Eagle Shawn R, Henry Rebecca J
Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
University College, Cork, Ireland.
Neurotrauma Rep. 2024 Jul 16;5(1):671-679. doi: 10.1089/neur.2024.0040. eCollection 2024.
A sizable proportion of patients with mild traumatic brain injury (mTBI) have persistent symptoms and functional impairments months to years following injury. This phenomenon is continually observed despite an explosion of research and interest in improving mTBI clinical outcomes over the last two decades. All pharmacological clinical trials to date have failed to demonstrate improved outcomes for mTBI. One possible explanation for these continued failures is an overly myopic approach to treating mTBI (i.e., testing the effect of a single drug with a specific mechanism on a group of people with highly heterogenous injuries). Clinical presentation and prognosis of mTBI vary considerably between patients, and yet we continue to assess group-level effects of a homogenized treatment. We need to utilize an equally complex treatment approach to match the extraordinary complexity of the human brain. Dynamical systems theory has been used to describe systems composed of multiple subsystems who function somewhat independently but are ultimately interconnected. This theory was popularized in the motor control literature as an overarching framework for how the mind and body connect to interact and move through the environment. However, the human body can be viewed as a dynamical system composed of multiple subsystems (i.e., organ systems) who have isolated functions, which are also codependent on the health and performance of other interconnected organ systems. In this perspective piece, we will use the example of mTBI in the obese patient to demonstrate how broadening our approach to treatment of the individual (and not necessarily the injury) may ultimately yield improved outcomes. Furthermore, we will explore clinical and pre-clinical evidence demonstrating multiple system interactions in the context of obesity and TBI and discuss how expanding our understanding of the mechanistic interplay between multiple organ systems may ultimately provide a more personalized treatment approach for this mTBI patient subpopulation.
相当一部分轻度创伤性脑损伤（mTBI）患者在受伤数月至数年之后仍有持续症状和功能障碍。尽管在过去二十年里，针对改善mTBI临床结局的研究和关注度激增，但这一现象仍不断被观察到。迄今为止，所有药物临床试验均未能证明对mTBI有改善的疗效。这些持续失败的一个可能解释是，治疗mTBI的方法过于短视（即测试一种具有特定机制的单一药物对一群具有高度异质性损伤的人的效果）。mTBI患者的临床表现和预后差异很大，但我们仍在评估同质化治疗的群体水平效应。我们需要采用同样复杂的治疗方法来匹配人类大脑的非凡复杂性。动态系统理论已被用于描述由多个子系统组成的系统，这些子系统在一定程度上独立运作，但最终相互关联。该理论在运动控制文献中作为一个总体框架而流行，用于解释思维与身体如何连接、相互作用并在环境中移动。然而，人体可被视为一个由多个子系统（即器官系统）组成的动态系统，这些子系统具有各自独立的功能，但也相互依赖于其他相互连接的器官系统的健康和功能表现。在这篇观点文章中，我们将以肥胖患者的mTBI为例，说明拓宽我们对个体（而非仅仅针对损伤）的治疗方法如何最终可能带来更好的治疗效果。此外，我们将探讨临床和临床前证据，这些证据表明在肥胖和TBI背景下存在多个系统的相互作用，并讨论如何扩展我们对多个器官系统之间机制性相互作用的理解，最终可能为这一mTBI患者亚群提供更个性化的治疗方法。
