Journal of neurotrauma
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Journal of neurotrauma · Apr 2023
Longitudinal Patterns of Functional Connectivity in Moderate-to-Severe Traumatic Brain Injury.
Longitudinal neuroimaging studies aid our understanding of recovery mechanisms in moderate-to-severe traumatic brain injury (TBI); however, there is a dearth of longitudinal functional connectivity research. Our aim was to characterize longitudinal functional connectivity patterns in two clinically important brain networks, the frontoparietal network (FPN) and the default mode network (DMN), in moderate-to-severe TBI. This inception cohort study of prospectively collected longitudinal data used resting-state functional magnetic resonance imaging (fMRI) to characterize functional connectivity patterns in the FPN and DMN. ⋯ Findings of early improvement but a tapering and possible decline in connectivity thereafter suggest that compensatory effects are time-limited. These later reductions in connectivity mirror growing evidence of behavioral and structural decline in chronic moderate-to-severe TBI. Targeting such declines represents a novel avenue of research and offers potential for improving clinical outcomes.
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Journal of neurotrauma · Apr 2023
Therapeutic role of microRNAs of small extracellular vesicles from human mesenchymal stromal/stem cells in the treatment of experimental traumatic brain injury.
Mesenchymal stem/stromal cells (MSC)-derived small extracellular vesicles (sEVs) possess therapeutic potential for treatment of traumatic brain injury (TBI). The essential role of micro ribonucleic acids (miRNAs) underlying the beneficial effects of MSC-derived sEVs for treatment of TBI remains elusive. The present study was designed to investigate the role of microRNAs in sEVs from MSCs with Argonaute 2 knockdown (Ago2-KD) in neurological recovery, neuroinflammation, and neurovascular remodeling in TBI rats. ⋯ The therapeutic effects of Ago2-KD-sEV were comparable to that of vehicle treatment. Our findings demonstrate that attenuation of Ago2 protein in MSCs reduces miRNAs in MSC-derived sEVs and abolishes exosome treatment-induced beneficial effects in TBI recovery, suggesting that miRNAs in MSC-derived sEVs play an essential role in reducing neuronal cell loss, inhibiting neuroinflammation, and augmenting angiogenesis and neurogenesis, as well as improving functional recovery in TBI. The findings underscore the important role of miRNAs in MSC-derived sEVs in the treatment of TBI.
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Journal of neurotrauma · Apr 2023
Innate and peripheral immune alterations after TBI are regulated in a gut microbiota-dependent manner in mice.
Traumatic brain injury (TBI) patients are at high risk for disruption of the gut microbiome. Previously, we have demonstrated that broad-spectrum antibiotic exposure after TBI drastically alters the gut microbiota and modulates neuroinflammation, neurogenesis, and long-term fear memory. However, these data did not determine if the impact of antibiotic exposure on the brain's response to injury was mediated directly by antibiotics or indirectly via modulation of the gut microbiota. ⋯ At 7 days post-injury, GF-VNAM had increased microglial activation, reduced infiltration of T cells, and decreased neurogenesis. Similarly, SPF mice exposed to antibiotics prior to but not after injury demonstrated similar alterations in neuroinflammation and neurogenesis compared with control mice. These data support our hypothesis implicating the gut microbiota as an important modulator of the neuroinflammatory process and neurogenesis after TBI and provide an exciting new approach for neuroprotective therapeutics for TBI.
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Journal of neurotrauma · Apr 2023
Review Meta AnalysisSystematic review, meta-analysis, and population attributable risk of dementia associated with traumatic brain injury in Civilians and Veterans.
Traumatic brain injury (TBI) is an established risk factor for dementia. However, the magnitude of risk is highly variable across studies. Identification of sub-populations at highest risk, with careful consideration of potential sources of bias, is urgently needed to guide public health policy and research into mechanisms and treatments. ⋯ Risk may be highest among younger adults, men, and cohorts in Asia. Efforts to prevent TBI and also to prevent post-TBI dementia are of high importance. Additionally, improved methods for diagnosing and tracking TBI on a public health level, such as national registries, may improve the quality and generalizability of future epidemiological studies investigating the association between TBI and dementia.
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Journal of neurotrauma · Apr 2023
Longitudinal abnormalities in white matter extracellular free water volume fraction and neuropsychological functioning in patients with traumatic brain injury.
Traumatic brain injury is a global public health problem associated with chronic neurological complications and long-term disability. Biomarkers that map onto the underlying brain pathology driving these complications are urgently needed to identify individuals at risk for poor recovery and to inform design of clinical trials of neuroprotective therapies. Neuroinflammation and neurodegeneration are two endophenotypes potentially associated with increases in brain extracellular water content, but the nature of extracellular free water abnormalities after neurotrauma and its relationship to measures typically thought to reflect traumatic axonal injury are not well characterized. ⋯ The summary specific anomaly score (SAS) for VF was significantly higher in TBI patients at 2 weeks and 6 months post-injury relative to controls. SAS for VF exhibited moderate correlation with neuropsychological functioning, particularly on measures of executive function. These findings indicate abnormalities in whole brain white matter extracellular water fraction in patients with TBI and are an important step toward identifying and validating noninvasive biomarkers that map onto the pathology driving disability after TBI.