Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA.
Brain Res. 2025 Jan 1;1846:149281. doi: 10.1016/j.brainres.2024.149281. Epub 2024 Oct 16.
Environmental enrichment (EE) consists of increased living space, complex stimuli, and social interaction that collectively confer neurobehavioral benefits in preclinical models of traumatic brain injury (TBI). The typical EE approach entails implementation immediately after surgery and continual exposure, which is not clinically applicable, as TBI patients often only receive rehabilitation after critical care, and then only for a few hours per day. We are focused on developing a clinically relevant model of neurorehabilitation by refining the timing of initiation and duration of EE exposure after TBI. The goal of this experiment is to compare the typical EE approach to paradigms where EE is delayed by 3 or 7 days after TBI and then provided for only 6 h per day, which better mimics the clinic. The hypothesis is that the delayed-and-abbreviated EE paradigms will promote neurobehavioral benefits like the typical approach of immediate-and-continuous exposure. To test the hypothesis, anesthetized adult male rats underwent a controlled cortical impact of moderate severity (2.8 mm deformation at 4 m/s) or sham injury and then were randomly assigned to post-operative EE or standard (STD) housing. Motor ability, spatial learning, and memory retention were assessed. The hypothesis was confirmed as all EE-treated groups performed better than the STD group in all behavioral assessments (p < 0.05) and did not differ from one another (p > 0.05). The ability of EE to provide significant behavioral benefits even when delayed and delivered in moderation affords further support for EE as a preclinical model of neurorehabilitation and offers greater insight into the length of the therapeutic window.
环境丰富(EE)包括增加生活空间、复杂刺激和社交互动,这些共同为创伤性脑损伤(TBI)的临床前模型带来神经行为益处。典型的 EE 方法需要在手术后立即实施,并持续暴露,这在临床上是不可行的,因为 TBI 患者通常仅在重症监护后接受康复治疗,而且每天只有几个小时。我们专注于通过改进 TBI 后 EE 暴露的开始时间和持续时间来开发一种更具临床相关性的神经康复模型。该实验的目的是比较典型的 EE 方法与 EE 在 TBI 后延迟 3 或 7 天开始并每天仅提供 6 小时的范例,这更能模拟临床情况。假设是,延迟和简短的 EE 范例将促进神经行为益处,就像典型的立即和连续暴露方法一样。为了验证假设,麻醉的成年雄性大鼠接受了中度严重程度的皮质撞击(4 m/s 时 2.8 毫米变形)或假损伤,然后随机分配到术后 EE 或标准(STD)饲养组。运动能力、空间学习和记忆保留能力进行评估。假设得到了证实,因为所有接受 EE 治疗的组在所有行为评估中的表现均优于 STD 组(p<0.05),并且彼此之间没有差异(p>0.05)。EE 即使在延迟和适度提供的情况下也能提供显著的行为益处,这进一步支持 EE 作为神经康复的临床前模型,并为治疗窗口的长度提供了更深入的了解。