Historical Review of the Fluid-Percussion TBI Model

Abstract

Traumatic brain injury (TBI) is a major health concern worldwide. Laboratory studies utilizing animal models of TBI are essential for addressing pathological mechanisms of brain injury and development of innovative treatments. Over the past 75 years, pioneering head injury researchers have devised and tested a number of fluid percussive methods to reproduce the concussive clinical syndrome in animals. The fluid-percussion brain injury technique has evolved from early investigations that applied a generalized loading of the brain to more recent computer-controlled systems. Of the many preclinical TBI models, the fluid-percussion technique is one of the most extensively characterized and widely used models. Some of the most important advances involved the development of the Stalhammer device to produce concussion in cats and the later characterization of this device for application in rodents. The goal of this historical review is to provide readers with an appreciation for the time and effort expended by the pioneering researchers who have led to today’s state of the art fluid-percussion animal models of TBI.

Modified device for fluid percussion injury in rodents

“…However, besides the surgical difficulty in drilling the fragile cranium of rodents (Lyeth, 2016;Marklund & Hillered, 2011), the FP device also poses certain technical challenges in preparation of TBI model (Kabadi et al, 2010;Lyeth, 2016;Marklund, 2016). For example, accurate leveling and releasing of the pendulum are essential for achieving the constant striking force.…”

Animal Models of Post-Traumatic Epilepsy

“…FPI model demonstrates increased seizures susceptibility and reproduces the histopathology associated with traumatic brain injury, including, diffuse white matter injury of varying severity, a focal contusion within the cerebral cortex with accompanying petechial or intraparenchymal hemorrhage, cerebral edema, progressive gray matter damage and white matter tissue tears suggesting a high construct validity [22,25]. Furthermore, FPI model demonstrates persistent neuromotor and cognitive deficits up to one year following severe FPI with the associated temporal pattern of cellular death that recapitulate what is seen in traumatic brain injury patient [26,27].…”

Large animal models of traumatic brain injury

“…This can be varied by altering the angular height from which the pendulum weight is dropped. Typically, direct brain deformation results in focal tissue damage, including neuronal loss, increased blood‐brain barrier (BBB) permeability, and edema, as well as some petechial hemorrhage under the site of the craniotomy (Lyeth, ). Changing the site of the craniectomy from a midline to a lateral position alters the site of maximal tissue injury as well as introducing a shearing component to the injury (McIntosh et al, ; Vink, Mullins, Temple, Bao, & Faden, ).…”

“…In large part, this is because rodents offer a low‐cost option with readily available outcome measures and a considerable database of normative data that has been carefully developed and collated over many years. Interested readers can find details of these models, and how they reproduce various aspects of human outcomes after TBI, in some excellent reviews that have recently been published and need not be reiterated here (Bondi et al, ; Cernak, ; Lyeth, ; Osier & Dixon, ). However, rodents were not always the animal species of choice, with several species of larger animals being more commonly used in studies up until the 1980s.…”