Combining Enriched Environment, Progesterone, and Embryonic Neural Stem Cell Therapy Improves Recovery after Brain Injury
Combining Enriched Environment, Progesterone, and Embryonic Neural Stem Cell Therapy Improves Recovery after Brain Injury
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DOI：
10.1089/neu.2014.3618
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发表时间：
2015-07-15
影响因子：
4.2
通讯作者：
Smith, Jeffrey S.
中科院分区：
文献类型：
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作者：
Nudi, Evan T.;Jacqmain, Justin;Smith, Jeffrey S.
每年有数以百万计的人受到创伤性脑损伤(TBI)的影响，目前还没有任何治疗方法在临床上显示出改善疗效的效果。最近的研究表明，丰富的环境(EE)、胚胎神经干细胞(ENSC)和孕酮(PROG)可以改善脑外伤后的功能结果，此外，一些研究人员建议，综合治疗方法可能比单一治疗方法更有效。本研究的目的是确定损伤后EE、黄体酮治疗或eNSC移植的不同组合是否比单一治疗更能改善功能结果。对大鼠进行受控皮质撞击，在内侧额叶皮质造成损伤。然后将大鼠置于EE或标准环境中，伤后4h给予黄体酮10 mg/kg或赋形剂注射，首次注射后每隔12h注射一次，持续72h。手术后7天，用eNSCs或培养液移植大鼠。然后对大鼠进行旷场测试、Barnes迷宫、Morris水迷宫和旋转杆任务。在接受综合治疗的动物的大多数行为任务中，功能结果都得到了改善。这一效果在联合EE的治疗中尤为显著。免疫组织化学显示移植的eNSCs存活、迁移，并显示神经表型。这些数据表明，颅脑损伤后的综合治疗方法可以更大程度地改善功能恢复。此外，当综合疗法与EE相结合时，对恢复的影响增强，导致更大的功能恢复。
Millions of persons every year are affected by traumatic brain injury (TBI), and currently no therapies have shown efficacy in improving outcomes clinically. Recent research has suggested that enriched environments (EE), embryonic neural stem cells (eNSC), and progesterone (PROG) improve functional outcomes after TBI, and further, several investigators have suggested that a polytherapuetic approach may have greater efficacy than a single therapy. The purpose of the current study was to determine if varying combinations of post-injury EE, progesterone therapy, or eNSC transplantation would improve functional outcomes over just a single therapy. A controlled cortical impact was performed in rats to create a lesion in the medial frontal cortex. The rats were then placed in either EE or standard environments and administered 10mg/kg progesterone or vehicle injections 4h post-injury and every 12h for 72h after the initial injection. Seven days after the surgery, rats were transplanted with either eNSCs or media. Rats were then tested on the open field test, Barnes maze, Morris water maze, and Rotor-Rod tasks. Improved functional outcomes were shown on a majority of the behavioral tasks in animals that received a combination of therapies. This effect was especially prominent with therapies that were combined with EE. Immunohistochemistry showed that the transplanted eNSCs survived, migrated, and displayed neural phenotypes. These data suggest that a poly-therapeutic approach after TBI improves functional recovery to a greater magnitude. Moreover, when polytherapies are combined with EE, the effects on recovery are enhanced, leading to greater recovery of function.