Cortes Daniel, Pera Martin F
The Jackson Laboratory, Bar Harbor, ME, 04660, USA.
NPJ Regen Med. 2021 Jan 21;6(1):5. doi: 10.1038/s41536-020-00114-y.
Traumatic brain injury (TBI) is one of the leading causes of death among young people, and is increasingly prevalent in the aging population. Survivors of TBI face a spectrum of outcomes from short-term non-incapacitating injuries to long-lasting serious and deteriorating sequelae. TBI is a highly complex condition to treat; many variables can account for the observed heterogeneity in patient outcome. The limited success of neuroprotection strategies in the clinic has led to a new emphasis on neurorestorative approaches. In TBI, it is well recognized clinically that patients with similar lesions, age, and health status often display differences in recovery of function after injury. Despite this heterogeneity of outcomes in TBI, restorative treatment has remained generic. There is now a new emphasis on developing a personalized medicine approach in TBI, and this will require an improved understanding of how genetics impacts on long-term outcomes. Studies in animal model systems indicate clearly that the genetic background plays a role in determining the extent of recovery following an insult. A candidate gene approach in human studies has led to the identification of factors that can influence recovery. Here we review studies of the genetic basis for individual differences in functional recovery in the CNS in animals and man. The application of in vitro modeling with human cells and organoid cultures, along with whole-organism studies, will help to identify genes and networks that account for individual variation in recovery from brain injury, and will point the way towards the development of new therapeutic approaches.
创伤性脑损伤（TBI）是年轻人死亡的主要原因之一，并且在老年人群中越来越普遍。TBI幸存者面临着一系列后果，从短期无能力损伤到长期严重且不断恶化的后遗症。TBI是一种治疗起来非常复杂的病症；许多变量可以解释观察到的患者预后的异质性。临床上神经保护策略的有限成功导致了对神经修复方法的新重视。在TBI中，临床上已经充分认识到，具有相似损伤、年龄和健康状况的患者在受伤后的功能恢复方面往往存在差异。尽管TBI的预后存在这种异质性，但恢复性治疗仍然是通用的。现在人们重新强调在TBI中开发个性化医疗方法，这将需要更好地理解遗传学如何影响长期预后。动物模型系统的研究清楚地表明，遗传背景在决定损伤后恢复程度方面发挥着作用。人类研究中的候选基因方法已经导致了对可影响恢复的因素的识别。在这里，我们综述了动物和人类中枢神经系统功能恢复个体差异的遗传基础研究。使用人类细胞和类器官培养的体外建模以及全生物体研究的应用，将有助于识别解释脑损伤恢复个体差异的基因和网络，并将为新治疗方法的开发指明方向。
