Blast overpressure induced axonal injury changes in rat brainstem and spinal cord

Introduction: Blast induced neurotrauma has been the signature wound in returning soldiers from the ongoing wars in Iraq and Afghanistan. Of importance is understanding the pathomechansim(s) of blast overpressure (OP) induced axonal injury. Although several recent animal models of blast injury indicate the neuronal and axonal injury in various brain regions, animal studies related to axonal injury in the white matter (WM) tracts of cervical spinal cord are limited. Objective: The purpose of this study was to assess the extent of axonal injury in WM tracts of cervical spinal cord in male Sprague Dawley rats subjected to a single insult of blast OP. Materials and Methods: Sagittal brainstem sections and horizontal cervical spinal cord sections from blast and sham animals were stained by neurofilament light (NF-L) chain and beta amyloid precursor protein immunocytochemistry and observed for axonal injury changes. Results: Observations from this preliminary study demonstrate axonal injury changes in the form of prominent swellings, retraction bulbs, and putative signs of membrane disruptions in the brainstem and cervical spinal cord WM tracts of rats subjected to blast OP. Conclusions: Prominent axonal injury changes following the blast OP exposure in brainstem and cervical spinal WM tracts underscores the need for careful evaluation of blast induced injury changes and associated symptoms. NF-L immunocytochemistry can be considered as an additional tool to assess the blast OP induced axonal injury

Biomechanical Responses of the Brain in Swine Subject to Free-Field Blasts

Blast-induced traumatic brain injury (bTBI) is a signature wound of modern warfare. The current incomplete understanding of its injury mechanism impedes the development of strategies for effective protection of bTBI. Despite a considerable amount of experimental animal studies focused on the evaluation of brain neurotrauma caused by blast exposure, there is very limited knowledge on the biomechanical responses of the gyrenecephalic brain subjected to primary free-field blast waves imposed in vivo. This study aims to evaluate the external and internal mechanical responses of the brain against different levels of blast loading with Yucatan swine in free field. The incident overpressure (IOP) was generated using 3.6 kg of C4 charge placed at three standoff distances from the swine. Five swine were exposed to a total of 19 blasts. The three average peak IOP pressure levels in this study were 148.8, 278.9, and 409.2 kPa as measured by a pencil probe. The duration of the first positive wave was in the range of 2.1 - 3 ms. Pressure changes in the brain and head kinematics were recorded with intracranial pressure (ICP) sensors, linear accelerometers and angular rate sensors. The corresponding average peak ICPs were in the range of 79-143, 210-281, and 311-414 kPa designated as low, medium, and high blast level, respectively. Peak head linear accelerations were in the range of 120-412 g. A positive correlation between IOP and its corresponding biomechanical responses of the brain was also observed. This experimental data can be used to validate computer models of bTBI

Time course of blast-induced injury in the rat auditory cortex

<div><p>Blast exposure is an increasingly significant health hazard and can have a range of debilitating effects, including auditory dysfunction and traumatic brain injury. To assist in the development of effective treatments, a greater understanding of the mechanisms of blast-induced auditory damage and dysfunction, especially in the central nervous system, is critical. To elucidate this area, we subjected rats to a unilateral blast exposure at 22 psi, measured their auditory brainstem responses (ABRs), and histologically processed their brains at 1 day, 1 month, and 3-month survival time points. The left and right auditory cortices was assessed for astrocytic reactivity and axonal degenerative changes using glial fibrillary acidic protein immunoreactivity and a silver impregnation technique, respectively. Although only unilateral hearing loss was induced, astrocytosis was bilaterally elevated at 1 month post-blast exposure compared to shams, and showed a positive trend of elevation at 3 months post-blast. Axonal degeneration, on the other hand, appeared to be more robust at 1 day and 3 months post-blast. Interestingly, while ABR threshold shifts recovered by the 1 and 3-month time-points, a positive correlation was observed between rats’ astrocyte counts at 1 month post-blast and their threshold shifts at 1 day post-blast. Taken together, our findings suggest that central auditory damage may have occurred due to biomechanical forces from the blast shockwave, and that different indicators/types of damage may manifest over different timelines.</p></div

Correlation between post-blast day 1 ABR thresholds and averaged bilateral astrocyte counts of the 1-month group.

<p>A significant positive correlation was observed between ABR thresholds and astrocyte counts (p = 0.04), suggesting a putative relationship between initial hearing loss and later-manifesting central auditory damage.</p

Auditory brainstem response thresholds in blast- and sham-exposed rats show temporary, blast-induced threshold elevations.

<p>For the 1 day post-blast group (1 D PB), significant threshold shifts were observed across clicks and all tone-burst frequencies in the blast-exposed ear (left ear). For the 1- and 3-month post-blast groups (1 Mo PB and 3 Mo PB), however, thresholds were similar to those of sham-exposed rats. There were no significant threshold shifts in the protected ear (right ear) following blast exposure at any time point. Error bars represent standard error of the mean.</p

Neuronal Injury and Glial Changes Are Hallmarks of Open Field Blast Exposure in Swine Frontal Lobe

<div><p>With the rapid increase in the number of blast induced traumatic brain injuries and associated neuropsychological consequences in veterans returning from the operations in Iraq and Afghanistan, the need to better understand the neuropathological sequelae following exposure to an open field blast exposure is still critical. Although a large body of experimental studies have attempted to address these pathological changes using shock tube models of blast injury, studies directed at understanding changes in a gyrencephalic brain exposed to a true open field blast are limited and thus forms the focus of this study. Anesthetized, male Yucatan swine were subjected to forward facing medium blast overpressure (peak side on overpressure 224–332 kPa; n = 7) or high blast overpressure (peak side on overpressure 350–403 kPa; n = 5) by detonating 3.6 kg of composition-4 charge. Sham animals (n = 5) were subjected to all the conditions without blast exposure. After a 3-day survival period, the brain was harvested and sections from the frontal lobes were processed for histological assessment of neuronal injury and glial reactivity changes. Significant neuronal injury in the form of beta amyloid precursor protein immunoreactive zones in the gray and white matter was observed in the frontal lobe sections from both the blast exposure groups. A significant increase in the number of astrocytes and microglia was also observed in the blast exposed sections compared to sham sections. We postulate that the observed acute injury changes may progress to chronic periods after blast and may contribute to short and long-term neuronal degeneration and glial mediated inflammation.</p></div