Radabaugh Hannah L, LaPorte Megan J, Greene Anna M, Bondi Corina O, Lajud Naima, Kline Anthony E
Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15213, United States.
Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15213, United States; Neurobiology, University of Pittsburgh, Pittsburgh, PA 15213, United States; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA 15213, United States; Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15213, United States.
Exp Neurol. 2017 Aug;294:12-18. doi: 10.1016/j.expneurol.2017.04.013. Epub 2017 Apr 27.
The typical environmental enrichment (EE) paradigm, which consists of continuous exposure after experimental traumatic brain injury (TBI), promotes behavioral and histological benefits. However, rehabilitation is often abbreviated in the clinic and administered in multiple daily sessions. While recent studies have demonstrated that a once daily 6-hr bout of EE confers benefits comparable to continuous EE, breaking the therapy into two shorter sessions may increase novelty and ultimately enhance recovery. Hence, the aim of the study was to test the hypothesis that functional and histological outcomes will be significantly improved by daily preclinical neurorehabilitation consisting of two 3-hr periods of EE vs. a single 6-hr session. Anesthetized adult male rats received a controlled cortical impact of moderate-to-severe injury (2.8mm tissue deformation at 4m/s) or sham surgery and were then randomly assigned to groups receiving standard (STD) housing, a single 6-hr session of EE, or two 3-hr sessions of EE daily for 3weeks. Motor function (beam-balance/traversal) and acquisition of spatial learning/memory retention (Morris water maze) were assessed on post-operative days 1-5 and 14-19, respectively. Cortical lesion volume was quantified on day 21. Both EE conditions improved motor function and acquisition of spatial learning, and reduced cortical lesion volume relative to STD housing (p<0.05), but did not differ from one another in any endpoint (p>0.05). The findings replicate previous work showing that 6-hr of EE daily is sufficient to confer behavioral and histological benefits after TBI and extend the findings by demonstrating that the benefits are comparable regardless of how the 6-hrs of EE are accrued. The relevance of the finding is that it can be extrapolated to the clinic and may benefit patients who cannot endure a single extended period of neurorehabilitation.
典型的环境丰富化(EE)模式,即在实验性创伤性脑损伤(TBI)后持续暴露,可促进行为和组织学方面的改善。然而,在临床中康复治疗往往被缩短且分为多个每日疗程进行。虽然最近的研究表明,每天一次6小时的EE疗程所带来的益处与持续EE相当,但将治疗分为两个较短的疗程可能会增加新奇感并最终促进恢复。因此,本研究的目的是检验这样一个假设:与单次6小时疗程相比,每天由两个3小时的EE疗程组成的临床前神经康复治疗能显著改善功能和组织学结果。成年雄性大鼠接受中度至重度损伤(4米/秒时组织变形2.8毫米)的控制性皮质撞击或假手术,然后随机分为接受标准(STD)饲养环境、单次6小时EE疗程或每天两个3小时EE疗程的组,为期3周。分别在术后第1 - 5天和第14 - 19天评估运动功能(平衡木行走/穿越)以及空间学习/记忆保持能力的获得(莫里斯水迷宫)。在第21天对皮质损伤体积进行定量分析。与STD饲养环境相比,两种EE条件均改善了运动功能和空间学习能力的获得,并减小了皮质损伤体积(p<0.05),但在任何终点指标上两者之间均无差异(p>0.05)。这些发现重复了先前的研究结果,即每天6小时的EE足以在TBI后带来行为和组织学方面的益处,并且进一步表明,无论6小时的EE是如何累积的,其益处都是相当 的。该发现的意义在于它可以外推到临床,可能会使那些无法耐受单次长时间神经康复治疗的患者受益。