Journal of neurotrauma
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Journal of neurotrauma · Aug 2024
The White Matter Fiber Tract Deforms Most in the Perpendicular Direction During In Vivo Volunteer Impacts.
White matter (WM) tract-related strains are increasingly used to quantify brain mechanical responses, but their dynamics in live human brains during in vivo impact conditions remain largely unknown. Existing research primarily looked into the normal strain along the WM fiber tracts (i.e., tract-oriented normal strain), but it is rarely the case that the fiber tract only endures tract-oriented normal strain during impacts. In this study, we aim to extend the in vivo measurement of WM fiber deformation by quantifying the normal strain perpendicular to the fiber tract (i.e., tract-perpendicular normal strain) and the shear strain along and perpendicular to the fiber tract (i.e., tract-oriented shear strain and tract-perpendicular shear strain, respectively). ⋯ Our study presents a comprehensive in vivo strain quantification toward a multifaceted understanding of WM dynamics. We find that the WM fiber tract deforms most in the perpendicular direction, illuminating new fundamentals of brain mechanics. The reported strain images can be used to evaluate the fidelity of computational head models, especially those intended to predict fiber deformation under noninjurious conditions.
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Journal of neurotrauma · Aug 2024
Mortality among Veterans following Traumatic Brain Injury: A VA Traumatic Brain Injury Model Systems Study.
Few studies have examined long-term mortality following traumatic brain injury (TBI) in a military population. This is a secondary analysis of a prospective, longitudinal study that examines long-term mortality (up to 10 years) post-TBI, including analyses of life expectancy, causes of death, and risk factors for death in service members and veterans (SM/V) who survived the acute TBI and inpatient rehabilitation. Among 922 participants in the study, the mortality rate was 8.3% following discharge from inpatient rehabilitation. ⋯ Those who died were also more likely to be older at injury, unemployed, non-active duty status, not currently married, and had longer post-traumatic amnesia, longer rehabilitation stays, worse independence and disability scores at rehabilitation discharge, and a history of mental health issues before injury. These findings indicate that higher disability and less social supportive infrastructure are associated with higher mortality. Our investigation into the vulnerabilities underlying premature mortality and into the major causes of death may help target future prevention, surveillance, and monitoring interventions.
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Journal of neurotrauma · Aug 2024
Evidence for Altered White Matter Organisation After Mild Traumatic Brain Injury: A Scoping Review on the Use of Diffusion MRI and Blood-Based Biomarkers to Investigate Acute Pathology and Relationship to Persistent Post-Concussion Symptoms.
Mild traumatic brain injury (mTBI) is the most common form of traumatic brain injury. Post-concussive symptoms typically resolve after a few weeks although up to 20% of people experience these symptoms for >3 months, termed persistent post-concussive symptoms (PPCS). Subtle white matter (WM) microstructural damage is thought to underlie neurological and cognitive deficits experienced post-mTBI. ⋯ Significant biomarker alterations were frequently associated with heightened symptom burden and prolonged recovery time post-injury. These data suggest that dMRI and blood-based biomarkers may be useful proxies of WM organization, although few studies assessed these complementary measures in parallel, and the relationship between modalities remains unclear. Further studies are warranted to assess the benefit of a combined biomarker approach in evaluating alterations to WM organization after mTBI.
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Journal of neurotrauma · Aug 2024
Molecular pathway changes associated with different post-conditioning exercise interventions after experimental TBI.
Traumatic brain injury (TBI) causes complex, time-dependent molecular and cellular responses, which include adaptive changes that promote repair and recovery, as well as maladaptive processes such as chronic inflammation that contribute to chronic neurodegeneration and neurological dysfunction. Hormesis is a well-established biological phenomenon in which exposure to low-dose toxins or stressors results in protective responses to subsequent higher-level stressors or insults. Hormetic stimuli show a characteristic U-shaped or inverted J-shaped dose-response curve, as well as being time and exposure-frequency dependent, similar to pre-conditioning and post-conditioning actions. ⋯ Exercise initiated at a more delayed timepoint of 6 weeks after injury and continuing for 4 weeks was more effective than that during the acute phase. The delayed paradigm was also more effective than exercise initiated at 10 weeks after injury and continuing for 8 weeks, consistent with hormetic responses in other models and species. Overall, our study delineates regional and interventional parameters, as well as related molecular pathway changes, associated with post-conditioning exercise treatment, which may help inform future translational interventional strategies.
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Journal of neurotrauma · Aug 2024
Hepatocyte growth factor delivery to injured cervical spinal cord using an engineered biomaterial protects respiratory neural circuitry and preserves functional diaphragm innervation.
A major portion of spinal cord injury (SCI) cases occur in the cervical region, where essential components of the respiratory neural circuitry are located. Phrenic motor neurons (PhMNs) housed at cervical spinal cord level C3-C5 directly innervate the diaphragm, and SCI-induced damage to these cells severely impairs respiratory function. In this study, we tested a biomaterial-based approach aimed at preserving this critical phrenic motor circuitry after cervical SCI by locally delivering hepatocyte growth factor (HGF). ⋯ HGF hydrogel also preserved PhMN innervation of the diaphragm, as assessed by both retrograde PhMN tracing and detailed neuromuscular junction morphological analysis. Furthermore, HGF hydrogel significantly decreased lesion size and degeneration of cervical motor neuron cell bodies, as well as reduced levels surrounding the injury site of scar-associated chondroitin sulfate proteoglycan molecules that limit axon growth capacity. Our findings demonstrate that local biomaterial-based delivery of HGF hydrogel to injured cervical spinal cord is an effective strategy for preserving respiratory circuitry and diaphragm function.