中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (6): 997-1003.doi: 10.4103/1673-5374.250579

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

构建分级控制性皮质损伤模型小鼠:急性组织病理学反应及长期行为学表现

  

  • 出版日期:2019-06-15 发布日期:2019-06-15
  • 基金资助:

    中国国家自然科学基金项目(81771332,81571184,81070990),上海市重中之重临床医学中心和重点学科建设计划(2017zz02017),上海市浦东新区卫生局重点学科(PWZxk2017-23,PWYgf2018-05),上海市浦东新区卫生局领先人才培养项目(PWR12018-07)

Acute histopathological responses and long-term behavioral outcomes in mice with graded controlled cortical impact injury

Si-Yi Xu 1, 2 , Min Liu 2 , Yang Gao 1 , Yang Cao 1 , Jin-Gang Bao 1 , Ying-Ying Lin 1 , Yong Wang 1 , Qi-Zhong Luo 1 , Ji-Yao Jiang 1 , Chun-Long Zhong 2   

  1. 1 Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
    2 Department of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
  • Online:2019-06-15 Published:2019-06-15
  • Contact: Chun-Long Zhong, MD, PhD, drchunlongzhong@126.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81771332, 81571184, 81070990 (all to CLZ); the Shanghai Key Medical Discipline for Critical Care Medicine, China, No. 2017zz02017 (to CLZ); the Key Discipline Construction Project of Pudong Health Bureau of Shanghai of China, No. PWZxk2017-23, PWYgf2018-05 (all to CLZ) and the Outstanding Leaders Training Pro¬gram of Pudong Health Bureau of Shanghai of China, No. PWR12018-07 (to CLZ).

摘要:

在脑创伤动物模型中,传统控制性脑皮质打击损伤模型动物,损伤后往往出现短期的运动功能障碍,而组织学检查确未发现严重皮质损害,因此该模型仍有待进一步完善。实验采用Pin-PointTM打击仪,对小鼠大脑皮质进行分级打击,试图建立一种分级继发性脑损伤小鼠模型,24h后,苏木精-伊红染色、FJB染色和免疫组化染色观察可见小鼠损伤侧海马CA2/3区打击部位脑组织的病理学表现、退变神经元的染色和神经胶质细胞数量存在差异。水迷宫实验和平衡木行走试验证实,模型小鼠的远期(14-28d)空间学习记忆能力和运动平衡能力损害的差异也与控制性脑皮质打击损伤后脑损伤程度相关。结果表明,模型小鼠在分级控制性脑皮质打击损伤后,受打击部位脑组织可发生相应的不同程度的急性组织病理应答,同时其远期的行为学表现也出现不同程度的损害。提示控制性脑皮质打击损伤可为评估创伤性脑损伤治疗策略提供灵敏、可靠、而且符合临床实际情况的动物模型。

orcid: 0000-0002-0605-7273 (Chun-Long Zhong)

关键词: 神经再生, 创伤性脑损伤, 分级控制性皮质损伤, 组织病理学, 行为学表现

Abstract:

While animal models of controlled cortical impact often display short-term motor dysfunction after injury, histological examinations do not show severe cortical damage. Thus, this model requires further improvement. Mice were subjected to injury at three severities using a Pin-Point™-controlled cortical impact device to establish secondary brain injury mouse models. Twenty-four hours after injury, hema¬toxylin-eosin staining, Fluoro-Jade B histofluorescence, and immunohistochemistry were performed for brain slices. Compared to the uninjured side, we observed differences of histopathological findings, neuronal degeneration, and glial cell number in the CA2 and CA3 regions of the hippocampus on the injured side. The Morris water maze task and beam-walking test verified long-term (14–28 days) spatial learning/memory and motor balance. To conclude, the histopathological responses were positively correlated with the degree of damage, as were the long-term behavioral manifestations after controlled cortical impact.

Key words: nerve regeneration, traumatic brain injury, controlled cortical impact, histopathology, behavioral manifestations, neural regeneration