Journal of neurotrauma
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Journal of neurotrauma · Jun 2021
Hippocampal-Dependent Cognitive Dysfunction Following Repeated Diffuse Rotational Brain Injury in Male and Female Mice.
Cognitive dysfunction is a common, often long-term complaint following acquired traumatic brain injury (TBI). Cognitive deficits suggest dysfunction in hippocampal circuits. The goal of the studies described here is to phenotype in both male and female mice the hippocampal-dependent learning and memory deficits resulting from TBI sustained by the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) device-a model that delivers both a contact-concussion injury as well as unrestrained rotational head movement. ⋯ Pathologically, the injury was characterized by white matter damage as observed by silver staining and glial fibrillary acidic protein (astrogliosis) in the optic tracts, with milder damage seen in the corpus callosum, and fimbria and brainstem (cerebral peduncles) of some animals. No changes in the density of GABAergic parvalbumin-expressing cells in the hippocampus, amygdala, or parietal cortex were found. This experiment confirmed significant sexually dimorphic cognitive impairments following a repeated, diffuse brain injury.
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Journal of neurotrauma · Jun 2021
Evaluation of Diffusion Tensor Imaging and Fluid Based Biomarkers in a Large Animal Trial of Cyclosporine in Focal Traumatic Brain Injury.
All phase III trials evaluating medical treatments for traumatic brain injury (TBI), performed to date, have failed. To facilitate future success there is a need for novel outcome metrics that can bridge pre-clinical studies to clinical proof of concept trials. Our objective was to assess diffusion tensor imaging (DTI) and biofluid-based biomarkers as efficacy outcome metrics in a large animal study evaluating the efficacy of cyclosporine in TBI. ⋯ Normalized fractional anisotropy (FA) was significantly (p = 0.027) higher in in the treatment group, indicating preserved tissue integrity with treatment. For the biomarkers, we observed a statistical trend of a decreased level of NF-L in CSF (p = 0.051), in the treatment group relative to placebo, indicating less axonal injury. Our findings suggest that DTI, and possibly CSF NF-L, may be feasible as translational end-points assessing neuroprotective drugs in TBI.
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Journal of neurotrauma · Jun 2021
Randomized Controlled TrialRestart TICrH Trial Design: an adaptive randomized trial of time intervals to restart direct oral anticoagulants after traumatic intracranial hemorrhage.
Anticoagulants prevent thrombosis and death in patients with atrial fibrillation and venous thromboembolism (VTE) but also increase bleeding risk. The benefit/risk ratio favors anticoagulation in most of these patients. However, some will have a bleeding complication, such as the common trip-and-fall brain injury in elderly patients that results in traumatic intracranial hemorrhage. ⋯ Clinicians generally agree that anticoagulation should be restarted but disagree about when. This uncertainty leads to long restart delays causing a large, potentially preventable burden of strokes and VTE, which has been unaddressed because of the absence of high quality evidence. Restart Traumatic Intracranial Hemorrhage (the "r" distinguished intracranial from intracerebral) (TICrH) is a prospective randomized open label blinded end-point response-adaptive clinical trial that will evaluate the impact of delays to restarting direct oral anticoagulation (1, 2, or 4 weeks) on the composite of thrombotic events and bleeding in patients presenting after traumatic intracranial hemorrhage.
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Journal of neurotrauma · Jun 2021
ReviewMolecular and DTI Biomarkers of Traumatic Brain Injury: Principles for Investigation and Integration.
The last 20 years have seen the advent of new technologies that enhance the diagnosis and prognosis of traumatic brain injury (TBI). There is recognition that TBI affects the brain beyond initial injury, in some cases inciting a progressive neuropathology that leads to chronic impairments. Medical researchers are now searching for biomarkers to detect and monitor this condition. ⋯ Integration of these technologies could advance models of disease prognosis, ultimately improving care. To date, however, few studies have explored relationships between molecular and DTI variables in patients with TBI. Here, we provide a short primer on each technology, review the latest research, and discuss how these biomarkers may be incorporated in future studies.
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Journal of neurotrauma · Jun 2021
Patterns of Functional Change 5 to 10 years Following Moderate-Severe Traumatic Brain Injury.
This study aims to characterize the patterns of functional change experienced between 5 and 10 years after moderate-severe traumatic brain injury (TBI). The study included TBI Model Systems national database participants (N = 372) at six sites who experienced TBI, received inpatient rehabilitation, and were followed at 5 and 10 years post-TBI. Outcome measures included self- or proxy-reported Functional Independence Measure (FIMTM) structured interview at 5 and 10 years post-TBI and domain change indices (DCIs) at 10 years to assess subjective change over the previous 5 years. ⋯ Age at injury, post-traumatic amnesia duration, FIM, and depression and anxiety at year 5 were associated with FIM change and DCI measures. Although most persons with moderate-severe TBI do not experience widespread change from year 5 to 10 on individual FIM subscales or perceived domain-specific subscales, the vast majority do report change in one or more domains, with more improvement than decline and more change in subjective DCI than in FIM. Clinicians and researchers should be alert to the possibility of both positive and deleterious changes many years after TBI.