Journal of neurotrauma
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Journal of neurotrauma · Jan 2019
Comparative StudyPsychometric Comparisons of the Quality of Life after Brain Injury between Individuals with Mild and Those with Moderate/Severe Traumatic Brain Injuries.
This study compared psychometric properties of the Taiwanese version of the Quality of Life after Brain Injury (QOLIBRI) between patients with mild and those with moderate/severe traumatic brain injury (TBI). Of 683 participants, 548 had sustained a mild injury with Glasgow Coma Scale (GCS) scores of 13-15, and 135 had a moderate/severe injury with GCS scores of 3-12. The QOLIBRI comprises six domains: Cognition, Self, Daily Life and Autonomy, Social Relationships, Emotions, and Physical Problems. ⋯ While the psychometric performance of the QOLIBRI at the domain level was similar between the mild and moderate/severe TBI groups, certain items exhibited different functioning between the two groups. The reason why the two domains of the Emotions and Physical Problems performed poorly in the two TBI severity groups could be due to cross-cultural effects. The meanings of these DIF items, particularly for patients with a mild TBI, and factors contributing to the ceiling effect of the Emotions and Physical Problems domains in other ethnic Chinese populations need to be investigated further.
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Journal of neurotrauma · Jan 2019
Combining Brain Microdialysis and Translational Pharmacokinetic Modeling to Predict Drug Concentrations in Pediatric Severe Traumatic Brain Injury: The Next Step Toward Evidence-Based Pharmacotherapy?
Evidence-based analgosedation in severe pediatric traumatic brain injury (pTBI) management is lacking, and improved pharmacological understanding is needed. This starts with increased knowledge of factors controlling the pharmacokinetics (PK) of unbound drug at the target site (brain) and related drug effect(s). This prospective, descriptive study tested a pediatric physiology-based pharmacokinetic software model by comparing actual plasma and brain extracellular fluid (brainECF) morphine concentrations with predicted concentration-time profiles in severe pTBI patients (Glasgow Coma Scale [GCS], ≤8). ⋯ In addition, predicted brainECF concentration-time profiles fell within a 90% prediction interval of microdialysis brainECF drug concentrations when sampled from an uninjured area. Prediction was less accurate in injured areas. This approach of translational physiology-based PK modeling allows prediction of morphine concentration-time profiles in uninjured brain of individual patients and opens promising avenues towards evidence-based pharmacotherapies in pTBI.
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Journal of neurotrauma · Jan 2019
Mesenchymal Stem Cell-Derived Exosomes Provide Neuroprotection and Improve Long-Term Neurologic Outcomes in a Swine Model of Traumatic Brain Injury and Hemorrhagic Shock.
Combined traumatic brain injury (TBI) and hemorrhagic shock (HS) remains a leading cause of preventable death worldwide. Mesenchymal stem cell-derived exosomes have demonstrated promise in small animal models of neurologic injury. To investigate the effects of exosome treatment in a clinically realistic large animal model, Yorkshire swine underwent TBI and HS. ⋯ Animals treated with exosomes initiated neurocognitive testing earlier (days to initiation: NS = 9.6 ± 0.5 vs. NS + exosomes = 4.2 ± 0.8; p = 0.008); however, no difference was seen in time to mastery of tasks. In conclusion, treatment with exosomes attenuates the severity of neurologic injury and allows for faster neurologic recovery in a clinically realistic large animal model of TBI and HS.
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Journal of neurotrauma · Jan 2019
Controlled Cortical Impact Severity Results in Graded Cellular, Tissue, and Functional Responses in a Piglet Traumatic Brain Injury Model.
A number of pre-clinical rodent models have been developed in an effort to recapitulate injury mechanisms and identify potential therapeutics for traumatic brain injury (TBI), which is a major cause of death and long-term disability in the United States. The lack of restorative treatments for TBI, however, has led to considerable criticism of current pre-clinical therapeutic development strategies-namely, the translatability of widely used rodent models to human patients. The use of large animal models, such as the pig, with more brain anatomy and physiology comparable to humans may enhance the translational capacity of current pre-clinical animal models. ⋯ Similarly, the extent of neuronal loss, astrogliosis/astrocytosis, and white matter damage became more prominent as CCI parameters were increased. These cellular and tissue-level changes correlated with motor function deficits including swing/stance time, stride velocity, and two- versus three-limb support. The piglet TBI model described here could serve as a translational platform for studying TBI sequelae across injury severities and identifying novel therapeutics.
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Journal of neurotrauma · Jan 2019
Kir6.2, the Pore-Forming Subunit of ATP-Sensitive K+ Channels, Is Overexpressed in Human Posttraumatic Brain Contusions.
Brain contusions (BCs) are one of the most frequent lesions in patients with moderate and severe traumatic brain injury (TBI). BCs increase their volume due to peri-lesional edema formation and/or hemorrhagic transformation. This may have deleterious consequences and its mechanisms are still poorly understood. ⋯ The expression of Kir6.2 in neurons and microglia was also analyzed, but the observed differences were not statistically significant. However, a significant increase of Kir6.2 was found in glial fibrillary acidic protein (GFAP)-positive cells in contusion specimens. Our data suggest that further research on SUR1-regulated ionic channels may lead to a better understanding of key mechanisms involved in the pathogenesis of BCs, and may identify novel targeted therapeutic strategies.