Ojo Joseph O, Mouzon Benoit C, Crawford Fiona
Roskamp Institute, Sarasota, FL 34243, USA; The Open University, Department of Life Sciences, Milton Keynes MK7 6AA, UK; Chronic Effects of Neurotrauma Consortium, USA.
Roskamp Institute, Sarasota, FL 34243, USA; The Open University, Department of Life Sciences, Milton Keynes MK7 6AA, UK; James A. Haley Veterans Administration Medical Center, Tampa, FL 33612, USA; Chronic Effects of Neurotrauma Consortium, USA.
Exp Neurol. 2016 Jan;275 Pt 3:389-404. doi: 10.1016/j.expneurol.2015.06.003. Epub 2015 Jun 6.
Chronic traumatic encephalopathy (CTE) is a neurological and psychiatric condition marked by preferential perivascular foci of neurofibrillary and glial tangles (composed of hyperphosphorylated-tau proteins) in the depths of the sulci. Recent retrospective case series published over the last decade on athletes and military personnel have added considerably to our clinical and histopathological knowledge of CTE. This has marked a vital turning point in the traumatic brain injury (TBI) field, raising public awareness of the potential long-term effects of mild and moderate repetitive TBI, which has been recognized as one of the major risk factors associated with CTE. Although these human studies have been informative, their retrospective design carries certain inherent limitations that should be cautiously interpreted. In particular, the current overriding issue in the CTE literature remains confusing in regard to appropriate definitions of terminology, variability in individual pathologies and the potential case selection bias in autopsy based studies. There are currently no epidemiological or prospective studies on CTE. Controlled preclinical studies in animals therefore provide an alternative means for specifically interrogating aspects of CTE pathogenesis. In this article, we review the current literature and discuss difficulties and challenges of developing in-vivo TBI experimental paradigms to explore the link between repetitive head trauma and tau-dependent changes. We provide our current opinion list of recommended features to consider for successfully modeling CTE in animals to better understand the pathobiology and develop therapeutics and diagnostics, and critical factors, which might influence outcome. We finally discuss the possible directions of future experimental research in the repetitive TBI/CTE field.
慢性创伤性脑病（CTE）是一种神经和精神疾病，其特征是在脑沟深处存在由神经原纤维和胶质缠结（由过度磷酸化的tau蛋白组成）构成的血管周围病灶。过去十年发表的关于运动员和军人的回顾性病例系列研究极大地丰富了我们对CTE的临床和组织病理学认识。这标志着创伤性脑损伤（TBI）领域的一个重要转折点，提高了公众对轻度和中度重复性TBI潜在长期影响的认识，而这种影响已被认为是与CTE相关的主要危险因素之一。尽管这些人体研究提供了有价值的信息，但它们的回顾性设计存在某些固有局限性，应谨慎解读。特别是，CTE文献中当前的首要问题在术语的恰当定义、个体病理变化的多样性以及基于尸检研究的潜在病例选择偏差方面仍然令人困惑。目前尚无关于CTE的流行病学或前瞻性研究。因此，动物体内的对照临床前研究为专门探究CTE发病机制的各个方面提供了另一种手段。在本文中，我们回顾了当前的文献，并讨论了开发体内TBI实验范式以探索重复性头部创伤与tau蛋白依赖性变化之间联系的困难和挑战。我们提供了当前的观点列表，列出了在动物身上成功建立CTE模型以更好地理解病理生物学并开发治疗方法和诊断方法时应考虑的推荐特征，以及可能影响结果的关键因素。我们最后讨论了重复性TBI/CTE领域未来实验研究的可能方向。
