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Expression of high mobility group B1 and toll-like receptor-nuclear factor ?B signaling pathway in chronic subdural hematomas.

ABSTRACT: Chronic subdural hematoma (CSDH) is an angiogenic and inflammatory disease. Toll-like receptors (TLRs) transduce intracellular signals, resulting in the activation of nuclear factor ?B (NF-?B), which leads to the production of inflammatory cytokines. High-mobility group box 1 (HMGB1) functions as a mediator of inflammatory responses through TLRs. In this study, we examined the expression of HMGB1 and components of the Toll-like receptor and NF-?B signaling pathways in the outer membrane of CSDH. Eight patients whose outer membrane was successfully obtained during trepanation surgery were included in this study. The expression of TLR4, myeloid differentiation factor 88 (MyD88), interleukin-1 receptor-associated kinase 4 (IRAK4), TNF receptor-associated factor 6 (TRAF6), TGF?-activated kinase 1 (Tak1), interferon regulatory factors 3 (IRF3), I?B kinase ? (IKK?), IKK?, I?B?, I?B?, NF-?B/p65 and ?-actin was examined by Western blot analysis. The expression of TLR4, NF-?B/p65 and interleukin-6 (IL-6) was also examined by immunohistochemistry. The concentrations of HMGB1 and IL-6 in CSDH fluids were measured using ELISA kits. Above-mentioned molecules were detected in all cases. In addition, TLR4, NF-?B/p65 and IL-6 were localized in the endothelial cells of vessels within CSDH outer membranes. The concentrations of HMGB1 and IL-6 in CSDH fluids were significantly higher than that in the CSF and serum. There existed a correlation between the concentrations of HMGB1 and IL-6 in CSDH fluids. Our data suggest that HMGB1 in CSDH fluids produces the inflammatory cytokine IL-6 in endothelial cells through the Toll-like receptor and NF-?B signaling pathways. Anti-HMGB1 therapy might be a useful method to treat the growth of CSDH.

SUBMITTER: Osuka K

PROVIDER: S-EPMC7263617 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Expression of high mobility group B1 and toll-like receptor-nuclear factor κB signaling pathway in chronic subdural hematomas.

Osuka Koji K Watanabe Yasuo Y Usuda Nobuteru N Iwami Kenichiro K Miyachi Shigeru S Takayasu Masakazu M

PloS one 20200601 6

Chronic subdural hematoma (CSDH) is an angiogenic and inflammatory disease. Toll-like receptors (TLRs) transduce intracellular signals, resulting in the activation of nuclear factor κB (NF-κB), which leads to the production of inflammatory cytokines. High-mobility group box 1 (HMGB1) functions as a mediator of inflammatory responses through TLRs. In this study, we examined the expression of HMGB1 and components of the Toll-like receptor and NF-κB signaling pathways in the outer membrane of CSDH. ...[more]

PMID: 32479555

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Project description:Objective: This study aimed to evaluate the correlation between arachnoid cysts and chronic subdural hematomas in young adults. Methods: This retrospective study evaluated ten patients having concomitant chronic subdural hematomas and arachnoid cysts. Patients were evaluated with the data of age and gender, location of hematoma and arachnoid cyst, trauma history, symptoms at admission, maximum hematoma diameter, contiguity between arachnoid cyst and hematoma, and treatment methods. Results: We treated 285 patients who were diagnosed with cSDH between January 2013 and December 2019. 22 patients were under the age of 40 years. Ten of them had both cSDH and arachnoid cysts. The mean age of patients was 24.8±3.9 years. Patients with only chronic subdural hematoma had higher mean age than the patients with arachnoid cyst-related chronic subdural hematoma. In four patients, the onset of chronic subdural hematoma was reported after arachnoid cyst diagnosis. Four of the patients did not have causative trauma history, and two patients suffered minor sports-related traumas. All patients had headache, and only two patients had hemiparesis. The location of arachnoid cysts were in the middle fossa in eight patients. All patients had chronic subdural hematomas on the ipsilateral side of arachnoid cyst. Four patients who had smaller than 10 mm maximal cSDH diameter underwent conservative management. They were followed by serial neuroimaging studies and it was noted that the hematoma disappered and the size of the arachnoid cysts decreased over time without any neurological complication. In six cases, craniotomy was required, and all recovered completely. cSDH did not recur during 5-60 months of follow-up period (median 12 months). Conclusions: It seems that presence of an arachnoid cyst in young adults is a predisposing factor for the formation of chronic subdural hematoma. Coincidentally diagnosed arachnoid cyst patients may be followed up with periodical clinical examinations and neuroimaging studies.

Project description:Background: The possible influence of different antithrombotic drugs on outcome after neurosurgical treatment of chronic subdural hematoma (CSDH) is still unclear. Nowadays, no randomized clinical trials are available. A metanalysis including 24 studies for a total of 1,812 pooled patients concluded that antiplatelets and anticoagulations present higher risk of recurrences. On the other hand, several studies highlighted that antithrombotic suspension, timing of surgery, and resumption of these drugs are still debated, and patients taking these present higher risk of thromboembolic events with no excess risk of bleed recurrences or worse functional outcome. Our assumption is that the real hemorrhagic risk related to antithrombotic drug continuation in CSDH may be overrated and the thromboembolic risk for discontinuation underestimated, especially in patients with high cardiovascular risk. Methods: A comprehensive literature review with the search terms "acetylsalicylic acid" and "chronic subdural x" was performed. Clinical status, treatment, time of drug discontinuation, complications (in particular, rebleeding or thromboembolic events), and clinical and radiological outcome at follow-up were evaluated. Results: Five retrospective studies were selected for the review, three of them reporting specifically low-dose acetylsalicylic intake and two of them general antithrombotic drugs for a total of 1,226 patients. Only two papers reported the thromboembolic rate after surgery; in one paper, it is not even divided from other cardiac complications. Conclusion: The literature review does not clarify the best management of low-dose acetylsalicylic in CSDH patients, in particular, concerning the balance between thromboembolic event rates and rebleeding risks. We do believe that CSDH precipitates the worsening of comorbidities with a resulting increased mortality. Further studies clearly evaluating the thromboembolic events are strongly needed to clarify this topic. In this perspective paper, we discuss the difficult choice of low-dose acetylsalicylic acid (LDAA) management in patients suffering from chronic subdural hematoma (CSDH). The balance between hemorrhagic and thromboembolic risks often represents a sword of Damocles for neurosurgeons, especially when dealing with patients with high cardiovascular risk. No guidelines are currently available, and a survey by Kamenova et al. showed that most neurosurgeons discontinue LDAA treatment for at least 7 days in the perioperative period of surgical evacuation of CSDH, even though recent studies show that early LDAA resumption might be safe. Thrombosis prophylaxis is administered by only 60%, even though patients with CSDH are at high risk of developing thromboembolic complications. We would like to bring attention to this controversial issue.

Project description:Chronic subdural hematoma (CSDH) is one of the most frequent reason for cranial neurosurgical consultation. There is no widely accepted medical treatment for this condition. Herein, we present the protocol for the Tranexamic Acid (TXA) in Chronic Subdural Hematomas (TRACS) trial aiming at determining whether TXA can increase the rate of CSDH resolution following conservative management, lower the number of required surgical procedures and decrease the rate of CSDH recurrence following surgical evacuation.TRACS is a multicenter, double-blind, randomized, parallel-design, placebo-controlled, phase IIB study designed to provide preliminary efficacy data as well as feasibility, safety and incidence data required to plan a larger definitive phase III trial. Consecutive patients presenting with a diagnosis of chronic subdural hematoma will be screened for eligibility. Exclusion criteria include: specific risk factors for thromboembolic disease, anticoagulant use or contraindication to TXA. A total of 130 patients will be randomized to receive either 750 mg of TXA daily or placebo until complete radiological resolution of the CSDH or for a maximum of 20 weeks. CSDH volume will be measured on serial computed tomography (CT) scanning. Cognitive function tests, quality of life questionnaires as well as functional autonomy assessments will be performed at enrollment, at 10 weeks following randomization and at 3 months following treatment cessation. During the treatment period, patients will undergo standard CSDH management with surgery being performed at the discretion of the treating physician. If surgery is performed, the CSDH and its outer membrane will be sampled for in vitro analysis. The primary outcome is the rate of CSDH resolution by 20 weeks without intervening unplanned surgical procedure. Secondary outcomes include: CSDH volume, incidence of surgical evacuation procedures, CSDH recurrence, cognitive functions, functional autonomy, quality of life, incidence of complications and length of hospital stay. Planned subgroup analyses will be performed for conservatively versus surgically managed subjects and highly versus poorly vascularized CSDH.CSDH is a frequent morbidity for which an effective medical treatment has yet to be discovered. The TRACS trial will be the first prospective study of TXA for CSDH.NCT ID: NCT02568124 .

Project description:The elderly population are at high risk for developing chronic subdural hematoma (cSDH). Surgical evacuation of cSDH is one of the most common procedures performed in neurosurgery. The present study aims to identify potential inflammatory biomarkers associated with its development and recurrence. Patients (>65 years of age) who presented with symptomatic cSDH (≥1 cm thickness or ≥5 mm midline shift [MLS]), requiring surgical intervention, were prospectively enrolled. The collected cSDH fluid was analyzed for inflammatory markers. Computed tomography (CT) scan data included pre-operative cSDH thickness and MLS. Outcome data included Glasgow Outcome Scale-Extended (GOS-E) score at 3, 6, and 12 months post-surgery, as well as cSDH recurrence. A decision tree model was used to determine the predictive power of extracted analytes for MLS, cSDH thickness, and recurrence. This pilot study includes 20 enrolled patients (mean age 77.9 ± 7.4 years and 85% falls). Rate of cSDH recurrence was 42%, with 21% requiring reoperation. Chemokine (C-X-C motif) ligand 9 (CXCL9) concentrations correlated with cSDH thickness (r = 0.975, p = 0.040). Interleukin (IL)-6 and vascular endothelial growth factor (VEGF)-A concentrations correlated with MLS (r = 0.974, p = 0.005; r = 0.472, p = 0.036, respectively). IL-5 concentrations correlated with more favorable GOS-E scores at 3, 6, and 12 months (r = 0.639, p = 0.006; r = 0.727, p = 0.003; r = 0.693, p = 0.026, respectively). Regulated on activation, normal T-cell expressed and secreted (RANTES) concentrations correlated with complete cSDH resolution (r = 0.514, p = 0.021). The decision tree model identified that higher concentrations of CXCL9 were predictive of MLS (risk ratio [RR] = 12.0), higher concentrations of IL-5 were predictive of cSDH thickness (RR = 4.5), and lower concentrations of RANTES were predictive of cSDH recurrence (RR = 2.2). CXCL9, IL-6, VEGF, IL-5, and RANTES are associated with recurrence after surgery and may be potential biomarkers for predicting cSDH recurrence and neurological outcomes.

Project description:BackgroundAntithrombotic-associated subdural hematomas (SDHs) are increasingly common, and the possibility of clinical deterioration in otherwise stable antithrombotic-associated SDH patients may prompt unnecessary admissions to intensive care units. It is unknown whether all antithrombotic regimens are equally associated with the need for critical care interventions. We sought to compare the frequency of critical care interventions and poor functional outcomes among three cohorts of noncomatose SDH patients: patients on no antithrombotics, patients on anticoagulants, and patients on antiplatelets alone.MethodsWe performed a retrospective cohort study on all noncomatose SDH patients (Glasgow Coma Scale > 12) presenting to an academic health system in 2018. The three groups of patients were compared in terms of clinical course and functional outcome. Multivariable logistic regression was used to determine predictors of need for critical care interventions and poor functional outcome at hospital discharge.ResultsThere were 281 eligible patients presenting with SDHs in 2018, with 126 (45%) patients on no antithrombotics, 106 (38%) patients on antiplatelet medications alone, and 49 (17%) patients on anticoagulants. Significant predictors of critical care interventions were coagulopathy (OR 5.1, P < 0.001), presence of contusions (OR 3, P = 0.007), midline shift (OR 3.4, P = 0.002), and maximum SDH thickness (OR 2.4, P = 0.002). Significant predictors of poor functional outcome were age (OR 1.8, P < 0.001), admission Glasgow Coma Scale score (OR 0.3, P < 0.001), dementia history (OR 4.2, P = 0.001), and coagulopathy (OR 3.5, P = 0.02). Isolated antiplatelet use was not associated with either critical care interventions or functional outcome.ConclusionIsolated antiplatelet use is not a significant predictor of need for critical care interventions or poor functional outcome among SDH patients and should not be used as a criterion for triage to the intensive care unit.

Dataset Information

Expression of high mobility group B1 and toll-like receptor-nuclear factor ?B signaling pathway in chronic subdural hematomas.

Publications

Expression of high mobility group B1 and toll-like receptor-nuclear factor κB signaling pathway in chronic subdural hematomas.

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