McDonald Matthew W, Hayward Kathryn S, Rosbergen Ingrid C M, Jeffers Matthew S, Corbett Dale
Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
Canadian Partnership for Stroke Recovery, Ottawa, ON, Canada.
Front Behav Neurosci. 2018 Jul 11;12:135. doi: 10.3389/fnbeh.2018.00135. eCollection 2018.
Environmental enrichment (EE) has been widely used as a means to enhance brain plasticity mechanisms (e.g., increased dendritic branching, synaptogenesis, etc.) and improve behavioral function in both normal and brain-damaged animals. In spite of the demonstrated efficacy of EE for enhancing brain plasticity, it has largely remained a laboratory phenomenon with little translation to the clinical setting. Impediments to the implementation of enrichment as an intervention for human stroke rehabilitation and a lack of clinical translation can be attributed to a number of factors not limited to: (i) concerns that EE is actually the "normal state" for animals, whereas standard housing is a form of impoverishment; (ii) difficulty in standardizing EE conditions across clinical sites; (iii) the exact mechanisms underlying the beneficial actions of enrichment are largely correlative in nature; (iv) a lack of knowledge concerning what aspects of enrichment (e.g., exercise, socialization, cognitive stimulation) represent the critical or active ingredients for enhancing brain plasticity; and (v) the required "dose" of enrichment is unknown, since most laboratory studies employ continuous periods of enrichment, a condition that most clinicians view as impractical. In this review article, we summarize preclinical stroke recovery studies that have successfully utilized EE to promote functional recovery and highlight the potential underlying mechanisms. Subsequently, we discuss how EE is being applied in a clinical setting and address differences in preclinical and clinical EE work to date. It is argued that the best way forward is through the careful alignment of preclinical and clinical rehabilitation research. A combination of both approaches will allow research to fully address gaps in knowledge and facilitate the implementation of EE to the clinical setting.
环境丰富化(EE)已被广泛用作一种手段,以增强正常动物和脑损伤动物的脑可塑性机制(例如,增加树突分支、突触形成等)并改善行为功能。尽管EE在增强脑可塑性方面已显示出功效,但它在很大程度上仍然只是一种实验室现象,很少转化到临床环境中。将丰富化作为人类中风康复干预措施实施存在障碍以及缺乏临床转化可归因于多种因素,包括但不限于:(i)担心EE实际上是动物的“正常状态”,而标准饲养是一种贫乏形式;(ii)在不同临床地点标准化EE条件存在困难;(iii)丰富化有益作用的具体机制在很大程度上本质上是相关性的;(iv)缺乏关于丰富化的哪些方面(例如,运动、社交、认知刺激)是增强脑可塑性的关键或有效成分的知识;以及(v)丰富化所需的“剂量”未知,因为大多数实验室研究采用连续的丰富化时间段,而大多数临床医生认为这种情况不切实际。在这篇综述文章中,我们总结了已成功利用EE促进功能恢复的临床前中风恢复研究,并强调了潜在的机制。随后,我们讨论了EE在临床环境中的应用方式,并阐述了迄今为止临床前和临床EE工作的差异。有人认为,前进的最佳途径是通过临床前和临床康复研究的仔细协调。两种方法的结合将使研究能够充分解决知识空白,并促进EE在临床环境中的实施。