Aircraft cabins are routinely pressurized to the equivalent of 8000 ft altitude. Exposure of lab animals to aeromedical evacuation relevant hypobaria after traumatic brain injury worsens neurological outcomes, which is paradoxically exacerbated by hyperoxia. This study tested the hypothesis that exposure of rats to hypobaria following cortical impact reduces cerebral blood flow, increases neuroinflammation, and alters brain neurochemistry.
View Article and Find Full Text PDFDomestic ferrets (Mustela putorius furo) are an emerging model species in biomedical research. While behavioral studies are a critical translational tool for evaluating neurologic function in disease models and toxicology studies, there is a lack of ferret-specific behavioral assays and corresponding data on baseline behavior. Play behavior is a promising target for evaluation of psychological well-being, particularly because ferrets engage in solitary and social play well into adulthood.
View Article and Find Full Text PDFTraumatic brain injury (TBI) has been associated with the development of indirect acute respiratory distress syndrome (ARDS). However, the causative relationship between TBI and lung injury remains unclear. To explore potential mechanisms linking TBI with the development of ARDS, we characterized the effects of serum factors released following TBI and hemorrhagic shock (HS) in a rat model on the pulmonary endothelial cell (EC) barrier dysfunction, a key feature of ARDS.
View Article and Find Full Text PDFAeromedical evacuation-relevant hypobaria after traumatic brain injury (TBI) leads to increased neurological injury and death in rats relative to those maintained under normobaria. Applicability of rodent brain injury research to humans may be limited, however, by differences in neuroanatomy. Therefore, we developed a model in which ferrets are exposed to polytrauma consisting of controlled cortical impact TBI and hemorrhagic shock subjected 24 h later to 6 h of hypobaria or normobaria.
View Article and Find Full Text PDFHyperpolarized magnetic resonance spectroscopic imaging (MRSI) of [1-C]pyruvate metabolism has previously been used to assess the effects of traumatic brain injury (TBI) in rats. Here, we show that MRSI can be used in conjunction with dichloroacetate to measure the phosphorylation state of pyruvate dehydrogenase (PDH) following mild-to-moderate TBI, and that measurements can be repeated in a longitudinal study to monitor the course of injury progression and recovery. We found that the level of C-bicarbonate and the bicarbonate-to-lactate ratio decreased on the injured side of the brain four hours after injury and continued to decrease through day 7.
View Article and Find Full Text PDFRats exposed to hypobaria equivalent to what occurs during aeromedical evacuation within a few days after isolated traumatic brain injury exhibit greater neurologic injury than those remaining at sea level. Moreover, administration of excessive supplemental O2 during hypobaria further exacerbates brain injury. This study tested the hypothesis that exposure of rats to hypobaria following controlled cortical impact (CCI)-induced brain injury plus mild hemorrhagic shock worsens multiple organ inflammation and associated mortality.
View Article and Find Full Text PDFMitochondria are both a primary source of reactive oxygen species (ROS) and a sensitive target of oxidative stress; damage to mitochondria can result in bioenergetic dysfunction and both necrotic and apoptotic cell death. These relationships between mitochondria and cell death are particularly strong in both acute and chronic neurodegenerative disorders. ROS levels are affected by both the production of superoxide and its toxic metabolites and by antioxidant defense mechanisms.
View Article and Find Full Text PDFBackground: Animal studies indicate that maintaining physiologic O levels (normoxia) immediately after restoration of spontaneous circulation (ROSC) from cardiac arrest (CA) results in less hippocampal neuronal death compared to animals ventilated with 100% O. This study tested the hypothesis that beneficial effects of avoiding hyperoxia following CA are apparent in the cerebellum and therefore not limited to one brain region.
Methods: Adult beagles were anesthetized and mechanically ventilated.
Background: Injured warfighters air evacuated to tertiary medical care facilities are subjected to many stresses that may promote the development of sepsis. In this study, we tested the hypothesis that exposure to "in-flight" hypobaria and/or hyperoxia within 24 hours after onset of intra-abdominal infection in rats accelerates the development and/or severity of sepsis and neurologic injury in survivors.
Methods: Sprague-Dawley rats underwent cecal ligation/puncture (CLP) or sham procedures.
Background: Occupants of military vehicles targeted by explosive devices often suffer from traumatic brain injury (TBI) and are typically transported by the aeromedical evacuation (AE) system to a military medical center within a few days. This study tested the hypothesis that exposure of rats to AE-relevant hypobaria worsens cerebral axonal injury and neurologic impairment caused by underbody blasts.
Methods: Anesthetized adult male rats were secured within cylinders attached to a metal plate, simulating the hull of an armored vehicle.
Blast-related traumatic brain injury (bTBI) resulting from improvised explosive devices is the hallmark injury of recent wars, and affects many returning veterans who experienced either direct or indirect exposure. Many of these veterans have long-term neurocognitive symptoms. However, there is very little evidence to show whether blast-induced acceleration alone, in the absence of secondary impacts, can cause mild TBI.
View Article and Find Full Text PDFJ Trauma Acute Care Surg
May 2016
Background: Many traumatic brain injury (TBI) patients experience additional injuries, including those that result in hemorrhagic shock (HS). Interactions between HS and TBI can include reduced brain O2 delivery, resulting in partial cerebral ischemia and worse neurologic outcome. This study tested the hypothesis that inspiration of 100% O2 during resuscitation following TBI and HS improves survival, reduces brain lesion volume, and improves neurologic outcome compared with resuscitation in the absence of supplemental O2.
View Article and Find Full Text PDFJ Trauma Acute Care Surg
September 2014
Background: More than 300,000 US war fighters in Operations Iraqi and Enduring Freedom have sustained some form of traumatic brain injury (TBI), caused primarily by exposure to blasts. Many victims are occupants in vehicles that are targets of improvised explosive devices. These underbody blasts expose the occupants to vertical acceleration that can range from several to more than 1,000 G; however, it is unknown if blast-induced acceleration alone, in the absence of exposure to blast waves and in the absence of secondary impacts, can cause even mild TBI.
View Article and Find Full Text PDFDiffusion Kurtosis Imaging (DKI) provides quantifiable information on the non-Gaussian behavior of water diffusion in biological tissue. Changes in water diffusion tensor imaging (DTI) parameters and DKI parameters in several white and gray matter regions were investigated in a mild controlled cortical impact (CCI) injury rat model at both the acute (2 h) and the sub-acute (7 days) stages following injury. Mixed model ANOVA analysis revealed significant changes in temporal patterns of both DTI and DKI parameters in the cortex, hippocampus, external capsule and corpus callosum.
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