Environmental enrichment improves traumatic brain injury-induced behavioral phenotype and associated neurodegenerative process

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.This work was supported, in part, by the National Institutes of Health grant NS084967 (AEK), the Research Advisory Committee, Children's Hospital of Pittsburgh of UPMC (COB), the María Zambrano Excellence Program from the Ministry of Science and Innovation and the University of Valladolid, Spain (VT), and the Internationalization program of Junta de Castilla y Leon, Spain (CL-EI-2021-09 IBGM, VT)