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
Observational StudyAssociation Between Early External Ventricular Drain Insertion And Functional Outcomes Six-months Following Moderate-to-Severe Traumatic Brain Injury.
Traumatic brain injury (TBI) is a leading global cause of morbidity and mortality. Intracranial hypertension following moderate-to-severe TBI (m-sTBI) is a potentially modifiable secondary cerebral insult and one of the central therapeutic targets of contemporary neurocritical care. External ventricular drain (EVD) insertion is a common therapeutic intervention used to control intracranial hypertension and attenuate secondary brain injury. ⋯ Following adjustment for the IMPACT (International Mission for Prognosis and Analysis of Clinical Trials in TBI) score extended (Core + CT), sex, injury severity score, study and treatment site, patients receiving a late EVD had higher odds of death or severe disability (GOSE 1-4) at 6 months follow-up than those receiving an early EVD adjusted odds ratio; 95% confidence interval, 2.14; 1.22-3.76; p = 0.008. Our study suggests that in patients with m-sTBI where an EVD is needed, early (≤ 24 h post-injury) insertion may result in better long-term functional outcomes. This finding supports future prospective investigation in this area.
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Journal of neurotrauma · Jun 2024
Evaluating Recovery After Two and Three Repeated Concussions Using Growth Curves.
The results of prior research concerning the effects of repeated concussions have been mixed. The aim of this study was to evaluate how concussion outcomes and presentation changed within patients who were evaluated at a concussion specialty clinic multiple times with a concussion. Subjects included 202 patients (54% male) aged 10-21 years (M = 13.17) who presented to a specialty concussion clinic for two and three concussions (77% sport-related) and were followed through formal clearance. ⋯ More severe presentation (i.e., days to recovery; higher symptom score) was significantly associated (-.62, p = 0.005) with greater improvement in recovery time (-.62, p = 0.005) and symptom burden (-.56, p < 0.001) at subsequent injuries. No covariates were significantly associated with improvement (or lack thereof) at subsequent injuries. This study adds to evidence suggesting multiple injuries is not associated with protracted recovery at subsequent injuries, in the context of treatment and full clearance for each injury at a multi-disciplinary clinic.