oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
P2X7 receptor activation ameliorates CA3 neuronal damage via a tumor necrosis factor-α-mediated pathway in the rat hippocampus following status epilepticus
Ji-Eun Kim, Hea Jin Ryu, Tae-Cheon Kang
Journal of Neuroinflammation , 2011, DOI: 10.1186/1742-2094-8-62
Abstract: SE was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-, 2',3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP), A-438079, or A-740003 prior to SE induction. Thereafter, we performed Fluoro-Jade B staining and immunohistochemical studies for TNF-α and NF-κB subunit phosphorylations.Following SE, P2X7 receptor agonist (BzATP) infusion increased TNF-α immunoreactivity in dentate granule cells as compared with that in saline-infused animals. In addition, TNF-α immunoreactivity was readily apparent in the mossy fibers, while TNF-α immunoreactivity in CA1-3 pyramidal cells was unaltered. However, P2X7 receptor antagonist (OxATP-, A-438079, and A-740003) infusion reduced SE-induced TNF-α expression in dentate granule cells. In the CA3 region, BzATP infusion attenuated SE-induced neuronal damage, accompanied by enhancement of p65-Ser276 and p65-Ser311 NF-κB subunit phosphorylations. In contrast, OxATP-, A-438079, and A-740003 infusions increased SE-induced neuronal death. Soluble TNF p55 receptor (sTNFp55R), and cotreatment with BzATP and sTNFp55R infusion also increased SE-induced neuronal damage in CA3 region. However, OxATP-, sTNFp55R or BzATP+sTNFp55R infusions could not exacerbate SE-induced neuronal damages in the dentate gyrus and the CA1 region, as compared to BzATP infusion.These findings suggest that TNF-α induction by P2X7 receptor activation may ameliorate SE-induced CA3 neuronal damage via enhancing NF-κB p65-Ser276 and p65-Ser311 phosphorylations.Status epilepticus (SE) is a medical emergency with significant mortality [1]. SE has been defined as continuous seizure activity, which causes neuronal cell death [2,3], epileptogenesis [3] and learning impairment [4]. Cytokines are critical mediators of specific inflammatory responses and immune reactions in the brain [5]. Tumor necrosis factor-α (TNF-α) is a 17-kDa protein that is mainly produced by activated macrophag
Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors  [PDF]
Cecilia Cs?lle, Mária Baranyi, Gabriella Zsilla, ágnes Kittel, Flóra G?l?ncsér, Peter Illes, Edit Papp, E. Sylvester Vizi, Beáta Sperlágh
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066547
Abstract: Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7?/?) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7?/? mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7?/? mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7?/? mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7?/? mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7?/? mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7?/? mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7?/? mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus.
Modulating P2X7 Receptor Signaling during Rheumatoid Arthritis: New Therapeutic Approaches for Bisphosphonates  [PDF]
Alberto Baroja-Mazo,Pablo Pelegrín
Journal of Osteoporosis , 2012, DOI: 10.1155/2012/408242
Abstract: P2X7 receptor-mediated purinergic signaling is a well-known mechanism involved in bone remodeling. The P2X7 receptor has been implicated in the pathophysiology of various bone and cartilage diseases, including rheumatoid arthritis (RA), a widespread and complex chronic inflammatory disorder. The P2X7 receptor induces the release into the synovial fluid of the proinflammatory factors (e.g., interleukin-1β, prostaglandins, and proteases) responsible for the clinical symptoms of RA. Thus, the P2X7 receptor is emerging as a novel anti-inflammatory therapeutic target, and various selective P2X7 receptor antagonists are under clinical trials. Extracellular ATP signaling acting through the P2X7 receptor is a complex and dynamic scenario, which varies over the course of inflammation. This signaling is partially modulated by the activity of ectonucleotidases, which degrade extracellular ATP to generate other active molecules such as adenosine or pyrophosphates. Recent evidence suggests differential extracellular metabolism of ATP during the resolution of inflammation to generate pyrophosphates. Extracellular pyrophosphate dampens proinflammatory signaling by promoting alternative macrophage activation. Our paper shows that bisphosphonates are metabolically stable pyrophosphate analogues that are able to mimic the anti-inflammatory function of pyrophosphates. Bisphosphonates are arising per se as promising anti-inflammatory drugs to treat RA, and this therapy could be improved when administrated in combination with P2X7 receptor antagonists. 1. Introduction Rheumatoid arthritis (RA) is a widespread chronic systemic inflammatory disorder that affects approximately 1% of the worldwide population. The female-to-male ratio of the disease is 3?:?1, and although it can occur at any age, it is more common between ages 40 and 70 years [1]. In this context, pharmaceutical companies are interested in developing new anti-inflammatory treatments for the disease, including the use of P2X7 receptor antagonists or bisphosphonates [2, 3]. This paper will focus on the role of P2X7 receptors in the pathophysiology of RA and the possible therapeutic connection of bisphosphonates with P2X7 receptor signaling. 2. P2X7 Receptor in Bone and Cartilage Bone is a specialized connective tissue composed of mineralized extracellular matrix and distinct cell populations including osteoblasts, osteocytes, and osteoclasts. Under physiological conditions, bone is subjected to a continuous balance between resorption and formation. However, disturbances of this balance can lead to various diseases
Modulating P2X7 Receptor Signaling during Rheumatoid Arthritis: New Therapeutic Approaches for Bisphosphonates  [PDF]
Alberto Baroja-Mazo,Pablo Pelegrín
Journal of Osteoporosis , 2012, DOI: 10.1155/2012/408242
Abstract: P2X7 receptor-mediated purinergic signaling is a well-known mechanism involved in bone remodeling. The P2X7 receptor has been implicated in the pathophysiology of various bone and cartilage diseases, including rheumatoid arthritis (RA), a widespread and complex chronic inflammatory disorder. The P2X7 receptor induces the release into the synovial fluid of the proinflammatory factors (e.g., interleukin-1β, prostaglandins, and proteases) responsible for the clinical symptoms of RA. Thus, the P2X7 receptor is emerging as a novel anti-inflammatory therapeutic target, and various selective P2X7 receptor antagonists are under clinical trials. Extracellular ATP signaling acting through the P2X7 receptor is a complex and dynamic scenario, which varies over the course of inflammation. This signaling is partially modulated by the activity of ectonucleotidases, which degrade extracellular ATP to generate other active molecules such as adenosine or pyrophosphates. Recent evidence suggests differential extracellular metabolism of ATP during the resolution of inflammation to generate pyrophosphates. Extracellular pyrophosphate dampens proinflammatory signaling by promoting alternative macrophage activation. Our paper shows that bisphosphonates are metabolically stable pyrophosphate analogues that are able to mimic the anti-inflammatory function of pyrophosphates. Bisphosphonates are arising per se as promising anti-inflammatory drugs to treat RA, and this therapy could be improved when administrated in combination with P2X7 receptor antagonists.
Postconditioning ameliorates lipid peroxidation in liver ischemia-reperfusion injury in rats
Teixeira, Antonio Roberto Franchi;Molan, Nilza T.;Kubrusly, Márcia Saldanha;Bellodi-Privato, Marta;Coelho, Ana Maria;Leite, Kátia R.;Machado, Marcel Autran Cesar;Bacchella, Telésforo;Machado, Marcel Cerqueira César;
Acta Cirurgica Brasileira , 2009, DOI: 10.1590/S0102-86502009000100011
Abstract: purpose: liver ischemia-reperfusion injury is a phenomenon presents in events like liver resections and transplantation. the restoration of blood flow may leads to local and systemic injury. several techniques have been developed in order to avoid or ameliorate ischemia-reperfusion injury in clinical situations. the application of a sttuter reperfusion after the ischemic event (postconditioning) could alters the hydrodynamics and stimulates endogenous mechanisms that attenuate the reperfusion injury. the present study was designed to evaluate the potential protective effect of postconditioning in a model of ischemia-reperfusion in rats. methods: hepatic anterior pedicle of median and left anterolateral segments were exposed and clamped for 1 hour. two hours later, clamp was released in two different ways: control group (n=7): clamp was release straightforward; postconditioning group (n=7): clamp was released intermittently. lipid peroxidation (malondialdehyde) and expression of the glutathione-s-transferase-α-3 gene were studied. results: lipid peroxidation was significantly decreased in ischemic and non-ischemic liver by postconditioning. gst- α3 gene was overexpressed in postconditioned group, but not significantly. conclusion: postconditioning induced hepatoprotection by reducing lipid peroxidation in the ischemic and non-ischemic liver.
The role of calcium in modulating the reactivity of the smooth muscle cells during ischemia/reperfusion. Part 2  [PDF]
Katarzyna Szadujkis-Szadurska,Rafa? Szadujkis-Szadurski,Leszek Szadujkis-Szadurski,Grzegorz Grze?k
Post?py Higieny i Medycyny Do?wiadczalnej , 2010,
Abstract: Background:Damage of transplanted organs during reperfusion is still a problem that prompts the search for new drugs able to diminish the risk of graft rejection. The aim of this study was to examine the influence of antioxidant system on the contraction of arteries induced by angiotensin II during ischemia/reperfusion and to determine the role of intracellular and extracellular calcium ions under these conditions.Material/Methods:The experiments were performed on male Wistar rats’ tail arteries. The effects of angiotensin II on vascular tone were examined after ischemia/reperfusion in the presence of catalase or aminotriazole. To determine the role of intracellular and extracellular Ca[sup]2 [/sup], the experiments were performed in Ca[sup]2 [/sup]-free PSS and PSS.Results:Angiotensin II increased perfusion pressure in both Ca[sup]2 [/sup]-free PSS and PSS. After ischemia, the reactions induced by angiotensin II were lower, while after reperfusion they were higher. In the presence of catalase the effects induced by angiotensin II were lower and in the presence of aminotriazole higher.Conclusions:Ischemia inhibits and reperfusion augments the perfusion pressure induced by angiotensin II. The results confirm the vasoprotective effect of catalase and the destructive influence of aminotriazole in modulating the reactions of vascular smooth muscle cells to ANG II after ischemia/reperfusion. These results suggest that the antioxidant system plays a role in modulating the reactions induced by angiotensin II after ischemia/reperfusion and that reperfusion disturbs the balance between antioxidants and the production of reactive oxygen species.
Antiapoptotic Effect of Simvastatin Ameliorates Myocardial Ischemia/Reperfusion Injury  [PDF]
Najah R. Hadi,Fadhil Al-amran,Maitham Yousif,Suhaad T. Zamil
ISRN Pharmacology , 2013, DOI: 10.1155/2013/815094
Abstract: Background. Myocardial ischemial reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty, and coronary bypass surgery. Injury of myocardium due to ischemial reperfusion includes cardiac contractile dysfunction, arrhythmias, and irreversible myocytes damage. These changes are considered to be the consequence of imbalance between the formation of oxidants and the availability of endogenous antioxidants in the heart. Objective. This study was undertaken to investigate the potential role of Simvastatin in the amelioration of myocardial I/R injury induced by ligation of coronary artery in a rat model. Materials and Methods. Adult male Swiss Albino rats were randomized into 4 equal groups. Group (1): sham group: rats underwent the same anesthetic and surgical procedures as those in the control group except ligation of LAD coronary artery, group (2): control group: rats were subjected to regional ischemia for 25?min and reperfusion for 2 hours by ligation of LAD coronary artery, group (3): control vehicle group: rats received vehicle of Simvastatin (normal saline) via IP injection and were subjected to regional ischemia for 25?min and reperfusion for 2 hours by ligation of LAD coronary artery, group (4): Simvastatin treated group: rats were pretreated with Simvastatin 1?mg/kg i.p. 1?hr before ligation of LAD coronary artery. At the end of experiment (2?hr of reperfusion), blood samples were collected from the heart for the measurement of plasma level of cardiac troponin I (cTnI). After that the heart was harvested and divided into 3 parts; one part was used for measurement of apoptosis, another part was homogenized for the measurement of tissue tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α, and the last part for histopathology study. Results. Compared with the sham group, levels of myocardial TNF-α and IL-1β, IL-6, MCP-1, and MIP-1α and plasma cTnI were increased ( ). Histologically, all rats in control group showed significant ( ) cardiac injury. Furthermore, all rats in control group showed significant ( ) apoptosis. Simvastatin significantly counteracted the increase in myocardium level of TNF-α, IL-1B, IL-6, MCP-1 and MIP-1α, plasma cTnI, and apoptosis ( ). Histological analysis revealed that Simvastatin markedly reduced ( ) the severity of heart injury in the rats that underwent LAD ligation procedure. Conclusions. The results of the present study reveal that Simvastatin may ameliorate myocardial I/R injury in rats
The Role of Cannabinoids in Modulating Emotional and Non-Emotional Memory Processes in the Hippocampus  [PDF]
Irit Akirav
Frontiers in Behavioral Neuroscience , 2011, DOI: 10.3389/fnbeh.2011.00034
Abstract: Cannabinoid agonists generally have a disruptive effect on memory, learning, and operant behavior that is considered to be hippocampus-dependent. Nevertheless, under certain conditions, cannabinoid receptor activation may facilitate neuronal learning processes. For example, CB1 receptors are essential for the extinction of conditioned fear associations, indicating an important role for this receptor in neuronal emotional learning and memory. This review examines the diverse effects of cannabinoids on hippocampal memory and plasticity. It shows how the effects of cannabinoid receptor activation may vary depending on the route of administration, the nature of the task (aversive or not), and whether it involves emotional memory formation (e.g., conditioned fear and extinction learning) or non-emotional memory formation (e.g., spatial learning). It also examines the memory stage under investigation (acquisition, consolidation, retrieval, extinction), and the brain areas involved. Differences between the effects of exogenous and endogenous agonists are also discussed. The apparently biphasic effects of cannabinoids on anxiety is noted as this implies that the effects of cannabinoid receptor agonists on hippocampal learning and memory may be attributable to a general modulation of anxiety or stress levels and not to memory per se. The review concludes that cannabinoids have diverse effects on hippocampal memory and plasticity that cannot be categorized simply into an impairing or an enhancing effect. A better understanding of the involvement of cannabinoids in memory processes will help determine whether the benefits of the clinical use of cannabinoids outweigh the risks of possible memory impairments.
Impaired Interleukin-1β and c-Fos Expression in the Hippocampus Is Associated with a Spatial Memory Deficit in P2X7 Receptor-Deficient Mice
Virginie F. Labrousse,Laurence Costes,Agnès Aubert,Muriel Darnaudéry,Guillaume Ferreira,Thierry Amédée,Sophie Layé
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0006006
Abstract: Recent evidence suggests that interleukin-1β (IL-1β), which was originally identified as a proinflammatory cytokine, is also required in the brain for memory processes. We have previously shown that IL-1β synthesis in the hippocampus is dependent on P2X7 receptor (P2X7R), which is an ionotropic receptor of ATP. To substantiate the role of P2X7R in both brain IL-1β expression and memory processes, we examined the induction of IL-1β mRNA expression in the hippocampus of wild-type (WT) and homozygous P2X7 receptor knockout mice (P2X7R?/?) following a spatial memory task. The spatial recognition task induced both IL-1β mRNA expression and c-Fos protein activation in the hippocampus of WT but not of P2X7R?/? mice. Remarkably, P2X7R?/? mice displayed spatial memory impairment in a hippocampal-dependant task, while their performances in an object recognition task were unaltered. Taken together, our results show that P2X7R plays a critical role in spatial memory processes and the associated hippocampal IL-1β mRNA synthesis and c-Fos activation.
Erythropoietin ameliorates early ischemia-reperfusion injury following the Pringle maneuver  [cached]
Masato Kato, Tokihiko Sawada, Junji Kita, Mitsugi Shimoda, Keiichi Kubota
World Journal of Gastroenterology , 2010,
Abstract: AIM: To investigate the protective effect of erythropoietin (Epo) against ischemia-reperfusion injury (IR/I) following the Pringle maneuver (PM), in comparison with conventional steroid administration in a prospective randomized trial.METHODS: Patients were randomized by age, sex, diagnosis, and surgical method, and assigned to three groups: (1) A steroid group (STRD, n = 9) who received 100 mg of hydrocortisone before PM, and on postoperative days 1, 2 and 3, followed by tapering until postoperative day 7; (2) An EPO1 group (n = 10) who received 30 000 U of Epo before the PM and at the end of surgery; and (3) An EPO2 group (n = 8) who received 60 000 U of Epo before the PM. Hemoglobin (Hb), hematocrit (Ht), aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), lactate, interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α were measured before and just after (Day 0) surgery, and on postoperative days 1, 3, 7 and 14.RESULTS: There were no increases in Hb and Ht in the EPO1 and EPO2 groups. AST was significantly lower in EPO1 than in STRD on Day 0 (P = 0.041), and lower in EPO1 than in STRD and EPO2 on Day 1 (P = 0.018). ALT was significantly lower in EPO1 than in STRD and EPO2 on Day 0 (P = 0.020) and Day 1 (P = 0.004). There were no significant inter-group differences in the levels of LDH and lactate. IL-6 was significantly lower in EPO1 than in STRD and EPO2 on Day 0 (P = 0.0036) and Day 1 (P = 0.0451). TNF-α was significantly lower in EPO1 than in STRD and EPO2 on Day 0 (P = 0.0006) and Day 1 (P < 0.0001). Furthermore, hospitalization was significantly shorter in EPO1 and EPO2 than in STRD.CONCLUSION: Epo has greater potential than steroids to ameliorate IR/I after the PM. Epo at a dose of 30 000 U, administered before PM and just after surgery, yields better results.
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.