Journal of neurotrauma
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Journal of neurotrauma · Jun 2024
Susceptibility to Hepatotoxic Drug-induced Liver Injury Increased after Traumatic Brain Injury in Mice.
The early stages of brain injury can induce acute liver injury, which can be recovered in the short term. Continued medication treatment during hospitalization for brain injury alleviates the prognosis and contributes to a high incidence of drug-induced liver injury (DILI). We hypothesize that there is an interaction between changes in the hepatic environment after brain injury and liver injury produced by intensive drug administration, leading to an upregulation of the organism's sensitivity to DILI. ⋯ All mice were divided into four groups: Sham, TBI, APAP, and TBI+APAP, and related liver injury indicators in liver and serum were detected by Western blot, Quantitative real-time PCR (qRT-PCR), and immunohistochemical staining. The results suggested that liver injury induced in the early stages of brain injury recovered in 3 days, but this state could still significantly aggravate DILI, represented by higher liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), oxidative stress (increase in malondialdehyde [MDA] concentration and deregulation of glutathione [GSH] and superoxide dismutase [SOD] activities), inflammatory response (activation of the HMGB1/TLR4/NF-κB signaling pathway, and increased messenger RNA [mRNA] and protein levels of pro-inflammatory cytokines including tumor necrosis factor alpha [TNF-α], interleukin [IL]-6, and IL-1β), and apoptosis (TUNEL assay, upregulation of Bax protein and deregulation of Bcl-2 protein). In summary, our results suggested that TBI is a potential susceptibility factor for DILI and exacerbates DILI.
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Journal of neurotrauma · Jun 2024
MCC950 attenuates microglial NLRP3-mediated chronic neuroinflammation and memory impairment in a rat model of repeated low-level blast exposure.
Blast-induced traumatic brain injury is typically regarded as a signature medical concern for military personnel who are exposed to explosive devices in active combat zones. However, soldiers as well as law enforcement personnel may be repeatedly exposed to low-level blasts during training sessions with heavy weaponries as part of combat readiness. Service personnel who sustain neurotrauma from repeated low-level blast (rLLB) exposure do not display overt pathological symptoms immediately but rather develop mild symptoms including cognitive impairments, attention deficits, mood changes, irritability, and sleep disturbances over time. ⋯ Animals exposed to rLLB displayed acute and chronic short-term memory impairments and chronic anxiety-like symptoms accompanied by increased microglial activation, NLRP3 expression, and IL-1β release. Treatment with MCC950, an NLRP3 inflammasome complex inhibitor, suppressed microglial activation, reduced NLRP3 expression and IL-1β release, and improved short-term memory deficits after rLLB exposure. Collectively, this study demonstrates that rLLB induces chronic neurobehavioral and neuropathological changes by increasing NLRP3 inflammasome protein expression followed by cytokine IL-1β release.
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Journal of neurotrauma · Jun 2024
Cause of Concussion with Persisting Symptoms is Associated with Long-Term Recovery and Symptom Type, Duration, and Number in a Longitudinal Cohort of 600 Patients.
It is important for patients and clinicians to know the potential for recovery from concussion as soon as possible after injury, especially in patients who do not recover completely in the first month and have concussion with persisting concussion symptoms (C+PCS). We assessed the association between the causes of concussion and recovery from C+PCS in a consecutive retrospective and prospective cohort of 600 patients referred to the Canadian Concussion Center (CCC) at Toronto Western Hospital. Data were obtained from clinical records and follow-up questionnaires and not from a standardized database. ⋯ Significant differences among the four causes included age (p < 0.001), sex (p < 0.001), number of previous concussions (p < 0.001), history of psychiatric disorders (p = 0.002), and migraine (p = 0.001). Recovery from concussion was categorized into three groups: (1) Complete Recovery occurred in only 60 (10%) patients with median time 8.0 (IQR:3.5-18.0) months and included 42 S&R, 7 MVC, 8 falls, and 3 SBOV; (2) Incomplete Recovery occurred in 408 (68.0%) patients with persisting median symptom time of 5.0 (IQR:2.0-12.0) months; and (3) Unknown Recovery occurred in 132 (22.0%) patients and was because of lack of follow-up. In summary, the cause of C+PCS was associated with the type, number, and duration of symptoms and time required for recovery, although all causes of C+PCS produced prolonged symptoms in a large percentage of patients, which emphasizes the importance of concussions as a public health concern necessitating improved prevention and treatment strategies.
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Journal of neurotrauma · Jun 2024
Predicting Hematoma Expansion and Prognosis in Cerebral Contusions: A Radiomics-Clinical Approach.
Hemorrhagic progression of contusion (HPC) often occurs early in cerebral contusions (CC) patients, significantly impacting their prognosis. It is vital to promptly assess HPC and predict outcomes for effective tailored interventions, thereby enhancing prognosis in CC patients. We utilized the Attention-3DUNet neural network to semi-automatically segment hematomas from computed tomography (CT) images of 452 CC patients, incorporating 695 hematomas. ⋯ Selected radiomic features indicated that irregularly shaped and highly heterogeneous hematomas increased the likelihood of HPC, while larger weighted axial lengths and lower densities of hematomas were associated with a higher risk of poor prognosis. Predictive models that combine radiomic and clinical features exhibit robust performance in forecasting HPC and the risk of poor prognosis in CC patients. Radiomic features complement clinical features in predicting HPC, although their ability to enhance the predictive accuracy of the clinical model for adverse prognosis is limited.
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Journal of neurotrauma · Jun 2024
Applying the Sliding Scale Approach to Quantifying Functional Outcomes up to Two Years After Severe Traumatic Brain Injury.
Outcomes after severe traumatic brain injury (TBI) can be represented by a sliding score that compares actual functional recovery to that predicted by illness severity models. This approach has been applied in clinical trials because of its statistical efficiency and interpretability but has not been used to describe change in functional recovery over time. The objective of this study was to use a sliding scoring system to describe the magnitude of change in Glasgow Outcome Scale Extended (GOSE) score at 6, 12, and 24 months after severe TBI and to compare patients who improved after 6 months to those who did not. ⋯ Among those who improved at 12 months, the average magnitude of improvement was 1.7 ± 0.9 and among those who improved at 24 months, the average magnitude of improvement was 1.9 ± 1.0. Those who improved their GOSE-SS score from 6 to 24 months had longer hospital stays (mean-difference = 8.6 days; p = 0.03), longer intensive care unit (ICU) stays (mean-difference = 5.5 days; p = 0.02), and longer ventilator time (mean-difference = 5 days; p = 0.02) than those who worsened. These results support an optimistic long-term outlook for severe TBI patients and emphasize the importance of long-term follow-up in severe TBI survivors.