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Severity-Dependent Long-Term Spatial Learning-Memory Impairment in a Mouse Model of Traumatic Brain Injury

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Abstract

Traumatic brain injury (TBI) is a major cause of death and disability in young adults. Long-term mental disability often occurs in patients suffering moderate and severe TBI while not as frequent in the victims of mild TBI. To explore the potential mechanism underlying this severity-dependent cognitive deficit, we subjected C57/BL6 mice to different severities of controlled cortical impact (CCI) and assessed their learning-memory functions. The mice subjected to moderate and severe TBI exhibited significantly impaired long-term spatial learning-memory ability, which was accompanied by marked white matter injury and hippocampus damage. In contrast, long-term learning-memory deficits or structural abnormalities within the hippocampus or white matter were not significant in the case of mild TBI. According to a correlation analysis, the hippocampus or white matter injury severity was more relevant to Morris water maze outcome than tissue volume. This study revealed that long-term spatial learning-memory deficits are dependent on the severity of destruction in the white matter and hippocampus. Therapeutic strategies targeting both the white matter and hippocampus may be needed to improve the neurological functions in TBI victims.

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Acknowledgments

This project was supported by the Chinese Natural Science Foundation grants 81171149, 81371306, 81571285 (to Dr. Gao), and 81471332 (to Dr. Zhang); the Shanghai Committee of Science and Technology Support Program 14431907002 (to Dr. Gao); and the American Heart Association Scientist Development grant 13SDG14570025 (to Dr. Hu).

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Authors and Affiliations

  1. State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China

    Chengrui An, Xiaoyan Jiang, Hongjian Pu, Wenting Zhang, Xiaoming Hu & Yanqin Gao

  2. Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

    Xiaoyan Jiang, Hongjian Pu, Dandan Hong, Xiaoming Hu & Yanqin Gao

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  1. Chengrui An
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Correspondence to Yanqin Gao.

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All national and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.

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An, C., Jiang, X., Pu, H. et al. Severity-Dependent Long-Term Spatial Learning-Memory Impairment in a Mouse Model of Traumatic Brain Injury. Transl. Stroke Res. 7, 512–520 (2016). https://doi.org/10.1007/s12975-016-0483-5

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