Controlled Cortical Impact Model for Traumatic Brain Injury

Summary

Traumatic brain injuries (TBIs) remain a serious health problem. Using the controlled cortical impact surgery model, research on the effects of TBI and possible treatment methods may be performed.

Abstract

Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.

Introduction

Traumatic brain injury (TBI) is defined as an alteration in brain function, or other evidence of brain pathology, caused by an external force¹. TBIs remain a serious health problem throughout the world, particularly in the United States. According to the Centers for Disease Control and Prevention, at least 1.7 million TBIs occur annually in the United States resulting in 30.5% of all injury-related deaths. In 2000, the direct medical costs and indirect costs of TBIs totaled an estimated $76.5 billion in the United States alone. Although technological and therapeutic advancements in preceding decades have improved the quality and length of life for those suf....

Protocol

Animal Care
Male C57 BL/6 mice were group-housed and kept in a 12/12 hr light/dark cycle with free to access to food and water ad libitum. The animals used in this protocol were 10-12 weeks old. All procedures were performed under protocols approved by Indiana University’s Animal Care and Use Committee.

1. Surgical Preparation

1. Anesthetize the mouse using a Ketamine/xylazine mixture (87.7 mg/ml Ketamine and 12.3 mg/ml Xylazine) and administer (1 ml/kg) via IP injection.
2. Shave the head of the mouse between the ears.
3. Apply a petroleum-based jelly to the eyes of the mouse ....

Results

The controlled cortical impact model produces TBIs ranging in severity from mild to severe. Post-impact the amount of cranial swelling, bleeding, and cranial distortion at the impact site will reveal the injury severity resulting from the speed and deformation depth parameters. Mild TBIs result in cranial swelling at the impact site and slight bleeding due to the limited dura breach. A moderate TBI exhibits cranial swelling and increased bleeding due to dura breach upon impaction (Figure 1). The differen.......

Discussion

The most critical steps for successfully generating consistent TBIs using an electronic magnet impact system to cause a CCI are: 1) stably fixing the mouse head in the stereotactic frame; 2) generating the same size of bone window between mice and removing the bone without damaging the dura under it during craniectomy; 3) correctly positioning the impact tip in the center of the open area and establishing the zero point before impacting.

A mouse head must be fixed in the stereotactic frame ver.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Povidone-iodine 7.5%	Purdue product L.P.		Surgical scrub
Cotton tipped applicators	Henry Schein	100-6015	Remove blood and debris
Scissor	Fine Science Tools	14084-08	Surgery
Forcept	Fine Science Tools	11293-00	Surgery
Hemostat	Fine Science Tools	13021-12	Surgery
Rechargeable Cordless Micro Drill	Stoelting	58610	Combine with Burrs for generating the bone window
Burrs for Micro Drill	Fine Science Tools	19007-05
Suture monofilament	Ethicon	G697	Suture
tert-Amyl alcohol	Sigma	152463-250ML	Making 2.5% Avertin
2,2,2-Tribromoethanol	Sigma	T48402-25G	Making 2.5% Avertin