中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (2): 248-256.doi: 10.4103/1673-5374.177732

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

自动定量分析系统检测创伤性脑外伤后的早期行为学改变

  

  • 收稿日期:2015-12-09 出版日期:2016-02-15 发布日期:2016-02-15

Automated monitoring of early neurobehavioral changes in mice following traumatic brain injury

Wenrui Qu 1, 2, 3, 4, 5, Nai-kui Liu 2, 4, 5, Xin-min (Simon) Xie 6, Rui Li 1, Xiao-ming Xu 2, 3, 4, 5   

  1. 1 Hand & Foot Surgery and Reparative & Reconstructive Surgery Center, Orthopaedic Hospital of the Second Hospital of Jilin University,
    Changchun, Jilin Province, China
    2 Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA
    3 Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
    4 Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA
    5 Goodman Campbell Brain and Spine, Indianapolis, IN, USA
    6 AfaSci Research Laboratories, Redwood City, CA, USA
  • Received:2015-12-09 Online:2016-02-15 Published:2016-02-15
  • Contact: Rui Li, M.D., Ph.D. or Xiao-ming Xu, M.D., Ph.D., 13304321102@qq.com or xu26@iupui.edu.
  • Supported by:

    This work was supported by NIH NS073636 (RS/XMX), NS059622, DOD CDMRP W81XWH-12-1-0562, DVA 1I01BX002356-01A1,Craig H Neilsen Foundation 296749, Indiana Spinal Cord and Brain Injury Research Foundation and Mari Hulman George Endowment Funds (XMX), and by the State of Indiana (ISDH, Grant # A70-2-079609, A70-9-079138 and A70-5-0791033; NKL). This work was also supported by a grant from China Scholarship Council (CSC-201306170108) to WQ.

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摘要：

创伤性脑损伤可导致一系列行为和情绪障碍，进而发展呈慢性障碍。因此需要在转变前识别这些症状，可以辅助预测创伤性脑损伤的结局以及对创伤性脑损伤患者进行早期干预以改善行为终点。我们使用自动定量分析SmartCage系统观察在熟悉笼舍中活动的创伤性脑损伤早期小鼠的行为变化。实验对雌性C57BL/6成年小鼠进行适当控制大脑皮质损伤，在损伤后1，2，7d进行神经评分、自发活动、醒睡状态、焦虑样行为等行为测试，同时在损伤后7d时进行病理学分析。结果发现：(1)损伤后小鼠自发运动明显减少，平均睡眠时间延长；(2)焦虑实验中在光照环境中时间减少，光暗间穿梭次数明显降低，偏好在黑暗环境中长时间停留，且上述结果与神经评分及病理变化存在明显相关性；(3)此结果表明SmartCage系统可对创伤性脑损伤早期行为进行灵敏且客观的分析。

关键词: 神经再生, 创伤性脑损伤, 大脑皮质损伤, 自发行为, 运动活动, 焦虑, 眠, 探索

Abstract:

Traumatic brain injury often causes a variety of behavioral and emotional impairments that can develop into chronic disorders. Therefore, there is a need to shift towards identifying early symptoms that can aid in the prediction of traumatic brain injury outcomes and behavioral
endpoints in patients with traumatic brain injury after early interventions. In this study, we used the SmartCage system, an automated quantitative approach to assess behavior alterations in mice during an early phase of traumatic brain injury in their home cages. Female C57BL/6 adult mice were subjected to moderate controlled cortical impact (CCI) injury. The mice then received a battery of behavioral assessments including neurological score, locomotor activity, sleep/wake states, and anxiety-like behaviors on days 1, 2, and 7 after CCI. Histological analysis was performed on day 7 after the last assessment. Spontaneous activities on days 1 and 2 after injury were significantly decreased in the CCI group. The average percentage of sleep time spent in both dark and light cycles were significantly higher in the CCI group than in the sham group. For anxiety-like behaviors, the time spent in a light compartment and the number of transitions between the dark/light compartments were all significantly reduced in the CCI group than in the sham group. In addition, the mice suffering from CCI exhibited a preference of staying in the dark compartment of a dark/light cage. The CCI mice showed reduced neurological score and histological abnormalities, which are well correlated to the automated behavioral assessments. Our findings demonstrate that the automated SmartCage system provides sensitive and objective measures for early behavior changes in mice following traumatic brain injury.

Key words: nerve regeneration, traumatic brain injury, controlled cortical impact, automated behavior, motor activity, anxiety, exploratory activity, sleep, neural regeneration