Neural Regeneration Research ›› 2016, Vol. 11 ›› Issue (2): 248-256.doi: 10.4103/1673-5374.177732

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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.

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