Wei Zheng Zachory, Lee Jin Hwan, Zhang Yongbo, Zhu Yan Bing, Deveau Todd C, Gu Xiaohuan, Winter Megan M, Li Jimei, Wei Ling, Yu Shan Ping
Laboratories of Stem Cell Biology and Regenerative Medicine, Department of Neurology, Experimental Research Center and Neurological Disease Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Cell Transplant. 2016;25(5):797-809. doi: 10.3727/096368916X690403. Epub 2016 Jan 13.
Traumatic brain injury (TBI) is a common cause of mortality and long-term morbidity in children and adolescents. Posttraumatic stress disorder (PTSD) frequently develops in these patients, leading to a variety of neuropsychiatric syndromes. Currently, few therapeutic strategies are available to treat juveniles with PTSD and other developmental neuropsychiatric disorders. In the present investigation, postnatal day 14 (P14) Wistar rats were subjected to TBI induced by a controlled cortical impact (CCI) (velocity = 3 m/s, depth = 2.0 mm, contact time = 150 ms). This TBI injury resulted in not only cortical damages, but also posttrauma social behavior deficits. Three days after TBI, rats were treated with intracranial transplantation of either mouse iPSC-derived neural progenitor cells under normal culture conditions (N-iPSC-NPCs) or mouse iPSC-derived neural progenitor cells pretreated with hypoxic preconditioning (HP-iPSC-NPCs). Compared to TBI animals that received N-iPSC-NPCs or vehicle treatment, HP-iPSC-NPC-transplanted animals showed a unique benefit of improved performance in social interaction, social novelty, and social transmission of food preference tests. Western blotting showed that HP-iPSC-NPCs expressed significantly higher levels of the social behavior-related genes oxytocin and the oxytocin receptor. Overall, HP-iPSC-NPC transplantation exhibits a great potential as a regenerative therapy to improve neuropsychiatric outcomes after juvenile TBI.
创伤性脑损伤（TBI）是儿童和青少年死亡及长期发病的常见原因。创伤后应激障碍（PTSD）在这些患者中经常出现，导致各种神经精神综合征。目前，几乎没有治疗策略可用于治疗患有PTSD和其他发育性神经精神障碍的青少年。在本研究中，对出生后第14天（P14）的Wistar大鼠进行了控制性皮质撞击（CCI）诱导的TBI（速度 = 3 m/s，深度 = 2.0 mm，接触时间 = 150 ms）。这种TBI损伤不仅导致皮质损伤，还导致创伤后社交行为缺陷。TBI后三天，大鼠接受颅内移植正常培养条件下的小鼠iPSC衍生神经祖细胞（N-iPSC-NPCs）或经缺氧预处理（HP-iPSC-NPCs）的小鼠iPSC衍生神经祖细胞。与接受N-iPSC-NPCs或载体治疗的TBI动物相比，接受HP-iPSC-NPC移植的动物在社交互动、社交新奇性和食物偏好测试的社交传递方面表现出独特的改善优势。蛋白质印迹分析表明，HP-iPSC-NPCs表达的与社交行为相关的基因催产素和催产素受体水平显著更高。总体而言，HP-iPSC-NPC移植作为一种再生疗法，在改善青少年TBI后的神经精神结局方面具有巨大潜力。
