Articles: traumatic-brain-injuries.
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Journal of neurotrauma · Apr 2023
LDC7559 Exerts Neuroprotective Effects by Inhibiting GSDMD-dependent Pyroptosis of Microglia in Mice with Traumatic Brain Injury.
Abstract Pyroptosis is considered one of a critical factor in the recovery of neurological function following traumatic brain injury. Brain injury activates a molecular signaling cascade associated with pyroptosis and inflammation, including NLRP3, inflammatory cytokines, caspase-1, gasdermin D (GSDMD), and other pyroptosis-related proteins. In this study, we explored the neuroprotective effects of LDC7559, a GSDMD inhibitor. ⋯ The findings revealed that inflammation and pyroptosis levels were decreased by LDC7559 or si-GSDMD treatment both in vitro and in vivo. Immunofluorescence staining, brain water content, hematoxylin and eosin staining, and behavioral investigations suggested that LDC7559 or si-GSDMD inhibited microglial proliferation, ameliorated cerebral edema, reduced brain tissue loss, and promoted brain function recovery. Taken together, LDC7559 may inhibit pyroptosis and reduce inflammation by inhibiting GSDMD, thereby promoting the recovery of neurological function.
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Traumatic brain injury (TBI) and Alzheimer's disease (AD) represent 2 of the largest sources of death and disability in the United States. Recent studies have identified TBI as a potential risk factor for AD development, and numerous reports have shown that TBI is linked with AD associated protein expression during the acute phase of injury, suggesting an interplay between the 2 pathologies. The inflammasome is a multi-protein complex that plays a role in both TBI and AD pathologies, and is characterized by inflammatory cytokine release and pyroptotic cell death. ⋯ Additionally, multiple genetic mutations associated with AD development alter microglia inflammatory activity, increasing and perpetuating inflammatory cell damage. In this review, we discuss the pathologies of TBI and AD and how they are impacted by and potentially interact through inflammasome activity and signaling proteins. We discuss current clinical trials that target the inflammasome to reduce heightened inflammation associated with these disorders.
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Journal of neurotrauma · Apr 2023
ReviewThe effect of Pre-management Antithrombotic Agent Use on Outcome following Traumatic Acute Subdural Haematoma in the Elderly: A Systematic Review.
Traumatic acute subdural hematomas (ASDH) are common in elderly patients (age ≥65 years) and are associated with a poorer prognosis compared with younger populations. Antithrombotic agent (ATA) use is also common in the elderly; however, the influence that pre-morbid ATA has on outcome in ASDH is poorly understood. We hypothesized that pre-morbid ATA use significantly worsens outcomes in elderly patients presenting with traumatic ASDH. ⋯ Reversal strategies, bridging therapy, recommencement of ATA, and comparison groups were poorly described; accordingly, our hypothesis was rejected. ATA reversal methods, identification of surgical candidates, optimal surgery methods, and when or whether ATA should be recommenced following ASDH resolution remain topics of debate. This study defines our current understanding on this topic, revealing clear deficiencies in the literature with recommendations for future research.
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Each year, approximately 70 million people suffer traumatic brain injury, which has a significant physical, psychosocial and economic impact for patients and their families. It is recommended in the UK that all patients with traumatic brain injury and a Glasgow coma scale ≤ 8 should be transferred to a neurosurgical centre. However, many patients, especially those in whom neurosurgery is not required, are not treated in, nor transferred to, a neurosurgical centre. ⋯ Analysis of the topics identified during the review was then summarised. These included: fundamental critical care management approaches (including ventilation strategies, fluid management, seizure control and osmotherapy); use of processed electroencephalogram monitoring; non-invasive assessment of intracranial pressure; prognostication; and rehabilitation techniques. Through this process, we have formulated practical recommendations to guide clinical practice in non-specialist centres.
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J Neurosurg Anesthesiol · Apr 2023
A Machine Learning Approach for Predicting Real-time Risk of Intraoperative Hypotension in Traumatic Brain Injury.
Traumatic brain injury (TBI) is a major cause of death and disability. Episodes of hypotension are associated with worse TBI outcomes. Our aim was to model the real-time risk of intraoperative hypotension in TBI patients, compare machine learning and traditional modeling techniques, and identify key contributory features from the patient monitor and medical record for the prediction of intraoperative hypotension. ⋯ This study developed a model for real-time prediction of intraoperative hypotension in TBI patients, which can use computationally efficient machine learning techniques and a streamlined feature-set derived from patient monitor data.