Kochanek Patrick M, Wallisch Jessica S, Bayır Hülya, Clark Robert S B
Departments of Critical Care Medicine, Anesthesiology, Pediatrics, Bioengineering, and Clinical and Translational Science, Safar Center for Resuscitation Research, Children's Hospital of Pittsburgh of UPMC, John G. Rangos Research Center, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.
Safar Center for Resuscitation Research, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.
Childs Nerv Syst. 2017 Oct;33(10):1693-1701. doi: 10.1007/s00381-017-3474-2. Epub 2017 Sep 6.
Despite the enormity of the problem and the lack of new therapies, research in the pre-clinical arena specifically using pediatric traumatic brain injury (TBI) models is limited. In this review, some of the key models addressing both the age spectrum of pediatric TBI and its unique injury mechanisms will be highlighted. Four topics will be addressed, namely, (1) unique facets of the developing brain important to TBI model development, (2) a description of some of the most commonly used pre-clinical models of severe pediatric TBI including work in both rodents and large animals, (3) a description of the pediatric models of mild TBI and repetitive mild TBI that are relatively new, and finally (4) a discussion of challenges, gaps, and potential future directions to further advance work in pediatric TBI models.
This narrative review on the topic of pediatric TBI models was based on review of PUBMED/Medline along with a synthesis of information on key factors in pre-clinical and clinical developmental brain injury that influence TBI modeling.
In the contemporary literature, six types of models have been used in rats including weight drop, fluid percussion injury (FPI), impact acceleration, controlled cortical impact (CCI), mechanical shaking, and closed head modifications of CCI. In mice, studies are largely restricted to CCI. In large animals, FPI and rotational injury have been used in piglets and shake injury has also been used in lambs. Most of the studies have been in severe injury models, although more recently, studies have begun to explore mild and repetitive mild injuries to study concussion.
Given the emerging importance of TBI in infants and children, the morbidity and mortality that is produced, along with its purported link to the development of chronic neurodegenerative diseases, studies in these models merit greater systematic investigations along with consortium-type approaches and long-term follow-up to translate new therapies to the bedside.
尽管小儿创伤性脑损伤（TBI）问题严重且缺乏新的治疗方法，但临床前领域专门使用小儿TBI模型的研究仍然有限。在本综述中，将重点介绍一些针对小儿TBI年龄范围及其独特损伤机制的关键模型。将讨论四个主题，即：（1）对TBI模型开发重要的发育中大脑的独特方面；（2）描述一些最常用的小儿重度TBI临床前模型，包括啮齿动物和大型动物的研究；（3）描述相对较新的小儿轻度TBI和重复性轻度TBI模型；最后（4）讨论进一步推进小儿TBI模型研究工作的挑战、差距和潜在未来方向。
本关于小儿TBI模型主题的叙述性综述基于对PUBMED/Medline的检索，并综合了临床前和临床发育性脑损伤中影响TBI建模的关键因素的信息。
在当代文献中，大鼠已使用六种模型，包括重物坠落、液压冲击伤（FPI）、撞击加速、控制性皮质撞击（CCI）、机械摇晃以及CCI的闭合性颅脑损伤改良模型。在小鼠中，研究主要限于CCI。在大型动物中，FPI和旋转损伤已用于仔猪，摇晃损伤也已用于羔羊。大多数研究集中在重度损伤模型，不过最近，研究已开始探索轻度和重复性轻度损伤以研究脑震荡。
鉴于TBI在婴幼儿中的重要性日益凸显，其所导致的发病率和死亡率，以及其与慢性神经退行性疾病发展的潜在关联，对这些模型的研究值得进行更系统的调查，采用联盟式方法并进行长期随访，以便将新疗法应用于临床。
