Journal of neurotrauma
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Journal of neurotrauma · Aug 2016
Autophagy modulation by lanthionine ketimine ethyl ester improves long-term outcome following central fluid percussion injury in the mouse.
Diffuse axonal injury is recognized as a progressive and long-term consequence of traumatic brain injury. Axonal injury can have sustained negative consequences on neuronal functions such as anterograde and retrograde transport and cellular processes such as autophagy that depend on cytoarchitecture and axon integrity. These changes can lead to somatic atrophy and an inability to repair and promote plasticity. ⋯ Lanthionine ketimine ethyl ester, a bioavailable derivative of a natural sulfur amino acid metabolite, has demonstrated effects on autophagy both in vitro and in vivo. Thirty minutes after a moderate central fluid percussion injury and throughout the survival period, lanthionine ketimine ethyl ester was administered, and mice were subsequently evaluated for learning and memory impairments and biochemical and histological changes over a 5-week period. Lanthionine ketimine ethyl ester, which we have shown previously to modulate autophagy markers and alleviate pathology and slow cognitive decline in the 3 × TgAD mouse model, spared cognition and pathology after central fluid percussion injury through a mechanism involving autophagy modulation.
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Journal of neurotrauma · Aug 2016
LIF Haplodeficiency Desynchronizes Glial Reactivity and Exacerbates Damage and Functional Deficits After a Concussive Brain Injury.
Reactions of both astrocytes and microglia to central nervous system injury can be beneficial or detrimental to recovery. To gain insights into the functional importance of gliosis, we developed a new model of adolescent closed-head injury (CHI) and interrogated the behavioral, physiological, and cellular outcomes after a concussive CHI in leukemia inhibitory factor (LIF) haplodeficient mice. ⋯ The prolonged accumulation of neurological impairment was accompanied by desynchronization of the gliotic response, increased cell death, axonal degeneration, diminished callosal compound action potential, and hypomyelination. Our results clearly show that LIF is an essential injury-induced cytokine that is required to prevent the propagation of secondary neurodegeneration.
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Journal of neurotrauma · Aug 2016
Intravenous Administration of Simvastatin improves Cognitive Outcome following Severe Traumatic Brain Injury in Rats.
Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor commonly used to reduce serum cholesterol. The beneficial effects of oral simvastatin have been reported in pre-clinical models of traumatic brain injury (TBI). The current study was designed to evaluate the potential beneficial effects of simvastatin in a model of severe penetrating TBI using an intravenous (IV) route of administration. ⋯ Biomarker and cytokine analysis showed that IV simvastatin significantly reduced GFAP, interleukin (IL)-1α, and IL-17 serum levels by 4.0-, 2.6-, and 7.0-fold, respectively, at 4 h post-injury. Collectively, our results demonstrate that IV simvastatin provides significant protection against injury-induced cognitive dysfunction and reduces TBI-specific biomarker levels. Further research is warranted to identify the optimal dose and therapeutic window for IV delivery of simvastatin in models of severe TBI.
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Journal of neurotrauma · Aug 2016
ReviewA State of the Science Overview of Randomised Controlled Trials evaluating Acute Management of Moderate to Severe Traumatic Brain Injury.
Moderate-to-severe traumatic brain injury (TBI) remains a major global challenge, with rising incidence, unchanging mortality and lifelong impairments. State-of-the-science reviews are important for research planning and clinical decision support. This review aimed to identify randomized controlled trials (RCTs) evaluating interventions for acute management of moderate/severe TBI, synthesize key RCT characteristics and findings, and determine their implications on clinical practice and future research. ⋯ Considerable investment of resources in producing 191 completed RCTs for acute TBI management has resulted in very little translatable evidence. This may result from broad distribution of research effort, small samples, preponderance of single-center RCTs, and methodological shortcomings. More sophisticated RCT design, large multi-center RCTs in priority areas, increased focus on pre-clinical research, and alternatives to RCTs, such as comparative effectiveness research and precision medicine, are needed to fully realize the potential of acute TBI research to benefit patients.
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Journal of neurotrauma · Aug 2016
The Economic Burden of Autonomic Dysreflexia during Hospitalization for Individuals with Spinal Cord Injury.
We sought to determine the economic burden of autonomic dysreflexia (AD) from the perspective of the Canadian healthcare system in a case series of individuals with spinal cord injury (SCI) presenting to emergency care. In doing so, we sought to illustrate the potential return on investments in the translation of evidence-informed practices and developments in the prevention, diagnosis, and management of AD. Activity-based costing methodology was employed to estimate the direct healthcare or hospitalization costs of AD following presentation to the emergency department. ⋯ Emergency room admissions resulting from AD can result in dramatic healthcare costs. Delayed diagnosis and inefficient management of AD may lead to further complications, adding to the strain on already limited healthcare resources. Prompt recognition of AD; broader translation of evidence-informed practices; and novel diagnosis, self-management, and/or therapeutic/pharmaceutical applications may prove to mitigate the burden of AD and improve patient well-being.