PMID- 29738554
OWN - NLM
STAT- MEDLINE
DCOM- 20180801
LR  - 20240314
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 5
DP  - 2018
TI  - Repeated mild traumatic brain injury can cause acute neurologic impairment 
      without overt structural damage in juvenile rats.
PG  - e0197187
LID - 10.1371/journal.pone.0197187 [doi]
LID - e0197187
AB  - 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.
FAU - Meconi, Alicia
AU  - Meconi A
AD  - Division of Medical Sciences, University of Victoria, Victoria, British Columbia, 
      Canada.
FAU - Wortman, Ryan C
AU  - Wortman RC
AD  - Division of Medical Sciences, University of Victoria, Victoria, British Columbia, 
      Canada.
FAU - Wright, David K
AU  - Wright DK
AD  - The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, 
      Australia.
AD  - Department of Neuroscience, Monash University, Melbourne, Victoria, Australia.
FAU - Neale, Katie J
AU  - Neale KJ
AD  - Division of Medical Sciences, University of Victoria, Victoria, British Columbia, 
      Canada.
FAU - Clarkson, Melissa
AU  - Clarkson M
AD  - Division of Medical Sciences, University of Victoria, Victoria, British Columbia, 
      Canada.
FAU - Shultz, Sandy R
AU  - Shultz SR
AD  - Division of Medical Sciences, University of Victoria, Victoria, British Columbia, 
      Canada.
AD  - The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, 
      Australia.
AD  - Department of Neuroscience, Monash University, Melbourne, Victoria, Australia.
AD  - Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
FAU - Christie, Brian R
AU  - Christie BR
AUID- ORCID: 0000-0002-6830-0160
AD  - Division of Medical Sciences, University of Victoria, Victoria, British Columbia, 
      Canada.
AD  - Centre for Brain Health and Program in Neuroscience, University of British 
      Columbia, Vancouver, British Columbia, Canada.
AD  - Department of Cellular and Physiological Sciences, University of British 
      Columbia, Vancouver, British Columbia, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180508
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Animals
MH  - Brain Concussion/*physiopathology
MH  - Brain Injuries, Traumatic/*physiopathology
MH  - Cerebral Cortex/physiopathology
MH  - Disease Models, Animal
MH  - Female
MH  - Hippocampus/*physiopathology
MH  - Humans
MH  - Male
MH  - Memory Disorders/*physiopathology
MH  - Neurologic Examination
MH  - Rats
MH  - Spatial Memory/physiology
PMC - PMC5940222
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2018/05/09 06:00
MHDA- 2018/08/02 06:00
PMCR- 2018/05/08
CRDT- 2018/05/09 06:00
PHST- 2018/02/17 00:00 [received]
PHST- 2018/04/27 00:00 [accepted]
PHST- 2018/05/09 06:00 [entrez]
PHST- 2018/05/09 06:00 [pubmed]
PHST- 2018/08/02 06:00 [medline]
PHST- 2018/05/08 00:00 [pmc-release]
AID - PONE-D-18-05302 [pii]
AID - 10.1371/journal.pone.0197187 [doi]
PST - epublish
SO  - PLoS One. 2018 May 8;13(5):e0197187. doi: 10.1371/journal.pone.0197187. 
      eCollection 2018.