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创伤性脑损伤后小鼠早期神经行为变化的自动监测

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

作者信息

Qu Wenrui, Liu Nai-Kui, Xie Xin-Min Simon, Li Rui, Xu Xiao-Ming

机构信息

Hand & Foot Surgery and Reparative & Reconstructive Surgery Center, Orthopaedic Hospital of the Second Hospital of Jilin University, Changchun, Jilin Province, China; Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Goodman Campbell Brain and Spine, Indianapolis, IN, USA.

Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Goodman Campbell Brain and Spine, Indianapolis, IN, USA.

出版信息

Neural Regen Res. 2016 Feb;11(2):248-56. doi: 10.4103/1673-5374.177732.

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.

摘要

创伤性脑损伤常导致多种行为和情绪障碍,这些障碍可能发展为慢性疾病。因此,有必要转向识别早期症状,这些症状有助于预测创伤性脑损伤患者在早期干预后的创伤性脑损伤结局和行为终点。在本研究中,我们使用了SmartCage系统,这是一种自动化定量方法,用于评估小鼠在创伤性脑损伤早期在家笼中的行为变化。对成年雌性C57BL/6小鼠进行中度控制性皮质撞击(CCI)损伤。然后在CCI后的第1、2和7天对小鼠进行一系列行为评估,包括神经学评分、运动活动、睡眠/觉醒状态和焦虑样行为。在最后一次评估后的第7天进行组织学分析。CCI组在损伤后第1天和第2天的自发活动显著减少。CCI组在黑暗和明亮周期中花费的睡眠时间平均百分比均显著高于假手术组。对于焦虑样行为,CCI组在明亮隔室中花费的时间以及在黑暗/明亮隔室之间的转换次数均显著低于假手术组。此外,遭受CCI的小鼠表现出更喜欢待在黑暗/明亮笼子的黑暗隔室中。CCI小鼠的神经学评分降低且存在组织学异常,这与自动化行为评估密切相关。我们的研究结果表明,自动化的SmartCage系统为创伤性脑损伤后小鼠的早期行为变化提供了敏感且客观的测量方法。

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