Experimental Models of Streptococcal Arthritis: Pathogenetic Role of Streptococcal Products and Prostaglandins and Their Modification by Anti-Inflammatory Agents

Author(s):  
I. Ginsburg ◽  
U. Zor ◽  
Y. Floman
2021 ◽  
Vol 12 ◽  
Author(s):  
Gary P. Brennan ◽  
Megan M. Garcia-Curran ◽  
Katelin P. Patterson ◽  
Renhao Luo ◽  
Tallie Z. Baram

Background and Rationale: Bi-directional neuronal-glial communication is a critical mediator of normal brain function and is disrupted in the epileptic brain. The potential role of aberrant microglia and astrocyte function during epileptogenesis is important because the mediators involved provide tangible targets for intervention and prevention of epilepsy. Glial activation is intrinsically involved in the generation of childhood febrile seizures (FS), and prolonged FS (febrile status epilepticus, FSE) antecede a proportion of adult temporal lobe epilepsy (TLE). Because TLE is often refractory to treatment and accompanied by significant memory and emotional difficulties, we probed the role of disruptions of glial-neuronal networks in the epileptogenesis that follows experimental FSE (eFSE).Methods: We performed a multi-pronged examination of neuronal-glia communication and the resulting activation of molecular signaling cascades in these cell types following eFSE in immature mice and rats. Specifically, we examined pathways involving cytokines, microRNAs, high mobility group B-1 (HMGB1) and the prostaglandin E2 signaling. We aimed to block epileptogenesis using network-specific interventions as well as via a global anti-inflammatory approach using dexamethasone.Results: (A) eFSE elicited a strong inflammatory response with rapid and sustained upregulation of pro-inflammatory cytokines. (B) Within minutes of the end of the eFSE, HMGB1 translocated from neuronal nuclei to dendrites, en route to the extracellular space and glial Toll-like receptors. Administration of an HMGB1 blocker to eFSE rat pups did not decrease expression of downstream inflammatory cascades and led to unacceptable side effects. (C) Prolonged seizure-like activity caused overall microRNA-124 (miR-124) levels to plunge in hippocampus and release of this microRNA from neurons via extra-cellular vesicles. (D) Within hours of eFSE, structural astrocyte and microglia activation was associated not only with cytokine production, but also with activation of the PGE2 cascade. However, administration of TG6-10-1, a blocker of the PGE2 receptor EP2 had little effect on spike-series provoked by eFSE. (E) In contrast to the failure of selective interventions, a 3-day treatment of eFSE–experiencing rat pups with the broad anti-inflammatory drug dexamethasone attenuated eFSE-provoked pro-epileptogenic EEG changes.Conclusions: eFSE, a provoker of TLE-like epilepsy in rodents leads to multiple and rapid disruptions of interconnected glial-neuronal networks, with a likely important role in epileptogenesis. The intricate, cell-specific and homeostatic interplays among these networks constitute a serious challenge to effective selective interventions that aim to prevent epilepsy. In contrast, a broad suppression of glial-neuronal dysfunction holds promise for mitigating FSE-induced hyperexcitability and epileptogenesis in experimental models and in humans.


2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
J. Stefanska ◽  
R. Pawliczak

Apocynin is a naturally occurring methoxy-substituted catechol, experimentally used as an inhibitor of NADPH-oxidase. It can decrease the production of superoxide (O2−) from activated neutrophils and macrophages while the ability of phagocytosis remains unaffected. The anti-inflammatory activity of apocynin has been demonstrated in a variety of cell and animal models of inflammation. Apocynin, after metabolic conversion, inhibits the assembly of NADPH-oxidase that is responsible for reactive oxygen species (ROS) production. It is, therefore, extensively used to reveal the role of this enzyme in cell and experimental models. Although some of the ROS serve as signaling molecules in the cells, excessive production is damaging and has been implicated to play an important role in the progression of many disease processes. This is why in many studies apocynin presents a promising potential treatment for some disorders; however, its utility with inflammatory diseases remains to be determined. Since its mode of action is not well defined, we tried to get a more precise insight into the mechanisms by which apocynin exerts its activity. Considering the anti-inflammatory activities of apocynin, we may conclude that this compound definitely deserves further study.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Edgar Ramos-Martinez ◽  
Ivan Ramos-Martínez ◽  
Gladys Molina-Salinas ◽  
Wendy A. Zepeda-Ruiz ◽  
Marco Cerbon

Abstract Prolactin has been shown to favor both the activation and suppression of the microglia and astrocytes, as well as the release of inflammatory and anti-inflammatory cytokines. Prolactin has also been associated with neuronal damage in diseases such as multiple sclerosis, epilepsy, and in experimental models of these diseases. However, studies show that prolactin has neuroprotective effects in conditions of neuronal damage and inflammation and may be used as neuroprotector factor. In this review, we first discuss general information about prolactin, then we summarize recent findings of prolactin function in inflammatory and anti-inflammatory processes and factors involved in the possible dual role of prolactin are described. Finally, we review the function of prolactin specifically in the central nervous system and how it promotes a neuroprotective effect, or that of neuronal damage, particularly in experimental autoimmune encephalomyelitis and during excitotoxicity. The overall studies indicated that prolactin may be a promising molecule for the treatment of some neurological diseases.


Author(s):  
Amos O. Abolaji ◽  
Marvis U. Omozokpia ◽  
Olajide J. Oluwamuyide ◽  
Temidayo E. Akintola ◽  
Ebenezer O. Farombi

AbstractBackgroundThe ovotoxicity of 4-vinylcyclohexene diepoxide (VCD) has been established in several experimental models. Hesperidin (HSD) is a bi-flavonoid found in citrus fruits and has been reported to be a potent antioxidant and anti-inflammatory agent. Here, we have evaluated the rescue role of hesperidin on VCD-induced toxicity in the brain, ovary, and uterus of rats.MethodsSix groups of rats containing ten rats in each group were orally given corn oil (control), hesperidin (100 mg/kg), hesperidin (200 mg/kg), VCD (250 mg/kg), VCD [(250 mg/kg)+hesperidin (100 mg/kg)] and VCD [(250 mg/kg)+hesperidin (200 mg/kg)] once a day for 30 days, respectively. Thereafter, we determined the selected biomarkers of oxidative damage, inflammation, endocrine balance, and histology of the reproductive organs.ResultsThe data showed that hesperidin rescued VCD-induced increase in oxidative stress (hydrogen peroxide and malondialdehyde) and inflammatory (nitric oxide) biomarkers. In addition, hesperidin restored the reduction in antioxidant enzymes (catalase, glutathione S-transferase, glutathione peroxidase) activities and glutathione level in the brain, ovary, and uterus of rats (p<0.05). Lastly, hesperidin preserved the histological structure of the ovary and uterus of rats exposed to VCD.ConclusionsOverall, the rescue role of hesperidin on VCD-induced toxicity in the brain and reproductive organs of female rats may be due to its antioxidative and anti-inflammatory properties.


Folia Medica ◽  
2014 ◽  
Vol 56 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Ilia D. Kostadinov ◽  
Delian P. Delev ◽  
Marianna A. Murdjeva ◽  
Ivanka I. Kostadinova

ABSTRACT INTRODUCTION: Fluoxetine is an antidepressant that has anti-inflammatory and antihyperalgesic effects in experimental models of pain and inflammation. The AIM of the present study was to determine the role of 5-HT2 receptors in the mechanism of anti-inflammatory and antihyperalgesic action of fluoxetine after single and repeated administration of the drug. MATERIALS AND METHODS: 40 male Wistar rats were randomly divided in five groups (n = 8) treated for 14 days with saline (control), diclofenac (positive control), fluoxetine, cyproheptadine (5-HT2 antagonist), and fluoxetine + cyproheptadine, respectively. We used the experimental model of inflammation induced by intraplantar injection of carrageenan and nociceptive test with mechanical pressure on the inflamed hind paw. RESULTS: Single and repeated administration of fluoxetine showed that it had significant anti-inflammatory and antihyperalgesic effects when compared with the control (p < 0.05). Cyproheptadine did not change significantly the anti-inflammatory effect of fluoxetine in the first 4 hours, after a single administration. At 24 hours the combination did not differ statistically when compared with the control. Cyproheptadin did not change significantly the anti-inflammatory effect of fluoxetine after repeated administration. After prolonged treatment the group that received fluoxetine + cyproheptadine showed a statistically significant increase in paw pressure to withdraw the hind paw compared with that treated with fluoxetine alone (p < 0.05). CONCLUSIONS: Fluoxetine has anti-inflammatory and antihyperalgesic effects in the carrageenan model of inflammation. 5-HT2 receptor mediated its anti-inflammatory effect in single dose treated animals. Spinal 5-HT2 receptors are involved in the antihyperalgesic effect of fluoxetine after repeated administration


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Dimitra Kelepouri ◽  
Athanasios Mavropoulos ◽  
Dimitrios P. Bogdanos ◽  
Lazaros I. Sakkas

Flavonoids have been considered powerful anti-inflammatory agents, and their exact immunomodulatory action as therapeutic agents in autoimmune diseases has started to emerge. Their role in the manipulation of immunoregulation is less understood. Several studies attempted to investigate the role of various flavonoids mainly in experimental models of autoimmune diseases, especially in the context of their potential effect on the increase of regulatory T cells (Tregs) and their ability to stimulate an overexpression of anti-inflammatory cytokines, in particular that of IL-10. The emergence of IL-17, a cytokine largely produced by Th17 cells, as a powerful proinflammatory stimulus which attenuates the induction of Tregs has prompted a series of studies investigating the role of flavonoids on Th17 cells in experimental models as well as human autoimmune diseases. This review thoroughly discusses accumulated data on the role of flavonoids on Th17 in rheumatoid arthritis and experimental autoimmune arthritis.


2020 ◽  
Vol 51 (2) ◽  
pp. 705-711
Author(s):  
N. Z. Yahya

To evaluate the role of anti-inflammatory and analgesicof Iraqi pumpkin seed oil. The oil seed (25-100 mg / kg) were investigated using various experimental models for analgesic and anti-inflammatory benefit. Acetic acid and thermal induced models of pain were used to examine the anti-nociceptive property. Though models of oedema induced by carragenin were used to evaluate anti-inflammation. Results were reported from these studies that the extract prepared from Iraqi pumpkin seeds possess potential anti-inflammatory and analgesic activity when  compared with standard drug Diclofenac. Even though all the concentrations showed varying degree of inflammatory and analgesic activity, 100mg/kg bw showed better anti inflammatory and analgesic activity


2017 ◽  
Vol 48 (S 01) ◽  
pp. S1-S45
Author(s):  
F. Brackmann ◽  
R. Coras ◽  
K. Rössler ◽  
O. Rompel ◽  
R. Trollmann
Keyword(s):  

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