Journal of neurotrauma
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Journal of neurotrauma · Jul 2022
ReviewTau pathology, metal dyshomeostasis and repetitive mild traumatic brain injury: an unexplored link paving the way for neurodegeneration.
Repetitive mild traumatic brain injury (r-mTBI), commonly experienced by athletes and military personnel, causes changes in multiple intracellular pathways, one of which involves the tau protein. Tau phosphorylation plays a role in several neurodegenerative conditions including chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disorder linked to repeated head trauma. There is now mounting evidence suggesting that tau phosphorylation may be regulated by metal ions (such as iron, zinc and copper), which themselves are implicated in aging and neurodegenerative disorders such as Alzheimer's disease (AD). ⋯ The authors highlight that metal dyshomeostasis has yet to be investigated in the context of repeat head trauma or CTE. Given the evidence that metal dyshomeostasis contributes to the onset and/or progression of neurodegeneration, and that CTE itself is a neurodegenerative condition, this brings to light an uncharted link that should be explored. The development of adequate models of r-mTBI and/or CTE will be crucial in deepening our understanding of the pathological mechanisms that drive the clinical manifestations in these conditions and also in the development of effective therapeutics targeted toward slowing progressive neurodegenerative disorders.
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Journal of neurotrauma · Jul 2022
Randomized Controlled TrialPlasma Neurofilament Light and Glial Fibrillary Acidic Protein Levels over Thirty Days in a Porcine Model of Traumatic Brain Injury.
To establish the clinical relevance of porcine model of traumatic brain injury (TBI) using the plasma biomarkers of injury with diffusion tensor imaging (DTI) over 30 days, we performed a randomized, blinded, pre-clinical trial using Yorkshire pigs weighing 7-10 kg. Twelve pigs were subjected to Sham injury (n = 5) by skin incision or TBI (n = 7) by controlled cortical impact. Blood samples were collected before the injury, then at approximately 5-day intervals until 30 days. ⋯ Porcine model of TBI replicates the acute increase in plasma biomarkers seen in clinical TBI. Further, long term white matter injury is confirmed in the areas such as the splenium and corona radiata. However, future study stratifying severe and mild TBI, as well as comparison with other subtypes of TBI such as diffuse axonal injury, may be warranted.
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Journal of neurotrauma · Jul 2022
Multicenter StudyFunctional short-term outcomes and mortality in children with severe traumatic brain injury - comparing decompressive craniectomy and medical management.
The effect of decompressive craniectomy (DC) on functional outcomes and mortality in children after severe head trauma is strongly debated. The lack of high-quality evidence poses a serious challenge to neurosurgeons' and pediatric intensive care physicians' decision making in critically ill children after head trauma. This study was conducted to compare DC and medical management in severely head-injured children with respect to short-term outcomes and mortality. ⋯ After risk adjustment by logistic regression modeling, the odds ratio was 1.56 (95% confidence interval 1.01-2.40) for poor outcome at intensive care unit discharge and 1.20 (0.74-1.95) for mortality after DC. In summary, DC was associated with increased odds for poor short-term outcomes in children with severe head trauma. This finding should temper enthusiasm for DC in children until a large randomized controlled trial has answered more precisely if DC in children is beneficial or increases rates of vegetative state.
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Journal of neurotrauma · Jul 2022
Correlation of blast-induced tympanic membrane perforation with peripheral cochlear synaptopathy.
The auditory organs, including the tympanic membrane, cochlea, and central auditory pathway, are the most fragile components of the human body when exposed to blast overpressure. Tympanic membrane perforation (TMP) is the most frequent symptom in blast-exposed patients. The impact of TMP on the inner ear and central auditory system, however, is not fully understood. ⋯ A decrease in the number of excitatory central synapses labeled by VGLUT-1 in the cochlear nucleus was observed, however, regardless of the absence or presence of TMP. Our findings suggest that blast-induced TMP mitigates peripheral cochlear synaptic disruption but leaves the central auditory synapses unaffected, indicating that central synaptic disruption is independent of TMP and peripheral cochlear synaptic disruption. Synaptic deterioration in the peripheral and central auditory systems can contribute to the promotion of blast-induced hearing impairment, including abnormal auditory perception.
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Traumatic brain injury (TBI) results in disparate outcomes ranging from persistent disorders of consciousness to symptom resolution. Despite the breadth and complexity of TBI recovery, most clinical trials dichotomize outcome by establishing an arbitrary cut-point, above and below which recovery is described as "favorable" and "unfavorable," respectively. For example, the widely used eight-level Glasgow Outcome Scale-Extended (GOSE) is typically collapsed into these two categories. ⋯ We illustrate the lack of standardization in defining "unfavorable" and "favorable" TBI outcome on the GOSE by identifying the broad range of cut-points, from a score of 3 (part-time supervision in the home required) to 7 (presence of some residual of symptoms), that have been used to dichotomize the GOSE. We also highlight the ethical concerns related to characterizing TBI outcomes solely from the perspective of investigators and clinicians, rather than patients and caregivers. Finally, we suggest that a pragmatic, immediate solution to GOSE dichotomization is to report the likelihood of achieving each of the eight GOSE outcome levels and propose a study design for a new patient- and caregiver-centered TBI outcome metric.