Repeated mild traumatic brain injury can cause acute neurologic impairment without overt structural damage in juvenile rats

被引:41
作者
Meconi, Alicia [1 ]
Wortman, Ryan C. [1 ]
Wright, David K. [2 ,3 ]
Neale, Katie J. [1 ]
Clarkson, Melissa [1 ]
Shultz, Sandy R. [1 ,2 ,3 ,4 ]
Christie, Brian R. [1 ,5 ,6 ,7 ]
机构
[1] Univ Victoria, Div Med Sci, Victoria, BC, Canada
[2] Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia
[3] Monash Univ, Dept Neurosci, Melbourne, Vic, Australia
[4] Univ Melbourne, Dept Med, Parkville, Vic, Australia
[5] Univ British Columbia, Ctr Brain Hlth, Vancouver, BC, Canada
[6] Univ British Columbia, Program Neurosci, Vancouver, BC, Canada
[7] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC, Canada
来源
PLOS ONE | 2018年 / 13卷 / 05期
基金
加拿大自然科学与工程研究理事会; 澳大利亚国家健康与医学研究理事会;
关键词
SPORT-RELATED CONCUSSION; COLLEGIATE FOOTBALL PLAYERS; CLOSED-HEAD-INJURY; HIGH-SCHOOL; NEUROCOGNITIVE PERFORMANCE; HYPERPHOSPHORYLATED TAU; POSTCONCUSSION SYNDROME; PROFESSIONAL FOOTBALL; RECURRENT CONCUSSION; OXIDATIVE STRESS;
D O I
10.1371/journal.pone.0197187
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Repeated concussion is becoming increasingly recognized as a serious public health concern around the world. Moreover, there is a greater awareness amongst health professionals of the potential for repeated pediatric concussions to detrimentally alter the structure and function of the developing brain. To better study this issue, we developed an awake closed head injury (ACHI) model that enabled repeated concussions to be performed reliably and reproducibly in juvenile rats. A neurological assessment protocol (NAP) score was generated immediately after each ACHI to help quantify the cumulative effects of repeated injury on level of consciousness, and basic motor and reflexive capacity. Here we show that we can produce a repeated ACHI (4 impacts in two days) in both male and female juvenile rats without significant mortality or pain. We show that both single and repeated injuries produce acute neurological deficits resembling clinical concussion symptoms that can be quantified using the NAP score. Behavioural analyses indicate repeated ACHI acutely impaired spatial memory in the Barnes maze, and an interesting sex effect was revealed as memory impairment correlated moderately with poorer NAP score performance in a subset of females. These cognitive impairments occurred in the absence of motor impairments on the Rotarod, or emotional changes in the open field and elevated plus mazes. Cresyl violet histology and structural magnetic resonance imaging (MRI) indicated that repeated ACHI did not produce significant structural damage. MRI also confirmed there was no volumetric loss in the cortex, hippocampus, or corpus callosum of animals at 1 or 7 days post-ACHI. Together these data indicate that the ACHI model can provide a reliable, high throughput means to study the effects of concussions in juvenile rats.
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页数:24
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