Periventricular White Matter Alterations From Explosive Blast in a Large Animal Model: Mild Traumatic Brain Injury or "Subconcussive" Injury?

The neuropathology of mild traumatic brain injury in humans resulting from exposure to explosive blast is poorly understood as this condition is rarely fatal. A large animal model may better reflect the injury patterns in humans. We investigated the effect of explosive blasts on the constrained head minimizing the effects of whole head motion. Anesthetized Yucatan minipigs, with body and head restrained, were placed in a 3-walled test structure and exposed to 1, 2, or 3 explosive blast shock waves of the same intensity. Axonal injury was studied 3 weeks to 8 months postblast using ß-amyloid precursor protein immunohistochemistry. Injury was confined to the periventricular white matter as early as 3-5 weeks after exposure to a single blast. The pattern was also present at 8 months postblast. Animals exposed to 2 and 3 blasts had more axonal injury than those exposed to a single blast. Although such increases in axonal injury may relate to the longer postblast survival time, it may also be due to the increased number of blast exposures. It is possible that the injury observed is due to a condition akin to mild traumatic brain injury or subconcussive injury in humans, and that periventricular injury may have neuropsychiatric implications.

Neuronal and glial changes in the brain resulting from explosive blast in an experimental model.

Mild traumatic brain injury (mTBI) is the signature injury in warfighters exposed to explosive blasts. The pathology underlying mTBI is poorly understood, as this condition is rarely fatal and thus postmortem brains are difficult to obtain for neuropathological studies. Here we report on studies of an experimental model with a gyrencephalic brain that is exposed to single and multiple explosive blast pressure waves. To determine injuries to the brain resulting from the primary blast, experimental conditions were controlled to eliminate any secondary or tertiary injury from blasts. We found small but significant levels of neuronal loss in the hippocampus, a brain area that is important for cognitive functions. Furthermore, neuronal loss increased with multiple blasts and the degree of neuronal injury worsened with time post-blast. This is consistent with our findings in the blast-exposed human brain based on magnetic resonance spectroscopic imaging. The studies on this experimental model thus confirm what has been presumed to be the case with the warfighter, namely that exposure to multiple blasts causes increased brain injury. Additionally, as in other studies of both explosive blast as well as closed head mTBI, we found astrocyte activation. Activated microglia were also prominent in white matter tracts, particularly in animals exposed to multiple blasts and at long post-blast intervals, even though injured axons (i.e. ß-APP positive) were not found in these areas. Microglial activation appears to be a delayed response, though whether they may contribute to inflammation related injury mechanism at even longer post-blast times than we tested here, remains to be explored. Petechial hemorrhages or other gross signs of vascular injury were not observed in our study. These findings confirm the development of neuropathological changes due to blast exposure. The activation of astrocytes and microglia, cell types potentially involved in inflammatory processes, suggest an important area for future study.

Neuropathology of traumatic brain injury: comparison of penetrating, nonpenetrating direct impact and explosive blast etiologies.

The neuropathology of traumatic brain injury (TBI) from various causes in humans is not as yet fully understood. The authors review and compare the known neuropathology in humans with severe, moderate, and mild TBI (mTBI) from nonpenetrating closed head injury (CHI) from blunt impacts and explosive blasts, as well as penetrating head injury (PHI). Penetrating head injury and CHI that are moderate to severe are more likely than mTBI to cause gross disruption of the cerebral vasculature. Axonal injury is classically exhibited as diffuse axonal injury (DAI) in severe to moderate CHI. Diffuse axonal injury is also prevalent in PHI. It is less so in mTBI. There may be a unique pattern of periventricular axonal injury in explosive blast mTBI. Neuronal injury is more prevalent in PHI and moderate to severe CHI than mTBI. Astrocyte and microglial activation and proliferation are found in all forms of animal TBI models and in severe to moderate TBI in humans. Their activation in mTBI in the human brain has not yet been studied.

Concussive brain injury from explosive blast.

OBJECTIVE: Explosive blast mild traumatic brain injury (mTBI) is associated with a variety of symptoms including memory impairment and posttraumatic stress disorder (PTSD). Explosive shock waves can cause hippocampal injury in a large animal model. We recently reported a method for detecting brain injury in soldiers with explosive blast mTBI using magnetic resonance spectroscopic imaging (MRSI). This method is applied in the study of veterans exposed to blast. METHODS: The hippocampus of 25 veterans with explosive blast mTBI, 20 controls, and 12 subjects with PTSD but without exposure to explosive blast were studied using MRSI at 7 Tesla. Psychiatric and cognitive assessments were administered to characterize the neuropsychiatric deficits and compare with findings from MRSI. RESULTS: Significant reductions in the ratio of N-acetyl aspartate to choline (NAA/Ch) and N-acetyl aspartate to creatine (NAA/Cr) (P < 0.05) were found in the anterior portions of the hippocampus with explosive blast mTBI in comparison to control subjects and were more pronounced in the right hippocampus, which was 15% smaller in volume (P < 0.05). Decreased NAA/Ch and NAA/Cr were not influenced by comorbidities - PTSD, depression, or anxiety. Subjects with PTSD without blast had lesser injury, which tended to be in the posterior hippocampus. Explosive blast mTBI subjects had a reduction in visual memory compared to PTSD without blast. INTERPRETATION: The region of the hippocampus injured differentiates explosive blast mTBI from PTSD. MRSI is quite sensitive in detecting and localizing regions of neuronal injury from explosive blast associated with memory impairment.

Shaken baby syndrome: a biomechanics analysis of injury mechanisms.

Traumatic infant shaking has been associated with the shaken baby syndrome (SBS) diagnosis without verification of the operative mechanisms of injury. Intensities for SBS have been expressed only in qualitative, unsubstantiated terms usually referring to acceleration/deceleration rotational injury and relating to falls from great heights onto hard surfaces or from severe motor vehicle crashes. We conducted an injury biomechanics analysis of the reported SBS levels of rotational velocity and acceleration of the head for their injury effects on the infant head-neck. Resulting forces were compared with experimental data on the structural failure limits of the cervical spine in several animal models as well as human neonate cadaver models. We have determined that an infant head subjected to the levels of rotational velocity and acceleration called for in the SBS literature, would experience forces on the infant neck far exceeding the limits for structural failure of the cervical spine. Furthermore, shaking cervical spine injury can occur at much lower levels of head velocity and acceleration than those reported for the SBS. These findings are consistent with the physical laws of injury biomechanics as well as our collective understanding of the fragile infant cervical spine from (1) clinical obstetric experience, (2) automotive medicine and crash safety experience, and (3) common parental experience. The findings are not, however, consistent with the current clinical SBS experience and are in stark contradiction with the reported rarity of cervical spine injury in children diagnosed with SBS. In light of the implications of these findings on child protection and their social and medico-legal significance, a re-evaluation of the current diagnostic criteria for the SBS and its application is suggested.

Bone mineral density correlates with fracture load in experimental side impacts of the pelvis.

Pelvic fractures resulting from automotive side impacts are associated with high mortality and morbidity, as well as substantial economic costs. Previous experimental studies have produced varying results regarding the tolerance of the pelvis to lateral force and compression. While bone mineral density (BMD) has been shown to correlate with fracture loads in the proximal femur, no such correlation has been established for the pelvis. Presently, we studied the relationships between total hip BMD and impact response parameters in lateral impacts of twelve isolated human pelves. The results indicated that total hip BMD significantly correlated with fracture force, Fmax, and maximum ring compression, Cmax, of the fractured pelves. These findings are evidence that BMD may be useful in assessing the risk of pelvic fracture in automotive side impacts. Poor correlation was observed between total hip BMD and maximum viscous response, (VC)max, energy at fracture, Epeak, and time to fracture, tpeak. Mean Fmax and calculated tolerances for Cmax and (VC)max were lower than those established in previous studies using full cadavers, likely a result of our removal of soft tissues from the pelves prior to impact.