A Repetitive Concussive Head Injury Model in Mice

Summary

Concussion presents the most common type of traumatic brain injury. Therefore, a repetitive concussive animal model, which replicates the important features of an injury in patients, may provide a means to study concussion in a rigorous, controlled, and efficient manner.

Abstract

Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of knowledge on the injury and its effects. To develop a better understanding of concussions, animals are often used because they provide a controlled, rigorous, and efficient model. Studies have adapted traditional animal models to perform mTBI to stimulate mild injury severity by changing the injury parameters. These models have been used because they can produce morphologically similar brain injuries to the clinical condition and provide a spectrum of injury severities. However, they are limited in their ability to present the identical features of injuries in patients. Using a traditional impact system, a repetitive concussive injury (rCHI) model can induce mild to moderate human-like concussion. The injury degree can be determined by measuring the period of loss of consciousness (LOC) with a sign of a transient termination of breathing. The rCHI model is beneficial to use for its accuracy and simplicity in determining mTBI effects and potential treatments.

Introduction

Concussion, also called mild traumatic brain injury (mTBI), is the most frequent occurrence of traumatic brain injury (TBI) and affects millions of people in United States. Concussions can be tricky to diagnose and there is no specific cure for concussion. There is a growing recognition and some evidence that mild mechanical trauma resulting from sports injuries, military combat, and other physically engaging pursuits may have cumulative and chronic neurological consequences^1,2. However, there is still a lack of knowledge regarding concussions and their effects. Current methodology restricts the studies of pathology and treatment in humans since only neurol....

Protocol

All procedures were performed under protocols #201207692 approved by the Institutional Animal Care and Use Committee of University of Florida and in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

1. Animal Care

1. Use 3–4-month-old male C57BL/6J mice. Provide bedding, nesting material, food, and water ad libitum. Keep the mice in ambient temperatures controlled at 20 - 22 °C with constant 12-hr light/12-hr dark cycles.

2. Pre-impaction Preparation

1. Attach a custom-made silicone rubber-coated metal tip to an electro....

Results

In this model (Figure 1 A-C), there were brief periods of gasping and shallow respirations. A loss of consciousness (unconscious) is defined as a decrease in the breathing rate or transient termination of breathing before resuming a normal respiration. An impact on the center of the head caused short-term unconsciousness (7.5 ± 4.7, 7.8 ± 5.5, 10.2 ± 8.8, 9.5 ± 8.0 sec at each impact separately, Figure 1D). Mouse brains showed normal m.......

Discussion

To mimic brain injuries morphologically similar to the clinical condition, post-concussion symptoms are expected. Post-concussion symptoms generally include headaches, dizziness, vertigo, fatigue, memory and sleeping problems, trouble concentrating as well as anxiety, and depressed mood. Since somatic symptoms may not yet be measurable in animal models, the changes of motor and cognitive function and emotional behavior are used as criteria for rationally evaluating concussion in animal models. In a previous reported stud.......

Materials

Name	Company	Catalog Number	Comments
anesthesia machine	Eagle Eye Anesthesia, Inc	Model 150	anesthesia
Electromagnetic Impactor	LeicaBiosystems	Impact One Stereotaxic Impactor	perform impaction
Digital Stereotaxic instrument	LeicaBiosystems	39462501	mount mouse and positioning tips
Sicilone rubber-coated metal tip	Precision Tool & Engineering, Gainesvill FL	custom-made	impact tip
Lithium Ion All-in-One Trimmer	WAHL Home Products	9854-600	shave mouse hair
paper clips	custom-made		probe tip
Cotton tipped applicators	MEDLINE	MDS202055	scrub head with saline
Tissue Tek O.C.T.	ASKURA FINETEK USA INC	4583	tissue embedding
anti-GFAP	Dako	CA93013	antibody for IHC
anti Ferritin	Sigma	F6136	antibody for IHC
VECTASTAIN Elite ABC  kit	Vector laboratories	PK-6100	IHC detection system
Permount Mounting Medium	Fisher Scientific	SP15-100
Aperio XT ScanScope scanner	Leica Microsystems Inc,		slides scanning
Leica AutoStainer XL	Leica the pathology Company	ST2010	H&E staining
DAB	sigma	D3939	IHC detection system