Controlled Cortical Impact in the Rat

Abstract

Traumatic brain injury (TBI) is a major cause of death and disability world-wide. Following initial injury, TBI patients can face long-term disability in the form of cognitive, physical, and psychological deficits, depending on the severity and location of injury. This results in an economic burden in the United States estimated to be $60 billion due to health-care costs and loss of productivity. TBI is a significant area of active research interest for both military and civilian medicine. Numerous pre-clinical animal models of TBI are used to characterize the anatomical and physiological pathways involved and to evaluate therapeutic interventions. Due to its flexibility and scalability, controlled cortical impact (CCI) is one of the most commonly used preclinical TBI models. This unit provides a basic CCI protocol performed in the rat. © 2017 by John Wiley & Sons, Inc.

Keywords: cortical controlled impact; rat; traumatic brain injury.

Figure 1

This is an example of a surgical log used to record peri-operative details as well as post-surgical recovery.

Figure 2

Representative images from critical portions of the controlled cortical impact procedure are shown. The rat’s head is positioned in the anesthetic nose cone and stereotactic apparatus so that the nose is towards the top of the page. A) Initial incision after clean up to expose skull; B) Initial scoring of skull for target area; C) Bone flap immediately prior to removal; D) Bone flap removed to expose intact cortex prior to impact; E) Impactor positioned and impactor tip retracted above target area of cortex; F) Cortex after impact. Note the different in color between (D) and this post-impact image, representing contusion below the intact dura. If the dura had ruptured, free blood would be hemorrhaging from the cortex, rather than be contained beneath the dura; G) Bone flap replaced; H) Bone flap sealed with dental acrylic; I) Interrupted sutures to close scalp incision.

Figure 3

Example of results from motor function assessments using longitudinal foot fault analysis after controlled cortical impact (CCI). For this experiment, three cohorts were followed, a CCI plus treatment group (CCI+Tx), a CCI plus treatment vehicle group (CCI+Vehicle), and an uninjured control group. Each cohort for this experiment contained 6 rats. The day indicates the time post-CCI. At early time points there are more foot faults per distance traveled observed in rats after CCI than in uninjured rats, and no statistically significant differences between the two treatment groups. Post-CCI and control rats are more similar one week after injury. For the example shown, statistical analysis was performed by one-way analysis of variance (ANOVA) with post-hoc Tukey analysis.

Figure 4

Examples from two rats (A–C, D–F) depicting of the evolution of the controlled cortical impact (CCI) lesion on in vivo MRI. The left side of the rat is towards the left-hand side of the page, in contrast to how human clinical MRI images are portrayed. (A,D) At two days post-injury, there is hyperintensity surrounding the area of impact and extending into the corpus callosum, indicative of tissue damage and edema. (B,E) At nine days post-injury, this edema has resolved but the area of injury is still visible. (C,F) By thirty days post-injury, there is some degree of tissue atrophy on the side of injury, as indicated by thinning of the cortex and enlargement of the lateral ventricle. The protocol was performed identically in both rats, but the rat depicted in A–C manifested less atrophy by 30 days than the rat shown in D–F. Even under the most controlled of circumstances, there can be variability in the appearance and response of individual rats to the CCI injury.