Articles: traumatic-brain-injuries.
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Journal of neurotrauma · Oct 2023
Sex differences in axonal dynamic responses under realistic tension using finite element models.
Existing axonal finite element models do not consider sex morphological differences or the fidelity in dynamic input. To facilitate a systematic investigation into the micromechanics of diffuse axonal injury, we develop a parameterized modeling approach for automatic and efficient generation of sex-specific axonal models according to specified geometrical parameters. Baseline female and male axonal models in the corpus callosum with random microtubule (MT) gap configurations are generated for model calibration and evaluation. ⋯ We find that peak strains in MTs and the Ranvier node and associated neurofilament failures in female axons are substantially higher than those in male axons because there are fewer MTs in the former and also because of the random nature of MT gap locations. Despite limitations in various model assumptions as a result of limited experimental data currently available, these findings highlight the need to systematically characterize MT gap configurations and to ensure a realistic model input for axonal dynamic simulations. Finally, this study may offer fresh and improved insight into the biomechanical basis of sex differences in brain injury, and sets the stage for more systematic investigations at the microscale in the future, both numerically and experimentally.
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Traumatic brain injury (TBI) is an important and growing cause of disability worldwide, and its cognitive consequences may be particularly significant. This study assessed the neuroprotective impacts of estradiol (E2), myrtenol (Myr), and the combination of the two on the neurological outcome, hemodynamic parameters, learning and memory, brain-derived neurotrophic factor (BDNF) level, phosphoinositide 3-kinases (PI3K/AKT) signaling, and inflammatory and oxidative factors in the hippocampus after TBI. ⋯ Our results propose that Myr and E2 have neuroprotective effects on cognition impairments due to TBI.
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Journal of neurotrauma · Oct 2023
Observational StudyCushing Index based on Cushing signs to predict in-hospital mortality and early intervention for minor head injury.
A considerable number of patients with mild traumatic brain injury have been known to "talk and die." Serial neurological examinations, however, have been the only method of determining the necessity of repeat computed tomography (CT), and no validated method has been available to predict early deterioration of minor head injury. This study aimed to evaluate the association between hypertension and bradycardia, a classic sign of raised intracranial pressure (Cushing reflex) on hospital arrival and determine the clinical consequences of minor head injury after blunt trauma. We created a new Cushing Index (CI) by dividing the systolic blood pressure by the heart rate (equaling the inverse number of the Shock Index, a score for hemodynamic stability) and hypothesized that a high CI would predict surgical intervention for deterioration and in-hospital death among patients with minor head injury. ⋯ Patients with high index also had a higher incidence of emergency cranial surgery within 24h after arrival than those with an intermediate CI (746 [6.4%] vs. 879 [5.4%]; OR = 1.20 [1.08-1.33]; p < 0.001). In addition, patients with low CI (equal to high Shock Index, meaning hemodynamically unstable) showed higher in-hospital death compared with those with intermediate CI (360 [3.3%] vs. 373 [2.3%]; p < 0.001). In conclusion, a high CI (high systolic blood pressure and low heart rate) on hospital arrival would be helpful in identifying patients with minor head injury who might experience deterioration and need close observation.
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Journal of neurotrauma · Oct 2023
Head Kinematics, Blood Biomarkers and Histology in Large Animal Models of Traumatic Brain Injury and Hemorrhagic Shock.
Traumatic brain injury (TBI) and severe blood loss resulting in hemorrhagic shock (HS) are each leading causes of mortality and morbidity worldwide, and present additional treatment considerations when they are comorbid (TBI+HS) as a result of competing pathophysiological responses. The current study rigorously quantified injury biomechanics with high precision sensors and examined whether blood-based surrogate markers were altered in general trauma as well as post-neurotrauma. Eighty-nine sexually mature male and female Yucatan swine were subjected to a closed-head TBI+HS (40% of circulating blood volume; n = 68), HS only (n = 9), or sham trauma (n = 12). ⋯ GFAP and NfL were both strongly associated with changes in systemic markers during general trauma and exhibited consistent time-dependent changes in individual sham animals. Finally, circulating GFAP was associated with histopathological markers of diffuse axonal injury and blood-brain barrier breach, as well as variations in device kinematics following TBI+HS. Current findings therefore highlight the need to directly quantify injury biomechanics with head mounted sensors and suggest that GFAP, NfL, and UCH-L1 are sensitive to multiple forms of trauma rather than having a single pathological indication (e.g., GFAP = astrogliosis).
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Intranasal insulin reduces lesion size and enhances memory capacity in traumatic brain injury (TBI) models, but the molecular mechanisms behind this neuroprotective action not yet understood. Here we used Feeney's free-falling method to construct TBI mouse models and administrated intranasal insulin, rapamycin, insulin and rapamycin, or normal saline to assess their effects on neurological functions, cerebral edema, and the expression of Iba1 in microglia through immunofluorescence assay. We also measured concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the brain using enzyme immunosorbent assay, investigated apoptosis with TUNEL staining and Western blotting, and evaluated autophagy, endoplasmic reticulum (ER) stress, and PI3K/Akt/mTOR signaling pathway with Western blotting. ⋯ TUNEL assay and Western blotting also indicated that intranasal insulin inhibited ER stress-mediated apoptosis. Interestingly, the mTOR inhibitor rapamycin partially blocked the pro-autophagy and anti-apoptosis effects of intranasal insulin both on days 1 and 3 post TBI. Our results suggest that intranasal insulin can ameliorate TBI by regulating autophagy and ER stress-mediated apoptosis through the PI3K/AKT/mTOR signaling pathway, providing a promising therapeutic strategy for TBI.