A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

Summary

Athletes absorb several hundred mild traumatic brain injuries (mTBI)/concussions every year; however, the consequence of these on the brain is poorly understood. Therefore, an animal model of single and repetitive mTBI that consistently replicates clinically relevant symptoms provides the means to advance the study of mTBI and concussion.

Abstract

Mild Traumatic Brain Injury (mTBI) can result in the acute loss of brain function, including a period of confusion, a loss of consciousness (LOC), focal neurological deficits and even amnesia. Athletes participating in contact sports are at high risk of exposure to large number of mTBIs. In terms of the level of injury in a sporting athlete, a mTBI is defined as a mild injury that does not cause gross pathological changes, but does cause short-term neurological deficits that are spontaneously resolved. Despite previous attempts to model mTBI in mice and rats, many have reported gross adverse effects including skull fractures, intracerebral bleeding, axonal injury and neuronal cell death. Herein, we describe our highly reproducible animal model of mTBI that reproduces clinically relevant symptoms. This model uses a custom made pneumatic impactor device to deliver a closed-head trauma. This impact is made under precise velocity and deformation parameters, creating a reliable and reproducible model to examine the mechanisms that contribute to effects of single or repetitive concussive mTBI.

Introduction

Traumatic Brain Injury (TBI) is defined as a head injury sustained from an external physical force, resulting in the disruption of normal brain function. It represents a significant socio-economic and public health burden, with the Center for Disease Control and Prevention 2015 Report to Congress estimating that 2.5 million Americans sustain a TBI every year. This impacts not only the patient's quality of life, but also places an extremely high economic cost on the community, currently estimated at $76.5 billion annually. The amount of actual brain damage conveyed and the acute phase symptomologies is what defines mild, moderate and severe TBI.

Protocol

These studies were performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes Health. The protocol was approved by the Institutional Animal Care and Use Committee at Georgetown University. Mice were housed in a temperature controlled animal facility and were kept on a 12 h light/12 h dark cycle. Food and water were available ad libitum.

1. Preparation of the mTBI Apparatus

NOTE: The mTBI apparatus includes a data acquisition (DAQ) box to control impact parameters, a high-velocity pneumatic impactor to perform the impaction, and....

Results

The use of this novel mTBI device allows for single and repetitive mild head injuries without risk of skull fracture or structural brain damage. The model uses a custom made pneumatic Teflon impactor device to deliver a closed head mechanical energy impact. The impact is made under precise velocity and deformation parameters, creating a reliable and reproducible model to examine the mechanisms that contribute to effects of single or repetitive concussive mTBI (Figure .......

Discussion

In humans, mTBI is characterized by a functional impairment in the absence of structural injury. This can occur with, or without, a loss of consciousness¹. Exposure to repeat concussions is currently thought to underlie the development and/or progression of neurodegenerative diseases such as CTE⁴. It is well documented that CTE is commonly found in boxers and football players and although exposure to repeat concussions (including those that do not result in a loss of consci.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Powerlab 8SP data acquisition (DAQ) control box	(AD instruments)
VIP 3000 calibrated vaporizer	Matrx
Isoflurane	Henry Schein Animal Health	29405
Oxygen			Commercially available
Compressed Air			Commercially available
Masking Tape			Commercially available
Stop Watch	Fisher Scientific	02-261-840
C57 Bl/6 Mice	Jackson Laboratories
Digital Scale and weigh container	Fisher Scientific	20031
anti-Iba1 antibody	Wako	019-19741
HRP labelled secondary	Jackson Immunoresearch	111-035-003