Department of Neurology, Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA 15260, USA; Excellence Unit of the Institute of Genetics and Molecular Biology (IBGM) - Consejo Superior de Investigaciones Científicas, Valladolid 47003, Spain; Department of Biochemistry and Molecular Biology and Physiology, School of Medicine, University of Valladolid, Valladolid 47003, Spain.
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.
Exp Neurol. 2022 Nov;357:114204. doi: 10.1016/j.expneurol.2022.114204. Epub 2022 Aug 13.
Traumatic brain injury (TBI) causes persistent cognitive impairment and neurodegeneration. Environmental enrichment (EE) refers to a housing condition that promotes sensory and social stimulation and improves cognition and motor performance but the underlying mechanisms responsible for such beneficial effects are not well defined. In this study, anesthetized adult rats received either a moderate-to-severe controlled cortical impact (CCI) or sham surgery and then were housed in either EE or standard conditions. The results showed a significant increase in protein nitration and oxidation of lipids, impaired cognition and motor performance, and augmented N-methyl-d-aspartate receptor subtype-1 (NMDAR1) levels. However, EE initiated 24 h after CCI resulted in reduced oxidative insult and microglial activation and significant improvement in beam-balance/walk performance and both spatial learning and memory. We hypothesize that following TBI there is an upstream activation of NMDAR that promotes oxidative insult and an inflammatory response, thereby resulting in impaired behavioral functioning but EE may exert a neuroprotective effect via sustained downregulation of NMDAR1.
创伤性脑损伤 (TBI) 可导致持续的认知障碍和神经退行性变。环境丰富 (EE) 是指一种促进感觉和社会刺激、改善认知和运动表现的居住条件,但负责这种有益效果的潜在机制尚不清楚。在这项研究中,麻醉成年大鼠接受中度至重度皮质控制撞击 (CCI) 或假手术,然后分别置于 EE 或标准条件下。结果显示,蛋白质硝化和脂质氧化显著增加,认知和运动表现受损,N-甲基-D-天冬氨酸受体亚型-1 (NMDAR1) 水平升高。然而,CCI 后 24 小时开始的 EE 导致氧化损伤和小胶质细胞激活减少,平衡木/行走性能以及空间学习和记忆显著改善。我们假设,TBI 后,NMDAR 上游激活可促进氧化损伤和炎症反应,从而导致行为功能受损,但 EE 可能通过持续下调 NMDAR1 发挥神经保护作用。