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Brain Inj. 2018;32(1):113-122. doi: 10.1080/02699052.2017.1380228. Epub 2017 Nov 20.

Repeated mild traumatic brain injury produces neuroinflammation, anxiety-like behaviour and impaired spatial memory in mice.

Author information

1
a Beth K and Stuart C. Yudofsky Division of Neuropsychiatry , Baylor College of Medicine , Houston , TX , USA.
2
b Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales , Universidad de Buenos Aires - CONICET , Buenos Aires , Argentina.
3
c Departments of Psychiatry , University of Iowa , Iowa City , IA , USA.
4
d Department of Veteran Affairs , Michael E DeBakey VA Medical Center , Houston TX , USA.
5
e Free Radical & Radiation Biology Program, Department of Radiation Oncology Holden Comprehensive Cancer Center , University of Iowa , Iowa City , IA , USA.
6
f Department of Neurosurgery , Baylor College of Medicine , Houston , TX , USA.
7
g Neurology , University of Iowa , Iowa City , IA , USA.
8
h Department of Neuroscience , Baylor College of Medicine , Houston , TX , USA.
9
i Department of Veterans Affairs , Carver College of Medicine, University of Iowa , Iowa City , IA , USA.
10
j Cornell Autism Research Program , Weill Cornell Medical College , New York , NY , USA.

Abstract

PRIMARY OBJECTIVE:

Repeated traumatic brain injuries (rmTBI) are frequently associated with debilitating neuropsychiatric conditions such as cognitive impairment, mood disorders, and post-traumatic stress disorder. We tested the hypothesis that repeated mild traumatic brain injury impairs spatial memory and enhances anxiety-like behaviour.

RESEARCH DESIGN:

We used a between groups design using single (smTBI) or repeated (rmTBI) controlled cranial closed skull impacts to mice, compared to a control group.

METHODS AND PROCEDURES:

We assessed the effects of smTBI and rmTBI using measures of motor performance (Rotarod Test [RT]), anxiety-like behaviour (Elevated Plus Maze [EPM] and Open Field [OF] tests), and spatial memory (Morris Water Maze [MWM]) within 12 days of the final injury. In separate groups of mice, astrocytosis and microglial activation were assessed 24 hours after the final injury using GFAP and IBA-1 immunohistochemistry.

MAIN OUTCOMES AND RESULTS:

RmTBI impaired spatial memory in the MWM and increased anxiety-like behaviour in the EPM and OFT. In addition, rmTBI elevated GFAP and IBA-1 immunohistochemistry throughout the mouse brain. RmTBI produced astrocytosis and microglial activation, and elicited impaired spatial memory and anxiety-like behaviour.

CONCLUSIONS:

rmTBI produces acute cognitive and anxiety-like disturbances associated with inflammatory changes in brain regions involved in spatial memory and anxiety.

KEYWORDS:

Animal model; anxiety; chronic traumatic encephalopathy; mild traumatic brain injury; spatial memory

PMID:
29156991
DOI:
10.1080/02699052.2017.1380228
[Indexed for MEDLINE]

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