Combining the Antipsychotic Drug Haloperidol and Environmental Enrichment after Traumatic Brain Injury Is a Double-Edged Sword
Combining the Antipsychotic Drug Haloperidol and Environmental Enrichment after Traumatic Brain Injury Is a Double-Edged Sword
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DOI：
10.1089/neu.2016.4417
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发表时间：
2017-01-15
影响因子：
4.2
通讯作者：
Kline, Anthony E.
中科院分区：
文献类型：
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作者：
Folweiler, Kaitlin A.;Bondi, Corina O.;Kline, Anthony E.
环境富集（EE）在实验性创伤性脑损伤（TBI）后具有显着的益处。相反，抗精神病药物（APD）氟哌啶醇（HAL）对神经行为和认知恢复产生有害影响。然而，神经康复和激动的管理是TBI患者治疗策略的组成部分。因此，本研究的目的是确定这两种治疗方法如何相互作用并影响运动和认知恢复。麻醉的成年雄性大鼠接受受控的皮质撞击（以4 m/sec的速度2.8 mm组织变形）或假损伤，然后在EE或标准（STD）条件下饲养时，从术后24 h开始提供HAL（0.5 mg/kg;腹膜内[IP]）或溶媒（VEH; 1 mL/kg; IP），每天一次，持续19天。分别在损伤后第1-5天和第14-19天评估平衡/行走和Morris水迷宫性能，随后立即定量皮质病变体积。数据显示了预期和意外的结果。毫不奇怪，接受EE的TBI组的表现明显好于STD收容组，而TBI + STD + HAL组的表现比TBI + STD + VEH组差（p < 0.05）。令人惊讶的是，EE的治疗效果因HAL的伴随给药而大大降低。各组间皮质病变体积无差异（p > 0.05）。这些研究结果的潜在临床意义表明，对接受神经康复治疗的患者给予HAL可能是一把双刃剑，因为在康复治疗安全开始和执行之前必须控制躁动，但其使用可能会影响治疗效果。
Environmental enrichment (EE) confers significant benefits after experimental traumatic brain injury (TBI). In contrast, the antipsychotic drug (APD) haloperidol (HAL) exerts deleterious effects on neurobehavioral and cognitive recovery. Neurorehabilitation and management of agitation, however, are integral components of the treatment strategy for patients with TBI. Hence, the goal of this study was to determine how the two therapeutic approaches interact and influence motor and cognitive recovery. Anesthetized adult male rats received a controlled cortical impact (2.8mmtissue deformation at 4 m/sec) or sham injury and then were provided HAL (0.5 mg/kg; intraperitoneally [IP]) or vehicle (VEH; 1 mL/kg; IP) commencing 24 h after surgery and once daily for 19 days while housed in EE or standard (STD) conditions. Beam balance/walk and Morris water maze performance were assessed on post-injury days 1-5 and 14-19, respectively, followed immediately by quantification of cortical lesion volumes. The data revealed both expected and unexpected findings. It was not surprising that the TBI groups receiving EE performed significantly better than those in STD housing and that the TBI + STD + HAL group performed worse than the TBI + STD + VEH group (p < 0.05). What was surprising was that the therapeutic effects of EE were greatly reduced by concomitant administration of HAL. No differences in cortical lesion volumes were observed among the groups (p > 0.05). The potential clinical implications of these findings suggest that administering HAL to patients undergoing neurorehabilitation may be a double-edged sword because agitation must be controlled before rehabilitation can be safely initiated and executed, but its use may compromise therapeutic efficacy.