Quantifying acute changes in neurometabolism following blast-induced traumatic brain injury.

Brain health is largely dependent on the metabolic regulation of amino acids. Brain injuries, diseases, and disorders can be detected through alterations in free amino acid (FAA) concentrations; and thus, mapping the changes has high diagnostic potential. Common methods focus on optimizing neurotransmitter quantification; however, recent focus has expanded to investigate the roles of molecular precursors in brain metabolism. An isocratic method using high performance liquid chromatography with electrochemical cell detection was developed to quantify a wide range of molecular precursors and neurotransmitters: alanine, arginine, aspartate, serine, taurine, threonine, tyrosine, glycine, glutamate, glutamine, and γ-Aminobutyric acid (GABA) following traumatic brain injury. First, baseline concentrations were determined in the serum, cerebrospinal fluid, hippocampus, cortex, and cerebellum of naïve male Sprague Dawley rats. A subsequent study was performed investigating acute changes in FAA concentrations following blast-induced traumatic brain injury (bTBI). Molecular precursor associated FAAs decreased in concentration at 4 h after injury in both the cortex and hippocampus while those serving as neurotransmitters remained unchanged. In particular, the influence of oxidative stress on the observed changes within alanine and arginine pathways following bTBI should be further investigated to elucidate the full therapeutic potential of these molecular precursors at acute time points.

A closed-body preclinical model to investigate blast-induced spinal cord injury.

Blast-induced spinal cord injuries (bSCI) are common and account for 75% of all combat-related spinal trauma. It remains unclear how the rapid change in pressure contributes to pathological outcomes resulting from these complex injuries. Further research is necessary to aid in specialized treatments for those affected. The purpose of this study was to develop a preclinical injury model to investigate the behavior and pathophysiology of blast exposure to the spine, which will bring further insight into outcomes and treatment decisions for complex spinal cord injuries (SCI). An Advanced Blast Simulator was used to study how blast exposure affects the spinal cord in a non-invasive manner. A custom fixture was designed to support the animal in a position that protects the vital organs while exposing the thoracolumbar region of the spine to the blast wave. The Tarlov Scale and Open Field Test (OFT) were used to detect changes in locomotion or anxiety, respectively, 72 h following bSCI. Spinal cords were then harvested and histological staining was performed to investigate markers of traumatic axonal injury (ß-APP, NF-L) and neuroinflammation (GFAP, Iba1, S100ß). Analysis of the blast dynamics demonstrated that this closed-body model for bSCI was found to be highly repeatable, administering consistent pressure pulses following a Friedlander waveform. There were no significant changes in acute behavior; however, expression of ß-APP, Iba1, and GFAP significantly increased in the spinal cord following blast exposure (p < 0.05). Additional measures of cell count and area of positive signal provided evidence of increased inflammation and gliosis in the spinal cord at 72 h after blast injury. These findings indicated that pathophysiological responses from the blast alone are detectable, likely contributing to the combined effects. This novel injury model also demonstrated applications as a closed-body SCI model for neuroinflammation enhancing relevance of the preclinical model. Further investigation is necessary to assess the longitudinal pathological outcomes, combined effects from complex injuries, and minimally invasive treatment approaches.