制，有助于神经元细胞丢失，轴突损伤，突触功能障碍，因此认知功能障碍急性和慢性TBI。特别是，我们专注于TBI与两种形式的痴呆症：AD和CTE的发展机制。我们提供了TBI后参与调节Aβ和Tau的潜在分子机制的证据，并提供了这些机制在AD病理学中作用的证据。此外，我们提出了一种机制，通过该机制，作为TBI的直接结果产生的Aβ能够加剧继发性损伤机制，从而建立导致慢性神经变性的神经毒性级联反应。
Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration.