Characterization of a New Rat Model of Penetrating Ballistic Brain Injury

Abstract

Penetrating brain injury (PBI) is a leading cause of mortality and morbidity in modern warfare and accounts for a significant number of traumatic brain injuries worldwide. Here we characterize the pathophysiology of a new rat model of PBI that simulates the large temporary cavity caused by energy dissipation from a penetrating bullet round. Male Sprague-Dawley rats (250-300 g) were subjected to a simulated ballistic wound to the right frontal hemisphere implemented by an inflatable penetrating probe. Three levels of injury severity were compared to control animals. Neurological and physiological outcome was assessed over a 3-day recovery period and brain tissue collected at 72 h for histopathological evaluation. Brain-injured regions included the ipsilateral frontal cortex and striatum with volumetric increases in intracranial hemorrhage (5-18 mm3) and lesion size (9-86 mm3) related to severity. Similarly, hemispheric swelling increased (3-14%) following PBI, associated with a significant rise in intracranial pressure. Astrogliosis was present in regions adjacent to the core-injury along with microglial and leukocyte infiltration. Injury remote to the lesion was observed in the cerebral peduncle that may have accounted, in part, for observed neurological deficits. Neurological and balance beam testing revealed sensorimotor deficits that persisted through 72 h. Severe electroencephalographic disturbances included the occurrence of cortical spreading depression, slow-waves, and brain seizure activity. In conclusion, this rat PBI model replicates diverse, salient features of clinical PBI pathology, generates reproducible and quantifiable measures of outcome, and is scalable by injury severity, rendering it an attractive vehicle for experimental brain trauma research.

Systems Biology Approaches for Discovering Biomarkers for Traumatic Brain Injury

“…In vivo microarray studies generally used either fluid percussion injury (FPI), in which injury is produced by the impact of a pendulum onto a fluid reservoir, or controlled cortical impact (CCI), in which a rigid, computer-controlled, pneumatically driven impactor strikes the dural surface. 59,60 The studies of Natale and colleagues 53 and Babikian and colleagues 54 have provided rich microarray data sets covering different animals (mouse and rat), models of TBI (FPI and CCI), severity levels (moderate to severe), and brain tissues (cortex and hippocampus) collected at distinct time points. Natale and colleagues, using an FPI rat model and a CCI mouse model, identified 82 genes differentially expressed in FIG.…”

RETRACTED: Hyperelastic mechanical behavior of rat brain infected by Plasmodium berghei ANKA – Experimental testing and constitutive modeling

“…A biomaterial can potentially be used to fill the cavity in the brain and deliver pharmacological or cellular therapeutic agents. While an existing animal model (Williams et al, 2005) offers the potential to investigate this treatment strategy, it is important to first identify biomaterials with appropriate mechanical characteristics. Finally, the hyperelastic properties of brain tissue may have many uses in the research areas that need accurate mechanical information such as in silico brain models used for surgery or injury simulation, surgical simulators that have many benefits to both medical teaching institutes and neurosurgery residents.…”

Role of Cortical Spreading Depressions for Secondary Brain Damage after Traumatic Brain Injury in Mice

“…There are different studies demonstrating that spreading depressions occur after experimental TBI. Cortical spreading depression-like DC shifts could be detected after penetrating ballistic brain injury (Williams et al, 2005), fluid percussion injury (Rogatsky et al, 2003), and cortical cold injury (Hermann et al, 1999;Trabold et al, 2006). Gradually, it has become clear that posttraumatic spreading depressions occur also in humans (Mayevsky et al, 1996;Strong et al, 2002;Parkin et al, 2005;Fabricius et al, 2006).…”