title: Severity-Dependent Long-Term Spatial Learning-Memory Impairment in a Mouse Model of Traumatic Brain Injury.
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.
authors.affiliation: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
authors.forename: Chengrui
authors.initials: C
authors.lastname: An
authors.affiliation: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.|Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.|Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Pu
authors.affiliation: Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
authors.forename: Dandan
authors.initials: D
authors.lastname: Hong
authors.affiliation: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.|Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China. yqgao@shmu.edu.cn.|Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA. yqgao@shmu.edu.cn.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D012720:Severity of Illness Index; D065853:Spatial Learning / Q000502:physiology*
chemical_list: D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; C051774:neurofilament protein H
keywords: Hippocampus; Long-term spatial learning-memory deficits; Traumatic brain injury; White matter injury