Closed Traumatic Brain Injury Model in Sheep Mimicking High-Velocity, Closed Head Trauma in Humans

Abstract

To date, there are only a few, non-evidence based, cerebroprotective therapeutic strategies for treatment and, accordingly, for prevention of secondary brain injuries following severe closed head trauma. In order to develop new therapy strategies, existing realistic animal models need to be advanced. The objective is to bridge standardized small animal models and actual patient medical care, since the results of experimental small animal studies often cannot be transferred to brain-injured humans. For improved standardization of high-velocity trauma, new trauma devices for initiating closed traumatic brain injury in sheep were developed. The following new devices were tested: 1. An anatomically shaped rubber bolt with an integrated oscillation absorber for prevention of skull fractures; 2. Stationary mounting of the bolt to guarantee stable experimental conditions; 3. Varying degrees of trauma severity, i. e., mild and severe closed traumatic brain injury, using different cartridges; and 4. Trauma analysis via high-speed video recording. Peritraumatic measurements of intracranial pressure, brain tissue pH, brain tissue oxygen, and carbon dioxide pressure, as well as neurotransmitter concentrations were performed. Cerebral injuries were documented with magnetic resonance imaging and compared to neuropathological results. Due to the new trauma devices, skull fractures were prevented. The high-speed video recording documented a realistic trauma mechanism for a car accident. Enhancement of extracellular glutamate, aspartate, and gamma amino butyric acid concentrations began 60 min after the trauma. Magnetic resonance imaging and neuropathological results showed characteristic injury patterns of mild, and severe, closed traumatic brain injury. The severe, closed traumatic brain injury group showed diffuse axonal injuries, traumatic subarachnoid hemorrhage, and hemorrhagic contusions with inconsistent distribution among the animals. The model presented here achieves a gain in standardization of severe, closed traumatic brain injury by increasing approximation to reality. The still existent heterogeneity of brain pathology mimics brain changes observed in patients after high-energy trauma. This model seems to close the gap between experimental small animal models and clinical studies. However, further investigations are needed to evaluate if this model can be used for testing new therapeutic strategies for these patients.

Key words

closed traumatic brain injury - experimental animal model - magnetic resonance imaging - multiparametric cerebral monitoring - sheep

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