Controlled Cortical Impact Model

Excerpt

The use of in vivo (i.e., animal) models to study traumatic brain injury (TBI) is far from new; indeed since the late 1800s many models of brain injury have been employed for this purpose (Gennarelli et al., 1982; Govons et al., 1972; Nilsson, Pontén, and Voigt, 1977; Ommaya, Geller, and Parsons, 1971; Ommaya and Gennarelli, 1974; Rinder and Olsson, 1968; Sullivan et al., 1976; Denny-Brown and Russell, 1941; Kramer, 1896; Cannon, 1901; Parkinson, West, and Pathiraja, 1978). In the 1980s, Lighthall and his colleagues developed a pneumatic impactor for the purpose of modeling TBI in ferrets (Lighthall, 1988; Lighthall, Goshgarian, and Pinderski, 1990); this method is now referred to as controlled cortical impact (CCI). The control and reproducibility of CCI led Dixon and colleagues to adapt the model for use in rats (Dixon et al., 1991). Since its development, CCI has become one of the most common models of brain injury in animals and has been applied to numerous species. This chapter will familiarize the reader with the key aspects of CCI (e.g., species applied to; types of devices) the clinical features of brain injury replicated by this model, and considerations for researchers using CCI. It will also provide a standard protocol for pneumatic CCI in rats.

Controlled cortical impact allows for quantitative control over injury force and velocity as well as extent of tissue deformation; thus, it affords control over biomechanical parameters known to be associated with TBI. This independent control over injury parameters across a wide range of contact velocity contributes to the reliability and accuracy of controlled cortical impact (CCI) as a model of TBI. Depending on the goals of the research study, injury can be controlled to produce a range of injury magnitudes, allowing the researcher to produce gradable functional impairment, tissue damage, or both. A thorough review of the literature can provide preliminary guidance regarding how to set the injury parameters for the study. Beyond reviewing the literature, it is encouraged that researchers conduct pilot work to help them fine-tune the CCI parameters to best meet their research goals. Pilot work will also allow the researchers to test the machine and ensure that it is working properly and the velocity and dwell time is consistent with what is set.

Briefly, CCI consists of an anesthetized incision and craniectomy to gain access to the animal’s brain for injury induction in the form of deformation of brain tissue using a pneumatic or electromechanical CCI device. Although CCI is an invasive model of head trauma that requires neurosurgery, only one surgical procedure is needed as opposed to the two required when using the standard fluid percussion model of brain injury (Kline and Dixon, 2001). An additional strength of CCI is that it can be scaled to model TBI in different mammalian species ranging from small to large depending on the goals of the research and available facilities. Of the most common models of experimental brain injury, CCI has the broadest applicability across species and has been modified for use in: mice (Fox et al., 1998b; Lee et al., 2012; Smith et al., 1995; Wang et al., 2013), rats (Acosta et al., 2013; Dixon et al., 1991; Vonder Haar et al., 2013; Xing et al., 2012), swine (Costine et al., 2012; Manley et al., 2006; Friess et al., 2007, 2009a), and primates (King et al., 2010). None of the other common models of brain injury (e.g., fluid percussion, weight drop) been used across all the aforementioned animal species.