Journal of neurotrauma
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Journal of neurotrauma · Aug 2023
Adolescents with More Oculomotor and Vestibular Signs of Sport-Related Concussion Benefit from Aerobic Exercise: an Exploratory Analysis.
Abstract Early targeted heart rate (HR) aerobic exercise has been shown to reduce the duration of recovery from sport-related concussion (SRC) as well as the incidence of persistent post-concussive symptoms (PPCS). It is not known, however, if more severe oculomotor and vestibular presentations of SRC benefit from a prescription of aerobic exercise. The current study is an exploratory analysis of two published randomized controlled trials that compared aerobic exercise within 10 days of injury with a placebo-like stretching intervention. ⋯ Aerobic exercise (hazard ratio = 0.621 [0.412, 0.936], p = 0.023) reduced recovery times even when controlling for site (hazard ratio = 0.461 [0.303, 0.701], p < 0.001), severity (hazard ratio = 0.528 [0.325, 0.858], p = 0.010) and the interaction term of intervention and severity (hazard ratio = 0.972 [0.495, 1.909], p = 0.935). Adolescents who presented with >3 signs and were assigned to the placebo-like stretching group had a PPCS incidence of 38%, which was the highest of all subgroups (aerobic exercise and ≤3 findings: 8%; stretching and ≤3 findings: 11%; aerobic exercise and >3 findings: 21%). This exploratory study provides pilot evidence that prescribed sub-symptom threshold aerobic exercise treatment early after SRC may be effective for adolescents with more oculomotor and vestibular physical examination signs and should be validated in future adequately powered trials.
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Journal of neurotrauma · Aug 2023
Traumatic axonal injury in the optic nerve: the selective role of SARM1 in the evolution of distal axonopathy.
Traumatic axonal injury (TAI), thought to be caused by rotational acceleration of the head, is a prevalent neuropathology in traumatic brain injury (TBI). TAI in the optic nerve is a common finding in multiple blunt-force TBI models and hence a great model to study mechanisms and treatments for TAI, especially in view of the compartmentalized anatomy of the visual system. We have previously shown that the somata and the proximal, but not distal, axons of retinal ganglion cells (RGC) respond to DLK/LZK blockade after impact acceleration of the head (IA-TBI). ⋯ Quantitative analyses on proximal and distal axons and RGC somata revealed that different neuronal domains exhibit differential vulnerability, with distal axon segments showing more severe degeneration compared with proximal segments and RGC somata. Importantly, we found that Sarm1 KO had a profound effect in the distal optic nerve by suppressing axonal degeneration by up to 50% in the first 2 weeks after IA-TBI, with a continued but lower effect at 3 weeks, while also suppressing microglial activation. Sarm1 KO had no evident effect on the initial traumatic disconnection and did not ameliorate the proximal optic axonopathy or the subsequent attrition of RGCs, indicating that the fate of different axonal segments in the course of TAI may depend on distinct molecular programs within axons.
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Journal of neurotrauma · Aug 2023
Investigating the Effect of Brain Size on Deformation Magnitude using Subject-Specific Finite Element Models.
Abstract In the last decade, computational models of the brain have become the gold standard tool for investigating traumatic brain injury (TBI) mechanisms and developing novel protective equipment and other safety countermeasures. However, most studies utilizing finite element (FE) models of the brain have been conducted using models developed to represent the average neuroanatomy of a target demographic, such as the 50th percentile male. Although this is an efficient strategy, it neglects normal anatomical variations present within the population and their contributions on the brain's deformation response. ⋯ Both techniques indicated a strong linear relationship between ICV and MPS-95, with MPS-95 varying by approximately 5% between the smallest and largest brains. This difference represented up to 40% of the mean strain across all subjects. This study represents a comprehensive assessment of the relationships between brain anatomy and deformation, which is crucial for the development of personalized protective equipment, identifying individuals at higher risk of injury, and using computational models to aid clinical diagnostics of TBI.
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Journal of neurotrauma · Aug 2023
Optimizing choice and timing of behavioral outcome tests following repetitive mild traumatic brain injury: A machine learning-based approach on multiple preclinical experiments.
Repetitive mild traumatic brain injury (rmTBI) is a potentially debilitating condition with long-term sequelae. Animal models are used to study rmTBI in a controlled environment, but there is currently no established standard battery of behavioral tests used. Primarily, we aimed to identify the best combination and timing of behavioral tests to distinguish injured from uninjured animals in rmTBI studies, and secondarily, to determine whether combinations of independent experiments have better behavioral outcome prediction accuracy than individual experiments. ⋯ Combinations of open field tests and elevated plus mazes also performed well (AUC = 0.92), as did the forced swim test alone (AUC = 0.90). In summary, multiple heterogeneous experiments tended to predict outcome better than individual experiments, and MWM 3-4 months after injury was the optimal test, also several combinations also performed well. In order to design future pre-clinical rmTBI trials, we have included an interactive application available online utilizing the data from the study via the Supplementary URL.