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A blast injury is a complex type of physical trauma resulting from the detonation of explosive compounds and has become an important issue due to the use of improvised explosive devices (IED) in current military conflicts. Blast-induced neurotrauma (BINT) is a major concern in contemporary military medicine and includes a variety of injuries that range from mild to lethal. Extreme forces and their complex propagation characterize BINT. Modern body protection and the development of armored military vehicles can be assumed to have changed the outcome of BINT. Primary blast injuries are caused by overpressure waves whereas secondary, tertiary, and quaternary blast injuries can have more varied origins such as the impact of fragments, abnormal movements, or heat. The characteristics of the blast wave can be assumed to be significantly different in open field detonations compared to explosions in a confined space, such an armored vehicle. Important parameters include peak pressure, duration, and shape of the pulse. Reflections from walls and armor can make the prediction of effects in individual cases very complex. Epidemiological data do not contain information of the comparative importance of the different blast mechanisms. It is therefore important to generate data in carefully designed animal models. Such models can be selective reproductions of a primary blast, penetrating injuries from fragments, acceleration movements, or combinations of such mechanisms. It is of crucial importance that the physical parameters of the employed models are well characterized so that the experiments can be reproduced in different laboratory settings. Ideally, pressure recordings should be calibrated by using the same equipment in several laboratories. With carefully designed models and thoroughly evaluated animal data it should be possible to achieve a translation of data between animal and clinical data. Imaging and computer simulation represent a possible link between experiments and studies of human cases. However, in order for mathematical simulations to be completely useful, the predictions will most likely have to be validated by detailed data from animal experiments. Some aspects of BINT can conceivably be studied in vitro. However, factors such as systemic response, brain edema, inflammation, vasospasm, or changes in synaptic transmission and behavior must be evaluated in experimental animals. Against this background, it is necessary that such animal experiments are carefully developed imitations of actual components in the blast injury. This paper describes and discusses examples of different designs of experimental models relevant to BINT.

A new in vivo animal model that produces diffuse brain injuries in sagittal plane rearward rotational acceleration has been developed. In this model, the skull of an anesthetized adult rat is tightly secured to a rotating bar. During trauma, the bar is impacted by a striker that causes the bar and the animal head to rotate rearward; the acceleration phase last 0.4 ms and is followed by a rotation at constant speed and a gentle deceleration when the bar makes contact with a padded stop. The total head angle change is less than 30°. By adjusting the air pressure in the rifle used to accelerate the striker, resulting rotational acceleration between 0.3 and 2.1 Mrad/s2 can be produced. Numerous combinations of trauma levels, post-trauma survival times, brain and serum retrieval, and tissue preparation techniques were adopted to characterize this new model. The trauma caused subdural bleedings in animals exposed to severe trauma. Staining brain tissue with β-Amyloid Precursor Protein antibodies and FD Neurosilver that detect degenerating axons revealed wide spread axonal injuries (AI) in the corpus callosum, the border between the corpus callosum and cortex and in tracts in the brain stem. The observed AIs were apparent only when the rotational acceleration level was moderate and above. On the contrary, only limited signs of contusion injuries were observed following trauma. Macrophage invasions, glial fibrillary acidic protein redistribution or hypertrophy, and blood brain barrier (BBB) changes were unusual. S100 serum analyses indicate that blood vessel and glia cell injuries occur following moderate levels of trauma despite the absence of obvious BBB injuries. We conclude that this rotational trauma model is capable of producing graded axonal injury, is repeatable and produces limited other types of traumatic brain injuries and as such is useful in the study of injury biomechanics, diagnostics, and treatment strategies following diffuse axonal injury.

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Mild traumatic brain injury (mTBI) is one of the most common neuronal insults and can lead to long-term disabilities. mTBI occurs when the head is exposed to a rapid acceleration-deceleration movement triggering axonal injuries. Our limited understanding of the underlying pathological changes makes it difficult to predict the outcome of mTBI. In this study we used a scalable rat model for rotational acceleration TBI, previously characterized for the threshold of axonal pathology. We have analyzed whether a TBI just above the defined threshold would induce any detectable behavioral changes and/or changes in serum biomarkers. The effect of injury on sensory motor functions, memory and anxiety were assessed by beam walking, radial arms maze and elevated plus maze at 3–7 days following TBI. The only behavioral deficits found were transient impairments in working and reference memory. Blood serum was analyzed at 1, 3, and 14 days after injury for changes in selected protein biomarkers. Serum levels of neurofilament heavy chain and Tau, as well as S100B and myelin basic protein showed significant increases in the injured animals at all time points. No signs of macroscopic injuries such as intracerebral hematomas or contusions were found. Amyloid precursor protein immunostaining indicated axonal injuries at all time points analyzed. In summary, this model mimics some of the key symptoms of mTBI, such as transient memory impairment, which is paralleled by an increase in serum biomarkers. Our findings suggest that serum biomarkers may be used to detect mTBI. The model provides a suitable foundation for further investigation of the underlying pathology of mTBI.