Animal models of traumatic brain injury

Abstract

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity both in civilian life and on the battlefield worldwide. Survivors of TBI frequently experience long-term disabling changes in cognition, sensorimotor function and personality. Over the past three decades, animal models have been developed to replicate the various aspects of human TBI, to better understand the underlying pathophysiology and to explore potential treatments. Nevertheless, promising neuroprotective drugs that were identified as being effective in animal TBI models have all failed in Phase II or Phase III clinical trials. This failure in clinical translation of preclinical studies highlights a compelling need to revisit the current status of animal models of TBI and therapeutic strategies.

Figure 1. Experimental set ups for the animal models of traumatic brain injury

a ∣ The fluid percussion injury (FPI) device uses rapid injection of a fluid pulse into the epidural space. b ∣ The controlled cortical impact (CCI) model uses an air or electromagnetic driven piston to penetrate the brain at a known distance and velocity. c ∣ The penetrating ballistic-like brain injury (PBBI) involves the transmission of projectiles with high energy of a metal rod or expansion of the probe’s elastic balloon. d ∣ In the Feeney weight-drop model, a free weight is released directly onto the exposed dura. e ∣ In the Marmarou weight-drop model, a metal disk is placed over the skull to prevent bone fracture. f ∣ The blast brain injury caused by primary injury of blast or other mechanisms, e.g., thoracic effect. Panels a,b,d,e are modified, with permission, from REF. [54]© 2003 Mary Ann Liebert, Inc. Publishers. Panel c is modified, with permission, from REF [55]© 2007 Mary Ann Liebert, Inc. Publishers.