scholarly journals Brain Hypothermic Therapy Dramatically Decreases Elevated Blood Concentrations of High Mobility Group Box 1 in Neonates with Hypoxic-Ischemic Encephalopathy

2013 ◽  
Vol 35 ◽  
pp. 327-330 ◽  
Author(s):  
Toshihiko Nakamura ◽  
Shingo Yamada ◽  
Toshirou Yoshioka

Background. According to the Consensus 2010 of the International Liaison Committee on Resuscitation (ILCOR), children with moderate to severe hypoxic-ischemic encephalopathy (HIE) should receive brain hypothermic therapy (BHT) after successful resuscitation. Elevated high mobility group box 1 (HMGB1) in the blood at the early stage of brain ischemia-reperfusion injury has been suggested to be involved in the release of various inflammatory cytokines.Methods. In total, 21 neonates plasma HMGB1 concentration was measured. These neonates included 8 with HIE in whom BHT was indicated, 5 controls diagnosed as having HIE but who were not suitable candidates for BHT, and 8 normal controls.Results. The umbilical artery HMGB1 (UA-HMGB1) level before undergoing BHT significantly exceeded reference values. The UA-HMGB1 level in the BHT (−) group did not differ significantly from reference values, but was significantly increased 24 hours after birth. Repeated measure ANOVA showed a significant difference in time course changes between the BHT (+) and BHT (−) groups (P=0.0002).Conclusions. This study demonstrated hypothermic therapy to significantly decrease HMGB1. Furthermore, HMGB1 is a useful index of the inhibition of early stage inflammation.

2021 ◽  
Vol 18 ◽  
Author(s):  
Guang Yang ◽  
Zhimin Xue ◽  
Yuan Zhao

Background: MiR-582-5p has been demonstrated to protect against ischemic stroke. However, its implication in the progression of neonatal hypoxic-ischemic encephalopathy (HIE) has not been explored. Methods: In this study, we used an in vitro model of oxygen-glucose deprivation (OGD) to investigate the protective effect of miR-582-5p on PC12 cells. OGD-induced inhibition of cell viability and promotion of cell death was assessed by CCK-8 assay and flow cytometry. Real-time PCR and enzyme-linked immunosorbent assay (ELISA) were utilized to examine the levels of inflammatory cytokines. The effects of miR-582-5p on OGD-induced oxidative injury were assessed by the determination of oxidative stress indicators. Furthermore, dual-luciferase reporter assay and gain-offunction assay were used to determine the mechanism of miR-582-5p in OGD-induced cell injury. Results : The expression of miR-582-5p was reduced upon OGD treatment in PC12 cells. Overexpression of miR-582-5p inhibited OGD-induced PC12 cell injury by regulating cell viability, apoptosis, inflammatory responses, and oxidative stress. MiR-582-5p targeted and negatively regulated high mobility group box 1 (HMGB1). MiR-582-5p presented protective effects on OGD-induced PC12 cell injury by targeting HMGB1. Conclusion: Our results indicated that miR-582-5p ameliorates neuronal injury by inhibiting apoptosis, inflammation, and oxidative stress through targeting HMGB1.


2021 ◽  
Author(s):  
Osman Baştuğ ◽  
Bahadır İnan ◽  
Ahmet Özdemir ◽  
Binnaz Çelik ◽  
Funda Baştuğ ◽  
...  

Abstract Background: Hypocalcemia, hypomagnesemia, and hyperphosphatemia are common electrolyte disturbances in perinatal asphyxia(PA). Different reasons have been proposed for these electrolyte disturbances. This study investigated the effect of the urinary excretion of calcium(Ca), magnesium(Mg), and phosphorus(P) on the serum levels of these substances in babies who were treated using therapeutic hypothermia for hypoxic ischemic encephalopathy(HİE) caused by PA. This study sheds light on the pathophysiology that may cause changes in the serum values of these electrolytes.Method: This study included 21 healthy newborns(control group) and 38 patients(HİE group) who had undergone therapeutic hypothermia due to HİE. Only infants with a gestational age of 36 weeks and above and a birth weight of 2000 g and above were evaluated. The urine and serum Ca, Mg, P, and creatinine levels of all infants were evaluated at 24, 48, and 72 hours.Results: The lower serum Ca value and the higher serum P value of the HİE group were found to be statistically significant compared to the control group. There was no significant difference in serum Mg values between the groups. However, hypomagnesemia was detected in five patients from the HİE group. The urine excretions of these substances, which were checked at different times, were found to be significantly higher in the HİE group compared to the control group.Conclusion: This study determined that the urinary excretion of Ca, Mg, and P has an effect on the serum Ca, Mg, and P levels of infants with HİE.


2021 ◽  
Author(s):  
Kim-Ling Chin ◽  
Nurhafiza binti Zainal ◽  
Sing-Sin Sam ◽  
Pouya Hassandarvish ◽  
Rafidah Lani ◽  
...  

Abstract Neonatal microcephaly and adult Guillain-Barré syndrome are severe complications of Zika virus (ZIKV) infection. The robustly induced inflammatory cytokine expressions in ZIKV-infected patients may constitute a hallmark for severe disease. In the present study, the potential role of high mobility group box 1 protein (HMGB1) in ZIKV infection was investigated. HMGB1 protein expression was determined by the enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. HMGB1’s role in ZIKV infection was also explored using treatment with dexamethasone, an immunomodulatory drug. Antiviral effects of dexamethasone treatment on both wild-typed (WT) and HMGB1-knockdown (shHMGB1) Huh7 cells were determined by the focus-forming assay. Results showed that the Huh7 cells were highly susceptible to ZIKV infection. The infection was found to induce HMGB1 nuclear-to-cytoplasmic translocation, resulting in a >99% increase in the cytosolic HMGB1 expression at 72h.p.i. The extracellular HMGB1 level was elevated in a time- and multiplicity of infection (MOI)- dependent manner. Dexamethasone 150 µM treatment of the ZIKV-infected cells reduced HMGB1 extracellular release in a dose-dependent manner, with a maximum reduction of 71 ± 5.84% (p < 0.01). The treatment also reduced virus titers by over 83 ± 0.50% (p < 0.01). The antiviral effects, however, was not observed in the dexamethasone-treated HMGB1-knockdown cells, suggesting the importance of the intracellular HMGB1 in ZIKV infection. Overall, these results suggest that translocation of HMGB1 occurred during ZIKV infection and inhibition of the translocation reduced ZIKV replication. These findings highlight the potential of developing therapeutics against ZIKV infection by affecting the translocation of HMGB1 from the nucleus to the cytoplasm.


2021 ◽  
Vol 15 ◽  
Author(s):  
Bowen Weng ◽  
Chongbing Yan ◽  
Yihuan Chen ◽  
Xiaohui Gong ◽  
Cheng Cai

Background: To evaluate the safety and neurological outcomes of therapeutic hypothermia to neonatal hypoxic-ischemic encephalopathy (HIE).Materials and Methods: Medical records of 61 neonates with moderate to severe HIE were retrospectively enrolled and divided into a therapeutic hypothermia group (n = 36) and conventional therapy group (n = 25).Results: No significant difference in the incidence of severe adverse events was found between the two groups. Minimum and maximum voltages of amplitude-integrated electroencephalography (aEEG) recording results showed statistically significant differences in therapeutic hypothermia group after 72 h. The neonatal behavioral neurological assessment (NBNA) on the 28th day after birth and Bayley Scales of Infant Development, second edition (BSID II) scores at 18 months old were significant higher in the therapeutic hypothermia group than the conventional therapy group.Conclusion: Therapeutic hypothermia for neonates with moderate to severe HIE improved the development of the nervous system in 0–18-month-old infants and showed a predominant role in reducing death and major neuron development-associated disabilities.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Huan-Liang Wang ◽  
Yan-Qiu Xing ◽  
Ying-Xue Xu ◽  
Fei Rong ◽  
Wei-Fu Lei ◽  
...  

Lidocaine, a common local anesthetic drug, has anti-inflammatory effects. It has demonstrated a protective effect in mice from septic peritonitis. However, it is unknown whether lidocaine has effects on high mobility group box 1 (HMGB1), a key mediator of inflammation. In this study, we investigated the effect of lidocaine treatment on serum HMGB1 level and HMGB1 expression in liver, lungs, kidneys, and ileum in septic rats induced by cecal ligation and puncture (CLP). We found that acute organ injury induced by CLP was mitigated by lidocaine treatment and organ function was significantly improved. The data also demonstrated that lidocaine treatment raised the survival of septic rats. Furthermore, lidocaine suppressed the level of serum HMGB1, the expression of HMGB1, and the activation of NF-κB p65 in liver, kidneys, lungs, and ileum. Taken together, these results suggest that lidocaine treatment exerts its protective effection on CLP-induced septic rats. The mechanism was relative to the inhibitory effect of lidocaine on the mRNA expression level of HMGB1 in multiple organs, release of HMGB1 to plasma, and activation of NF-κB.


Author(s):  
Khalid S. Salih ◽  
Farqad B. Hamdan ◽  
Qasim S. Al-Mayah

Abstract Introduction There are large numbers of inflammatory molecules and humoral mediators that can be involved in the epileptogenesis such as cytokines, matrix metalloproteinases (MMP), and high mobility group box-1 (HMGB1). We aimed to evaluate serum levels and the diagnostic value of MMP-2 and HMGB1 in Iraqi patients with epilepsy. Methods One hundred epileptic patients comprised 60 controlled epileptics and 40 refractory patients to treatment with multi antiepileptic drugs (AEDs). Other 50 family-unrelated age- and sex-matched healthy subjects were selected to represent the control group. Serum levels of MMP-2 and HMGB1 were estimated using ELISA. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of these markers when required. Results MMP-2 level was significantly higher in controls than epileptic patients in general (controlled and refractory patients). ROC curve, showed poor diagnostic value of MMP-2 in discriminating epileptics into responsive or refractory to treatment from controls (AUC = 0.679 (95% CI = 0.536-0.823), and AUC = 0.77 (95% CI = 0.637-902), respectively). Serum HMGB1 level in epileptic patients and controls was in close approximation to each other. Conclusions MMP-2 is significantly decreased in patients particularly those with refractory epilepsy (RE); however, it has poor diagnostic value. No difference in the serum HMGB1 level between epileptic patients and controls.


Author(s):  
Fatma Ibrahim Soliman Elshal ◽  
Walid Ahmed Elshehaby ◽  
Mahmoud Abd elaziz Dawoud ◽  
Ekhlas Abdelmonem Shaban

Abstract Background Hypoxic ischemic encephalopathy is a major cause of pediatric mortality and morbidity, with possible long-term neurologic sequel, such as cerebral palsy. With improvements in care of at-risk neonates, more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. The aim of the study was to assess the additive role of magnetic resonance spectroscopy over conventional MRI in diagnosis and early prediction of pathological motor development in neonates with hypoxic ischemic encephalopathy. Results MRS ratios showed significant difference between unfavorable and normal outcome infants. MRS ratios as Lac/Cr, NAA/Cr and NAA/Cho within basal ganglia, thalamus and white matter can significantly differentiate between patients with normal and pathological outcome at 1 year. Lac/Cr positively correlates with the severity of HIE. Both NAA/Cr and NAA/Cho negatively correlate with the severity of the disease. Ratios cutoff values as Lac/Cr above 0.38 and 0.42 in basal ganglia and white matter, respectively, NAA/Cr below 0.9 and 0.8 in basal ganglia and occipital white matter, respectively, and NAA/Cho below 0.29 and 0.31 in basal ganglia and frontal white matter, respectively, were significantly predictive of pathological outcome. Conclusion High Lac/Cr, low NAA/Cr and low NAA/Cho ratios within examined regions of the brain including deep grey matter nuclei as well as white matter are associated with an adverse outcome in infants with perinatal asphyxia. MRS is an accurate quantitative MR biomarker within the neonatal period for prediction of neurodevelopmental outcome after perinatal HIE. MRS may be useful in early clinical management decisions, and counseling parents thereby ensuring appropriate early intervention and rehabilitation.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Yan Lin ◽  
Lian-Jie Lin ◽  
Yu Jin ◽  
Yong Cao ◽  
Ying Zhang ◽  
...  

Background. Aberrant expression of high mobility group box-1 protein (HMGB1) contributes to the progression of various inflammatory diseases. This meta-analysis focused on the clinical significance of serum HMGB1 levels in pancreatitis patients, with the goal of building a novel diagnostic score model.Method. We conducted a meta-analysis by searching in the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases without any language restrictions. Studies were pooled and standard mean difference (SMD) and its corresponding 95% confidence intervals (95% CIs) were calculated. Version 12.0 STATA software was used for statistical analysis.Results. We performed a final analysis of 841 subjects from 12 clinical case-control studies. The meta-analysis results showed a positive association between serum HMGB1 levels and the progression of pancreatitis. In the subgroup analysis by country, high serum level of HMGB1 may be related to pancreatitis progression in China, Korea, Hungary, and Japan populations (allP<0.05).Conclusion. The present meta-analysis indicated that serum HMGB1 level was statistically elevated in patients with pancreatitis, and thus serum levels of HMGB1 could be determined to be a useful biomarker for pancreatitis patients.


2016 ◽  
Vol 23 (3) ◽  
pp. 266-273 ◽  
Author(s):  
Nafisa H. R. AbdelAziz ◽  
Hanan G. AbdelAzeem ◽  
Eman M. M. Monazea ◽  
Tahra Sherif

Background: The incidence of neonatal hypoxic–ischemic encephalopathy (HIE) is reportedly high in countries with limited resources. Its pathogenesis is multifactorial. A role for thrombophilia has been described in different patterns of preterm and full-term perinatal brain injury. Aim: This study aims to identify risk factors associated with neonatal HIE and also to determine the contributions of genetic thrombophilia in the development of neonatal HIE. Methods: Sixty-seven neonates with HIE and 67 controls were enrolled in the study. Clinical history and examination were undertaken. Patients and controls were tested for the presence of factor V G1691A and prothrombin G20210A mutations. In addition, protein S, protein C, and antithrombin III levels were assessed. Results: Parental consanguinity and performing emergency cesarean section (CS) were significant risk factors for neonatal HIE (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.6-15.3, P < .001, OR 12.6, 95% CI 2.52-63.3, P = .002, respectively). No significant difference was found regarding maternal age and parity. About 33% of cases and 6% of controls were found to have at least 1 thrombophilic factor ( P < .001). Factor V G1691A mutation significantly increased the risk of neonatal HIE (OR 4.5, 95% CI 1.4-14.5, P = .012), while prothrombin G 20210A mutation and protein C deficiency were not. Conclusion: Parental consanguinity, emergency CS, and factor V mutation may contribute to the higher risk of developing neonatal HIE.


2019 ◽  
Vol 27 (4) ◽  
pp. 251-255 ◽  
Author(s):  
Necla Benlier ◽  
Mustafa Bilge Erdoğan ◽  
Serdar Keçioğlu ◽  
Nuri Orhan ◽  
Hülya Çiçek

Background Recently, the role of inflammation in coronary artery disease and the association of inflammatory biomarkers with adverse outcomes have been investigated in many studies. We investigated the relationship between high serum mobility group box 1 protein levels and established risk factors for coronary artery disease. Methods Fifty-five patients who presented to our Cardiovascular Surgery Clinic and subsequently underwent coronary artery bypass surgery for coronary artery disease and 50 healthy subjects presenting to the cardiology outpatient clinic without any cardiovascular problem were included in the study. The mean age was 61.47 ± 9.38 years for patients and 58.20 ± 10.15 years for controls. Results There was no statistically significant difference between groups with respect to age or sex. Family history of coronary artery disease, aspirin use, hypertension, and type 2 diabetes were significantly more prevalent in the patient group versus the control group. A significant difference was found between patients and healthy controls with respect to high mobility group box 1 protein levels ( p = 0.001). Conclusions Serum high mobility group box 1 protein was significantly increased in patients with coronary artery disease in comparison to healthy subjects. No associations were found between high mobility group box 1 protein level and certain risk factors for coronary artery disease.


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