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 Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
Exp Neurol. 2025 Jan;383:114990. doi: 10.1016/j.expneurol.2024.114990. Epub 2024 Oct 9.
The robustness of environmental enrichment (EE) in ameliorating neurobehavioral and cognitive deficits after experimental traumatic brain injury (TBI) is unequivocal. What is equivocal is whether EE can function as a prophylactic to afford resiliency and neuroprotection against TBI. We hypothesized that pre-operative EE would yield a protective effect against TBI-induced motor, cognitive, and coping deficits, and that further improvements would be conferred when EE is provided before and after TBI. To test the hypotheses, adult male rats received either 4 weeks of EE or standard (STD) housing prior to undergoing a controlled cortical impact of moderate severity (2.8 mm deformation at 4 m/s) or sham injury while under anesthesia. After injury, the rats were randomly assigned to post-operative EE or STD housing. Motor ability, spatial learning, and memory retention were assessed by beam-walk and water maze tests, respectively. Active and passive behavioral coping strategies were evaluated with the shock probe defensive burying (SPDB) test. c-Fos and cortical lesion volume were also quantified. The post-TBI enrichment groups (EE + TBI + EE and STD + TBI + EE) did not differ (p > 0.05) and performed better than the post-TBI STD-housed groups (EE + TBI + STD and STD + TBI + STD) on motor and cognition (p < 0.05). The post-TBI STD groups did not differ, regardless of whether in EE or STD living conditions before injury (p > 0.05). Moreover, both post-TBI enrichment groups performed better in the SPDB test relative to the STD + TBI + STD group (p < 0.05). c-Fos + cells were upregulated in the ipsilateral CA in both pre-injury EE groups relative to the pre-injury STD groups (p < 0.05). No statistical differences were observed in cortical lesion volume among the groups. Overall, these data do not support the hypothesis as no neuroprotective effect was observed with 4 weeks of pre-operative EE and no additional benefit was achieved in the TBI group receiving both pre-and-post EE relative to the TBI group receiving only post-EE. However, the data do reinforce the consistency of post-TBI EE in producing robust neurobehavioral benefits, which further supports this paradigm as a relevant preclinical model of neurorehabilitation.
环境丰富（EE）在改善实验性创伤性脑损伤（TBI）后的神经行为和认知缺陷方面的稳健性是明确的。存在争议的是，EE 是否可以作为预防措施，提供对 TBI 的弹性和神经保护。我们假设术前 EE 将产生对抗 TBI 诱导的运动、认知和应对缺陷的保护作用，并且当在 TBI 之前和之后提供 EE 时会进一步改善。为了检验这些假设，成年雄性大鼠在接受中度严重程度的控制皮质撞击（4 m/s 时 2.8mm 变形）或假损伤之前，接受 4 周的 EE 或标准（STD）饲养。受伤后，大鼠被随机分配到术后 EE 或 STD 饲养。通过光束行走和水迷宫测试分别评估运动能力、空间学习和记忆保留。使用冲击探针防御埋藏（SPDB）测试评估主动和被动行为应对策略。还量化了 c-Fos 和皮质病变体积。TBI 后丰富组（EE+TBI+EE 和 STD+TBI+EE）之间没有差异（p>0.05），并且在运动和认知方面优于 TBI 后 STD 饲养组（EE+TBI+STD 和 STD+TBI+STD）（p<0.05）。TBI 后 STD 组之间没有差异，无论受伤前是在 EE 还是 STD 生活条件下（p>0.05）。此外，与 STD+TBI+STD 组相比，TBI 后丰富组在 SPDB 测试中的表现更好（p<0.05）。与受伤前的 STD 组相比，受伤前的 EE 组同侧 CA 中的 c-Fos+细胞上调（p<0.05）。各组之间皮质病变体积无统计学差异。总体而言，这些数据不支持假设，因为术前 4 周的 EE 没有观察到神经保护作用，并且与仅接受术后 EE 的 TBI 组相比，接受术前和术后 EE 的 TBI 组没有获得额外的益处。然而，数据确实加强了 TBI 后 EE 产生强大神经行为益处的一致性，这进一步支持了这种范式作为神经康复的相关临床前模型。
