scholarly journals The Effects of Ionotropic GABA Receptor Blockage on Brain in Sepsis-induced Rats

Author(s):  
Gulten Ates ◽  
Elif Ozkok ◽  
Gul Ipek Gundogan ◽  
Sule Tamer

Abstract Encephalopathy develops following sepsis, which is defined as life-threatening organ failure due to the irregular response of a host to infection. It has high mortality and morbidity rates. In this study, we aimed to investigate the effects of inflammation on brain tissue, and the effects of the GABAA receptor antagonist bicuculline in rats with sepsis. Sepsis was experimentally generated in rats using LPS. The rats were divided into four groups as control, LPS (10 mg/kg i.p.), bicuculline (1.5 mg/kg bicuculline methiodide s.c.), and LPS + bicuculline. Electrophysiologic recordings and body temperature measurements were completed at the 24th hour after injection, and blood samples were taken from the heart for measurements of biochemical parameters. TNF-α, IL-10, and GABA levels were measured using ELISA, and MDA levels were measured using the Bouge method from brain tissue. Tissue imaging was performed with S100-ß, NEUN, and synaptophysin antibody using immunofluorescence staining. One-way ANOVA and the Tukey test were used in statistical analysis. Inflammatory parameters increased in brain tissue in the LPS group compared with the control group. The immunofluorescence staining results in brain tissues were as follows: S-100ß involvement increased, and NeuN and synaptophysin involvement decreased in the LPS group. In electrophysiologic recordings, activity consistent with acute non-focal seizures was observed in the LPS group; however, it was consistent with the resting status in other groups. We suggest that the GABAA antagonist bicuculline methiodide may be a prophylactic agent in sepsis, which caused the impaired neurotransmitter balance, increased pro-inflammatory cytokine and lipid peroxidation, and decreased anti-inflammatory cytokine levels.

2021 ◽  
Author(s):  
Tingmei Wu ◽  
Haiwen Li ◽  
Huixia Zhou ◽  
Xuemei Hao ◽  
Xiaojun Wang ◽  
...  

Abstract Objective: Enhanced recovery after surgery (ERAS) protocols are established in adults but not fully evaluated in children. This study investigated whether an ERAS protocol improved recovery and influenced postoperative inflammatory cytokine levels in children undergoing surgery for hydronephrosis. Methods: This randomized controlled study included patients who underwent robot-assisted laparoscopic surgery for hydronephrosis at Bayi Children's Hospital (Beijing, China) between October 2018 and September 2019. Patients were randomized to an ERAS group (perioperative ERAS protocol) or control group (standard perioperative management). Outcomes related to postoperative recovery and inflammatory cytokine levels were evaluated. Results: The final analysis included 18 patients in each group. Five patients (27.78%) in each group experienced postoperative complications (abdominal pain, nausea and vomiting, subcutaneous emphysema or fever). The ERAS group had a shorter time to first postoperative flatus than the control group (25 vs. 49 hours; P =0.009), although the time for abdominal drainage flow to reach ≤20 mL/day, time to urinary catheter removal and length of hospital stay did not differ significantly between groups. Preoperative plasma cytokine levels were comparable between groups. Compared with the control group, the ERAS group had a higher IL-6 level on postoperative day 2 ( P <0.05) and a lower concentration of IL-1β on postoperative days 1 and 2 ( P <0.05). Postoperative levels of CRP, TNFα and IL-10 did not differ significantly between groups. Conclusions: ERAS may accelerate postoperative recovery and modulate the postoperative inflammatory response in pediatric patients undergoing robot-assisted laparoscopic pyeloplasty for hydronephrosis.


2017 ◽  
Vol 45 (1) ◽  
pp. 5
Author(s):  
Deniz Uluisik ◽  
Ercan Keskin

Background: Coenzyme Q10 is a well-known cofactor in the mitochondrial electron transport chain required for ATP production. Coenzyme Q10 is recognized as an intracellular antioxidant that protects cell membrane phospholipids, mitochondrial membrane protein, and plasma low-density lipoprotein against oxidative damage caused by free radicals. Diabetes and its complications have been related to increased levels of free radicals and systemic proinflammatory cytokines and to an abnormal lipid profile. The aim of this study was to investigate the effects of coenzyme Q10 supplementation on some cytokine levels in streptozotocin-induced diabetic rats.Materials, Methods & Results: In this study, 38 healthy, adult male rats were used. The rats were divided into 5 groups. All animals were housed in separated cages during the four weeks. The animals in group 1 was fed standard rat pellets for 4 weeks. It was administered at 0.3 mL corn oil intraperitoneally daily for four weeks in group 2 animals. The animals in group 3 was injected intraperitoneally with 10 mg/kg CoQ10 daily for 4 weeks. Group 4 was made diabetic by subcutaneous injections of streptozotocin at dose of 40 mg/kg in 0.1 M citrate buffer (pH 4.5) single daily dose for two days and group 5 was made diabetic by subcutaneous injections of streptozotocin at dose of 40 mg/kg in 0.1 M citrate buffer (pH 4.5) single daily dose for two days and then was injected intraperitoneally with 10 mg/kg CoQ10 daily for 4 weeks. During the experiment, three animals from group 4 and one animals from group 5 were died due to streptozotocin-induced hypoglycemia. At the end of the study, blood samples were taken from all animals. In these blood samples, IL-4, IL-6, IL-10 and TNF-α plasma levels were determined with ELISA using sandwich enzyme-linked immunosorbent method via commercial kits. In this study, IL-4 level as an anti-inflammatory cytokine significantly decreased (P < 0.05) with diabetes induction compared to control group level. IL-10 level in diabetic group was statistically different (P < 0.05) from control group level. CoQ10 application to diabetic animals improved the falling in IL-10 level of diabetic group (P < 0.05). IL-6 and TNF-α levels in diabetic group significantly increased (P < 0.05) in parallel with each other compared to control group levels. The same parameters were reduced (P < 0.05) by CoQ10 application in diabetic animals.Discussion: In this study, the occurred changes in pro- and anti-inflammatory cytokines with experimentally induced diabetes are expected results and these results are consistent with some studies related diabetes. These results may be considered to hazardous effects and inflammation caused by diabetes on liver, pancreas and other tissues. CoQ10 suppressed the increments in plasma pro-inflammatory cytokine levels, whereas it restored the reducing in anti-inflammatory cytokine levels arising due to diabetes. The obtained results from this study after CoQ10 application supported similar studies used CoQ10 application against deleterious effects of diabetes in animals and humans. Therefore, it is possible to say that CoQ10 may play important role in regulation of imbalance between inflammation markers in diabetes conditions and further studies are needed to clear the beneficial effects of CoQ10 treatment on the other inflammation markers in diabetes status.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Kawther Aabed ◽  
Ramesa Shafi Bhat ◽  
Abeer Al-Dbass ◽  
Nadine Moubayed ◽  
Norah Algahtani ◽  
...  

Abstract Background Neuroinflammation plays a major role in the pathogenesis of autism because the cytokine levels are typically disturbed in the brain in autistic patients. Prebiotics-rich diet maintains the healthy gut microbiota and hence can regulate the neuroinflammation indirectly. The study aimed to investigate the role of bee pollen and propolis in ameliorating neuroinflammation, including cytokine levels, in an animal model of autism. Methods Hamsters were classified as four groups: Group I, control; Group II, autistic model/animals treated with 250 mg propionic acid (PPA)/kg body weight (BW)/day for 3 days; Group III, animals treated with bee pollen at a dose of 250 mg/kg BW/day for 4 weeks; and Group IV, animals treated with propolis at a dose of 250 mg/kg BW/day for 4 weeks. Neuroinflammatory responses were evaluated using the levels of interferon γ (IFN-γ), interleukin 1 alpha (IL-1α), IL-6, IL-10, IL-12 (p70), vascular endothelial growth factor (VEGF), and tumor necrosis factor α (TNFα). Results Significant decrease of IL-10 (P<0.026), VEGF (P<0.005), and TNFα(P<0.005) levels and increased IL-1α (P<0.032), IL-6(P<0.028), and IFN-γ (P<0.013) levels were observed between the four studied groups. The neurotoxic effects of PPA was clearly presented as much higher IL-6, as pro-inflammatory cytokine (P<0.05), concomitant with much lower IL-10, as anti-inflammatory cytokine(P<0.015) compared to controls. Both bee pollen and propolis were effective in ameliorating the neurotoxic effects of PPA demonstrating non-significant changes of IL-6 and IL-10 when compared to control healthy hamsters. Conclusions Our findings indicate that both bee pollen and propolis protect against neuroinflammation in the rodent model of autism. However, further studies are needed to investigate the clinical benefits of prebiotics-rich diet in neurodevelopmental disorders, such as autism.


2021 ◽  
Vol 8 (7) ◽  
pp. 2037
Author(s):  
Girish K. Madhavan ◽  
Philip Issac ◽  
Balakrishnan P. Kunjan ◽  
Ajax John ◽  
Tom Jose

Background: Management of intra parenchymal hematoma is a dilemma for neuroscientists, still a life-threatening entity which needs multidisciplinary approach.13% of all strokes constitutes hemorrhagic. Mortality and morbidity of patients depends on the status of initial presentation. Prognosis of the surgeries may vary from person to person and according to the comorbidities. The aim of the study was to determine effectiveness of decompressive craniectomy (DC) with hematoma evacuation in reducing the mortality.Methods: Patients with spontaneous intra parenchymal hematomas were selected and those having herniation syndrome were considered for surgery. Patients were evaluated after 30 days and 6 months and mortality was calculated.Results: 126 patients were selected for surgery, in that 102 patients underwent DC with hematoma evacuation and 24 patients who were not willing for surgery were considered as control group. Mortality of patients at 30 days of surgical group was 19.6% and 58.3% respectively, while 6 months mortality was 31.3% and 70.8% for surgical and control group.Conclusions: Surgical intervention can effectively reduce the mortality in spontaneous intra parenchymal hematomas.


2021 ◽  
Author(s):  
De-Huan Xie ◽  
Yi-Chuan Li ◽  
Sai Ma ◽  
Xin Yang ◽  
Ruo-Ming Lan ◽  
...  

Abstract Purpose: Ultra-high dose rate FLASH irradiation has been shown to cause less normal tissue damage compared with conventional irradiation, also termed “FLASH effect”. However, the underlying mechanism was scarcely known. The purpose of the present study was to determine whether FLASH and conventional irradiation would induce differential inflammatory cytokines expression. Materials and methods: Female FvB mice were randomly assigned to three different groups: non-irradiated control, conventional (CONV) and FLASH groups. Mice were irradiated at 6 to 19 Gy of CONV (0.1 Gy/s) or FLASH (38.5-600 Gy/s) irradiation using an Elekta Synergy linac (6 MeV). Mice were immobilized in prone position in a custom-designed applicator with dosimetry films positioned under the body. Dose were verified by Gafchromic films. Enzyme linked immunosorbent assay (ELISA) were performed in serum samples of the mice at 6, 18 and 31 days after irradiation for four inflammatory cytokines: tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6) and IL-10. Flow cytometry using antibodies for CD3, CD8, CD4 and CD45 in blood were performed pre- and 1-week post irradiation. Results: At D6 (18-19 Gy), both IL-6 and TNF-α were elevated, and IL-10 was reduced in FLASH and CONV group, while IFN-γ was only significantly increased in conventional group, compared with control group. At D18 (10 Gy) and D31 (13-19 Gy), conventional RT significantly elevated levels of IL-6, IFN-γ and TNF-α and reduced IL-10 level compared with FLASH group and control group. Additionally, even low dose conventional irradiation (13 Gy) could induce higher level of pro-inflammatory cytokines and lower level of anti-inflammatory cytokine than high dose (17-19 Gy) FLASH irradiation at D31. Flow cytometry showed that the CD8+/CD45+ ratio in the blood were higher in the conventional than in FLASH. These data indicate that minor inflammatory cytokine levels of serum in FLASH could be result of the absent of immune overactivation induced by conventional irradiation. Conclusions: Ultra-high dose rate electron FLASH caused less inflammatory cytokine levels of serum which might be a result from less CD8+/CD45+ ratio in the blood. Thus, differential cytokines and CD8+ T cell expression between FLASH and conventional irradiation would be a potential mechanism for “FLASH effect”.


2014 ◽  
Vol 34 (4) ◽  
pp. 430-438 ◽  
Author(s):  
J Qian ◽  
L Liu ◽  
L Chen ◽  
X Lu ◽  
C Zhu

Background: Toll-like receptor 9 (TLR9), an important component of the innate immune system, contributes to the pathogenesis of lung injury. However, its role in paraquat (PQ)-induced lung injury has not been studied. Method: Mice were divided into PQ group ( n = 24) and control group ( n = 12). Mice in both groups were killed on either day 7 or day 28 after PQ (40 mg/kg intraperitoneally) or saline administration. TLR9 expression was evaluated through real-time polymerase chain reaction and immunohistochemistry. Concurrently, histopathological examinations of lung tissues were performed. On day 7, the lung weight to body weight ratios (LW/BW), total protein content, and inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) were measured. On day 28, fibrogenic cytokine expressions in lung tissues were measured. The correlations between TLR9 messenger RNA (mRNA) expression and different indicators of lung injury were then evaluated. Results: TLR9 expression was significantly increased over time in lung tissues after PQ poisoning. On day 7, TLR9 expression increased in parallel with LW/BW ratio ( r = 0.403, p < 0.05), BALF protein content ( r = 0.706, p<0.01), and BALF inflammatory cytokine levels (interleukin 6 (IL-6): r = 0.619, IL-1β: r = 0.930, tumor necrosis factor α: r = 0.589, all p < 0.05). On day 28, elevated TLR9 expression was closely correlated with Ashcroft score ( r = 0.726, p < 0.01), mRNA expressions of α-smooth muscle actin, type I collagen and type III collagen ( r = 0.926, 0.957, and 0.924, respectively; all p < 0.01). Conclusions: The TLR9 expression in lung tissue is markedly elevated during PQ-induced acute lung injury and pulmonary fibrosis and positively correlated with the severity of lung injury in mice.


2020 ◽  
Vol 32 (1) ◽  
Author(s):  
Ghada A. Mohamed ◽  
Mohamed Z. Abd-Elrahman ◽  
Rania Bahriz ◽  
Ahmed Albehairy

Abstract Background In adults with diabetic ketoacidosis (DKA), high plasma levels of C-reactive protein (CRP) and inflammatory cytokines such as interleukin-6 (IL-6) were reported to be sensitive markers of infection. However, elevation of both CRP and the pro-inflammatory cytokines which regulate CRP are probable without infection and may act as indicator of systemic inflammatory response (SIR). So, we wanted to determine if increased plasma CRP levels occur in young patients with severe DKA who do not have clinical evidence of infection and to relate observed changes in CRP level to the pro-inflammatory cytokine levels. Results Upon admission of 30 DKA patients with age ranging from 17 to 40 years, we found significant elevation of CRP (P = 0.001) and IL-6 (P = 0.001) in DKA patients than control group. After resolution of DKA, there was significant reduction in CRP and IL-6 compared to before DKA correction (P value = 0.054 and 0.001), respectively. There was a significant negative correlation between CRP after correction of DKA and RBCs (P = 0.042), and serum K (P = 0.021) and between CRP prior to DKA correction and PH (P = 0.025). Conclusions Patients with DKA without infection had increased levels of CRP and inflammatory cytokines. Intensive insulin therapy has a powerful anti-inflammatory effect that, at the time of DKA improvement, can normalize levels of CRP and inflammatory cytokines, and this beneficial effect is greater for IL-6 than CRP.


2019 ◽  
Author(s):  
Bruno Pedraz Petrozzi ◽  
Elena Neumann ◽  
Gebhard Sammer

Abstract 1. AbstractBackground: Depression represents a highly disabling disease. A relationship between augmented cytokine concentrations and depression has been suggested. Fatigue, frequently being part of depressive symptoms and being associated with infectious diseases and autoimmune diseases, could constitute a link between inflammation mechanisms and depression. The aim of this work was to show the pattern of relationships between depression, fatigue, and inflammation. Methods: A case-control study with 27 patients and 33 matched controls was conducted. IL-6, IL-1β, TNF-α, IFN-γ and CRP were assessed in venous blood samples. Fatigue was assessed behaviorally with a sustained attention task (SAT) and subjectively with a questionnaire (FIS-D). Depression scores were assessed using a questionnaire (BDI-FS). Results: IL-6 was higher in the patient group (U test = 304.00; p = 0.045). For the whole sample size, IL-1β concentration differences were found between BDI-FS categories (H (3) = 11.34, p = 0.01). In patients, correlations were found between BDI-FS categories and IL-1β (ρ = 0.409, p = 0.038), psychosocial fatigue and IL-6 (ρ = 0.437, p = 0.029), and somatic fatigue and TNF-α (ρ = 0.390, p = 0.049). However, correlations failed p = 0.05 threshold for controls. Finally, the total number of omitted responses in the SAT and TNF-α were positively correlated in the patient group (ρ = 0.488, p = 0.011) as well as in the control group (ρ = 0.454, p = 0.008). Conclusions: The results suggest the presence of inflammation in both depression and fatigue. However, each correlates with different pro-inflammatory parameters, indicating potential biological heterogeneity.


2017 ◽  
Vol 21 (2) ◽  
pp. 73-82
Author(s):  
E. I. Slobodian ◽  
N. N. Kaladze ◽  
A. L. Govdalyuk

THE AIM:to evaluate diagnostic significance of clinical and laboratory resistance in determining urine cytokines in patients with chronic pyelonephritis (CP).PATIENTS AND METHODS.This prospective study included 110 children with CP aged 6 to 16 years in a state of clinical and laboratory remission. The control group consisted of 20 apparently healthy children. Laboratory tests used to determine EGF, TGF-β1, IGF-1, β2 – MG, IL-4, IL-10, IL-17 and IL-12 by ELISA in the morning urine of patients.RESULTS.Comparison of cytokines values depending on the clinical form of the disease revealed the prevalence of levels of TGF-β1 and IL-17 in the urine of patients with obstructive CP. The highest uTGF-β1 / uCr and uIL-17 / uCr were obtained in patients, which have vesicoureteral reflux in anamnesis. Level uIL-10 / uCr almost 2 times was elevated in children with both clinical forms of CP. In patients with the disease experience up to 6 years, were identified unidirectional changes of urine cytokines – increase in both pro- and anti-inflammatory parameters. As the duration of the microbial-inflammatory processes more than 6 years there was a significant decrease in the levels uIGF-1 / uCr and uEGF-1 / uCr relative to the control group, with no significant changes in the uIL-12 / uCr and uIL-10 / uCr at continuing higher levels uTGF-β1 / uCr, uIL-17 / uCr, uIL-4 / uCr. In patients having one or less exacerbation of CP per year, regardless of the duration of the disease, no pathological changes in cytokine levels have been detected. Most of the studied parameters were dependent on renal function.CONCLUSION.Increased concentration of studied urine cytokines indicates the presence of a latent inflammatory process more than in half of studied patients. 


2020 ◽  
Vol 8 (3) ◽  
pp. 103-112
Author(s):  
Atefeh SADEGHI SHERMEH ◽  
Majid KHOSHMIRSAFA ◽  
Ali-Akbar DELBANDI ◽  
Payam TABARSI ◽  
Esmaeil MORTAZ ◽  
...  

Introduction: Tuberculosis (TB) and especially resistant forms of it have a substantial economic burden on the community health system for diagnosis and treatment each year. Thus, investigation of this field is a priority for the world health organization (WHO). Cytokines play important roles in the relationship between the immune system and tuberculosis. Genetic variations especially single nucleotide polymorphisms (SNPs) impact cytokine levels and function against TB. Material and Methods: In this research SNPs in IFN-γ (+874 T/A) and IL-10 (-592 A/C) genes, and the effects of these SNPs on cytokine levels in a total of 87 tuberculosis patients and 100 healthy controls (HCs) were studied. TB patients divided into two groups: 1) 67 drug-sensitive (DS-TB) and 2) 20 drug-resistant (DR-TB) according to drug sensitivity test using polymerase chain reaction (PCR). For the genotyping of two SNPs, the PCR-based method was used and IFN-γ and IL-10 levels were measured by ELISA in pulmonary tuberculosis (PTB) and control group. Results: In -592A/C SNP, only two genotypes (AA, AC) were observed and both genotypes showed statistically significant differences between DR-TB and HCs (p=0.011). IL-10 serum levels in PTB patients were higher than HCs (p=0.02). The serum levels of IFN-γ were significantly higher in DS-TB patients than that of the other two groups (p<0.001); however, no significant differences were observed for allele and genotype frequencies in IFN-γ +874. Conclusions: Our results suggest that the SNP at -592 position of IL-10 gene may be associated with the susceptibility to DR-TB. However, further investigation is necessary. Keywords: Polymorphism, IFN-γ, IL-10, tuberculosis, drug-resistant tuberculosis


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