Journal of neurotrauma
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Journal of neurotrauma · Apr 2022
Head impact exposure, grey matter volume, and moderating effects of estimated IQ and educational attainment in former athletes at midlife.
Repetitive head impact (RHI) exposure has been associated with differences in brain structure among younger active athletes, most often within the hippocampus. Studies of former athletes at early-midlife are limited. We investigated the association between RHI exposure and gray matter (GM) structure, as well as moderating factors, among former athletes in early-midlife. ⋯ Consistent with studies involving younger, active athletes, smaller hippocampal volumes were selectively associated with greater RHI exposure among former collegiate football players at midlife. This relationship was moderated by higher levels of education. Future longitudinal studies are needed to investigate the course of possible changes that can occur between early-midlife and older ages, as well as the continued protective effect of education and other potential influential factors.
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Journal of neurotrauma · Apr 2022
RNA Binding Motif 5 Gene Deletion Modulates Cell Signaling in a Sex-Dependent Manner but not Hippocampal Cell Death.
RNA-binding motif 5 (RBM5) is a pro-death tumor suppressor gene in cancer cells. It remains to be determined if it is neurotoxic in the brain or rather if it plays a fundamentally different role in the central nervous system (CNS). Brain-specific RBM5 knockout (KO) mice were given a controlled cortical impact (CCI) traumatic brain injury (TBI). ⋯ Finally, gene analysis revealed increased estrogen receptor α (ERα) levels in the KO hippocampus in females and may suggest a novel mechanism to explain sex-dimorphic effects on cell signaling. In summary, RBM5 inhibition did not affect hippocampal survival after a TBI in vivo but did modify targets involved in neural signal transduction/Ca2+ signaling pathways. Findings here support the view that RBM5 may serve a purpose in the CNS that is dissimilar from its traditional pro-death role in cancer.
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Journal of neurotrauma · Apr 2022
Combined Inhibition of Fyn and c-Src Protects Hippocampal Neurons and Improves Spatial Memory via ROCK after Traumatic Brain Injury.
Our previous studies demonstrated that traumatic brain injury (TBI) and ventricular administration of thrombin caused hippocampal neuron loss and cognitive dysfunction via activation of Src family kinases (SFKs). Based on SFK localization in brain, we hypothesized SFK subtypes Fyn and c-Src, as well as SFK downstream molecule Rho-associated protein kinase (ROCK), contribute to cell death and cognitive dysfunction after TBI. We administered nanoparticle wrapped small interfering RNA (siRNA)-Fyn and siRNA-c-Src, or ROCK inhibitor Y-27632 to adult rats subjected to moderate lateral fluid percussion (LFP)-induced TBI. ⋯ The combination of siRNA-Fyn and siRNA-c-Src, but neither alone, prevented hippocampal neuron loss and spatial memory deficits after TBI. The ROCK inhibitor Y-27632 also prevented hippocampal neuronal loss and spatial memory deficits after TBI. The data suggest that the combined actions of three kinases (Fyn, c-Src, ROCK) mediate hippocampal neuronal cell death and spatial memory deficits produced by LFP-TBI, and that inhibiting this pathway prevents the TBI-induced cell death and memory deficits.
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Journal of neurotrauma · Apr 2022
Review Meta AnalysisMild Traumatic Brain Injury in Elderly Patients Receiving Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis.
The aim of this work was to conduct a systematic review and meta-analysis of studies reporting on the risk of traumatic intracerebral hemorrhage (tICH), the course of tICH, and its treatment and mortality rates in elderly mild traumatic brain injury (mTBI) patients using direct oral anticoagulants (DOACs). We consulted PubMed and Embase for relevant cohort and case-control studies with a control group. Two authors independently selected studies, assessed methodological quality, and extracted outcome data. ⋯ There was no significant difference in neurosurgical intervention rate between patients who used DOACs versus patients who used APT (OR, 0.58; 95% CI, 0.15-2.21; I2 = 41%) or no antithrombotic therapy (OR, 0.76; 95% CI, 0.20-2.86; I2 = 23%). ICH progression, risk of delayed ICH, and TBI-related in-hospital mortality were comparable among treatment groups. The present study indicates that elderly patients using DOACs have a lower risk of adverse outcome compared to patients using VKAs and a similar risk compared to patients using APT after mTBI.
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Journal of neurotrauma · Apr 2022
ReviewA Framework to Advance Biomarker Development in the Diagnosis, Outcome Prediction, and Treatment of Traumatic Brain Injury.
Multi-modal biomarkers (e.g., imaging, blood-based, physiological) of unique traumatic brain injury (TBI) endophenotypes are necessary to guide the development of personalized and targeted therapies for TBI. Optimal biomarkers will be specific, sensitive, rapidly and easily accessed, minimally invasive, cost effective, and bidirectionally translatable for clinical and research use. For both uses, understanding how TBI biomarkers change over time is critical to reliably identify appropriate time windows for an intervention as the injury evolves. ⋯ Prognostic biomarkers that reliably predict outcomes and recovery windows to assess neurodegenerative change and guide decisions for return to play or duty are also important. TBI biomarkers that fill these needs will transform clinical practice and could reduce the patient's risk for long-term symptoms and lasting deficits. This article summarizes biomarkers currently under investigation and outlines necessary steps to achieve short- and long-term goals, including how biomarkers can advance TBI treatment and improve care for patients with TBI.