Environmental enrichment and amantadine confer individual but nonadditive enhancements in motor and spatial learning after controlled cortical impact injury
Environmental enrichment and amantadine confer individual but nonadditive enhancements in motor and spatial learning after controlled cortical impact injury
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DOI：
10.1016/j.brainres.2019.03.007
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发表时间：
2019-07-01
期刊：
影响因子：
2.9
通讯作者：
Kline, Anthony E.
中科院分区：
文献类型：
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作者：
Bleimeister, Isabel H.;Wolff, Mia;Kline, Anthony E.
环境富集（EE）和金刚烷胺（AMT）增强实验性创伤性脑损伤（TBI）后的运动和认知结果。然而，没有关于这两种疗法联合使用的效果的数据。因此，本研究的目的是在TBI后将联合收割机EE和AMT结合起来，以确定它们的净效应是否进一步增强运动和认知表现。麻醉的成年雄性大鼠接受中等严重程度的皮质撞击或假损伤，然后随机分配至EE或标准（STD）圈养，每天一次给予AMT（20 mg/kg; i. p.）或盐水媒介物（VEH，lmL/kg; i. p.）伤后24 h开始，持续19天。分别在术后第1-5天和第14-19天评估运动和认知功能。在第21天定量皮质病变体积。无论治疗如何，假手术组之间均无统计学差异，因此汇总了数据。EE、AMT及其组合（EE + AMT）改善了平衡木平衡，但只有EE和EE + AMT增强了平衡木行走。相对于VEH治疗的STD对照，所有三种治疗模式均改善了空间学习和记忆（p < 0.05）。无论治疗如何，EE组之间均无差异，但在平衡木行走和空间学习方面均优于AMT治疗的STD组（p < 0.05）。两个EE组相对于STD容纳的AMT和VEH组同等地减少皮质病变体积（p < 0.05）。结果表明，尽管EE + AMT本身是有益的，但在TBI后不会提供额外的益处。重要的是要注意，使用当前的治疗和行为方案缺乏累加效应并不会减损每种单独治疗的益处。这些发现为未来的联合研究提供了见解。
Environmental enrichment (EE) and amantadine (AMT) enhance motor and cognitive outcome after experimental traumatic brain injury (TBI). However, there are no data on the effects of combining these two therapies. Hence, the aim of the current study was to combine EE and AMT after TBI to determine if their net effect further enhances motor and cognitive performance. Anesthetized adult male rats received either a cortical impact of moderate severity or sham injury and then were randomly assigned to EE or standard (STD) housing and once daily administration of AMT (20 mg/kg; i.p.) or saline vehicle (VEH, 1 mL/kg; i.p.) beginning 24 h after injury for 19 days. Motor and cognitive function were assessed on post-surgical days 1-5 and 14-19, respectively. Cortical lesion volume was quantified on day 21. There were no statistical differences among the sham groups regardless of therapy, so the data were pooled. EE, AMT, and their combination (EE + AMT) improved beam balance, but only EE and EE + AMT enhanced beam-walking. All three treatment paradigms improved spatial learning and memory relative to the VEH-treated STD controls (p < 0.05). No differences were revealed between the EE groups, regardless of treatment, but both were better than the AMT-treated STD group on beam walking and spatial learning (p < 0.05). Both EE groups equally reduced cortical lesion volume relative to the STD-housed AMT and VEH groups (p < 0.05). The results indicate that although beneficial on their own, EE + AMT do not provide additional benefits after TBI. It is important to note that the lack of additive effects using the current treatment and behavioral protocols does not detract from the benefits of each individual therapy. The findings provide insight for future combination studies.