Journal of neurotrauma
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Journal of neurotrauma · Jun 2021
Nitric oxide/cGMP signaling via guanylyl cyclase isoform 1 mediates early changes in synaptic transmission and brain edema formation after TBI.
Traumatic brain injury (TBI) often induces structural damage, disruption of the blood-brain barrier (BBB), neurodegeneration, and dysfunctions of surviving neuronal networks. Nitric oxide (NO) signaling has been suggested to affect brain functions after TBI. The NO exhibits most of its biological effects by activation of the primary targets-guanylyl cyclases (NO-GCs), which exists in two isoforms (NO-GC1 and NO-GC2), and the subsequently produced cyclic guanosine monophosphate (cGMP). ⋯ Interestingly, NO-GC1 KO mice revealed relatively less BBB rupture and a weaker brain edema formation early after TBI. Further, lack of NO-GC1 also prevented the impaired synaptic transmission and network function that were observed in TBI-treated WT mice. These data suggest that NO-GC1 signaling mediates early brain damage and the strength of ipsilateral cortical network in the early phase after TBI.
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Journal of neurotrauma · Jun 2021
Case ReportsTractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study.
Diffusion tractography magnetic resonance imaging (MRI) can infer changes in network connectivity in patients with traumatic brain injury (TBI), but the pathological substrates of disconnected tracts have not been well defined because of a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750-μm isotropic resolution, followed by histopathological evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. ⋯ Multiple linear regression revealed that tract disruption strongly correlated with the density of APP-positive axonal swellings and neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.
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Journal of neurotrauma · Jun 2021
Development of a blast exposure estimator from a DoD-wide survey study on military service members.
Long-term, repeated exposure to low-intensity blast overpressure is a potential causal factor of lasting outcomes reminiscent of post-concussion syndrome. Wearable blast sensor engineers are exploring elements of blast that are associated with outcomes. Currently, however, there are no devices that can truly record all blasts experienced by an individual. ⋯ If repetitive, low-intensity blast exposure has even a subtle effect over time, operational readiness could be negatively impacted. A threshold of exposure can inform decisions about how to reduce detrimental exposure. The GBEV can be used to track ongoing exposure and potentially identify those who may be at risk for developing blast-related outcomes.
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Journal of neurotrauma · Jun 2021
CONCUSSION ACUTELY DECREASES PLASMA GLYCEROPHOSPHOLIPIDS IN ADOLESCENT MALE ATHLETES.
Concussions are frequent in sports and can contribute to significant and long-lasting neurological disability. Adolescents are particularly susceptible to concussions, with accurate determination of the injury challenging. Our previous study demonstrated that concussion diagnoses could be aided by metabolomics profiling and machine learning, with particular weighting on changes in plasma glycerophospholipids (PCs). ⋯ Importantly, combining these four PCs produced an AUC of 0.96 for concussion diagnoses (p < 0.001; 95% confidence interval, 0.89, 1.00). Our data suggest that as few as four circulating PCs may provide excellent diagnostic potential for adolescent concussion. External validation is required in larger cohorts.
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Journal of neurotrauma · Jun 2021
Differential DNA methylation of the genes for amyloid precursor protein, tau and neurofilaments in human traumatic brain injury.
Traumatic brain injury (TBI) is an established risk factor for neurodegenerative disorders and dementias. Epigenetic modifications, such as DNA methylation, may alter the expression of genes without altering the DNA sequence in response to environmental factors. We hypothesized that DNA methylation changes may occur in the injured human brain and be implicated in the neurodegenerative aftermath of TBI. ⋯ Among the top 20 differentially methylated CpG sites, 11 were in the APP gene. In addition, the EWAS evaluating 828,888 CpG sites revealed 308 differentially methylated CpG sites in genes related to cellular/anatomical structure development, cell differentiation, and anatomical morphogenesis. These preliminary findings provide the first evidence of an altered DNA methylome in the injured human brain, and may have implications for the neurodegenerative disorders associated with TBI.