Development of a Minipig Model of BINT From Blast Exposure Using a Repeatable Mobile Shock Expansion Tube.

Introduction: The Office of Naval Research (ONR) sponsored the Blast Load Assessment Sense and Test (BLAST) program to provide an approach to operationally relevant monitoring and analysis of blast exposure for optimization of service member performance and health. Of critical importance in this effort was the development of a standardized methodology for preclinical large animal studies that can reliably produce outcome measures that cannot be measured in human studies to support science-based guidelines. The primary advantage of this approach is that, because animal studies report physiological measures that correlate with human neuropathology, these data can be used to evaluate potential risks to service members by accounting for the anatomical and physiological differences between humans and large animal models.

The Application of Machine Learning to Identify Large Animal Blast Exposure Thresholds.

Introduction: The Office of Naval Research sponsored the Blast Load Assessment Sense and Test program to develop a rapid, in-field solution that could be used by team leaders, commanders, and medical personnel to make science-based stand-down decisions for service members exposed to blast overpressure. Toward this goal, the authors propose an ensemble approach based on machine learning (ML) methods to derive a threshold surface for potential neurological deficits that encompasses the intensity of the blast events, the number of exposures, and the period over which the exposures occurred. Because of collection challenges presented by human subjects, the authors utilized data representing a comprehensive set of measures, including structural, behavioral, and cellular changes, from preclinical large animal studies on minipig models.

Evaluation of a Field-Ready Neurofunctional Assessment Tool for Use in a Military Environment.

Introduction: The Office of Naval Research sponsored the Blast Load Assessment Sense and Test (BLAST) program to develop a rapid, in-field solution that could be used by team leaders, commanders, and medical personnel to provide a standardized approach to operationally relevant monitoring and analysis of service members exposed to single or repeated low-level blast. A critical piece of the BLAST team's solution was the development of the Brain Gauge technology which includes a cognitive assessment device that measures neurofunctional changes by testing sensory perceptions and a suite of mathematical algorithms that analyze the results of the test. The most recent versions of the technology are easily portable; the device is in the size and shape of a computer mouse.

Methodological Problems With Online Concussion Testing.

Reaction time testing is widely used in online computerized concussion assessments, and most concussion studies utilizing the metric have demonstrated varying degrees of difference between concussed and non-concussed individuals. The problem with most of these online concussion assessments is that they predominantly rely on consumer grade technology. Typical administration of these reaction time tests involves presenting a visual stimulus on a computer monitor and prompting the test subject to respond as quickly as possible via keypad or computer mouse.

Noninvasive, In-pen Approach Test for Laboratory-housed Pigs.

Traumatic brain injury (TBI) incidences have increased in both civilian and military populations, and many researchers are adopting a porcine model for TBI. Unlike rodent models for TBI, there are few behavioral tests that have been standardized. A larger animal requires more invasive handling in test areas than rodents, which potentially adds stress and variation to the animals' responses.

Quantification of Mild Traumatic Brain Injury via Cortical Metrics: Analytical Methods.

Mild traumatic brain injuries are difficult to diagnose or assess with commonly used diagnostic methods. However, the functional state of cerebral cortical networks can be rapidly and effectively probed by measuring tactile-based sensory percepts (called cortical metrics), which are designed to exercise various components of cortical machinery. In this study, such cortical metrics were obtained from 52 college students before and after they experienced sports-related concussions by delivering vibrotactile stimuli to the index and middle fingertips.

Inosine enhances axon sprouting and motor recovery after spinal cord injury.

Although corticospinal tract axons cannot regenerate long distances after spinal cord injury, they are able to sprout collateral branches rostral to an injury site that can help form compensatory circuits in cases of incomplete lesions. We show here that inosine enhances the formation of compensatory circuits after a dorsal hemisection of the thoracic spinal cord in mature rats and improves coordinated limb use. Inosine is a naturally occurring metabolite of adenosine that crosses the cell membrane and, in neurons, activates Mst3b, a protein kinase that is part of a signal transduction pathway that regulates axon outgrowth.

GGF2 (Nrg1-β3) treatment enhances NG2+ cell response and improves functional recovery after spinal cord injury.

The adult spinal cord contains a pool of endogenous glial precursor cells, which spontaneously respond to spinal cord injury (SCI) with increased proliferation. These include oligodendrocyte precursor cells that express the NG2 proteoglycan and can differentiate into mature oligodendrocytes. Thus, a potential approach for SCI treatment is to enhance the proliferation and differentiation of these cells to yield more functional mature glia and improve remyelination of surviving axons.

Inosine augments the effects of a Nogo receptor blocker and of environmental enrichment to restore skilled forelimb use after stroke.

Stroke is the leading cause of disability in much of the world, with few treatment options available. Following unilateral stroke in rats, inosine, a naturally occurring purine nucleoside, stimulates the growth of projections from the undamaged hemisphere into denervated areas of the spinal cord and improves skilled use of the impaired forelimb. Inosine augments neurons' intrinsic growth potential by activating Mst3b, a component of the signal transduction pathway through which trophic factors regulate axon outgrowth.

Inosine alters gene expression and axonal projections in neurons contralateral to a cortical infarct and improves skilled use of the impaired limb.

Recovery after stroke and other types of brain injury is restricted in part by the limited ability of undamaged neurons to form compensatory connections. Inosine, a naturally occurring purine nucleoside, stimulates neurons to extend axons in culture and, in vivo, enhances the ability of undamaged neurons to form axon collaterals after brain damage. The molecular changes induced by inosine are unknown, as is the ability of inosine to restore complex functions associated with a specific cortical area.

Increased growth factor expression and cell proliferation after contusive spinal cord injury.

The damage caused by traumatic central nervous system (CNS) injury can be divided into two phases: primary and secondary. The initial injury destroys many of the local neurons and glia and triggers secondary mechanisms that result in further cell loss. Approximately 50% of the astrocytes and oligodendrocytes in the spared white matter of the epicenter die by 24 h after spinal cord injury (SCI), but their densities return to normal levels by 6 weeks.

Cell proliferation and replacement following contusive spinal cord injury.

After spinal cord injury (SCI), about 50% of the oligodendrocytes and astrocytes in the residual white matter at the injury site are lost by 24 h. However, chronically after SCI, the density of oligodendrocytes is normal. Previous studies have shown that the adult rat spinal cord contains a pool of proliferating glial progenitors whose progeny could help restore cell density after injury.

Chronic alterations in the cellular composition of spinal cord white matter following contusion injury.

Spinal cord injury (SCI) involves the loss of neurons and glia due to initial mechanical and secondary biochemical mechanisms. Treatment with the sodium channel blocker tetrodotoxin (TTX) reduces acute white matter pathology and increases both axon density and hindlimb function chronically at 6 weeks after injury. We investigated the cellular composition of residual white matter chronically to determine whether TTX also has a significant effect on the numbers and types of cells present.