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Different Animal Models (different + animal_models)
Selected AbstractsEvidence for a Role of the Parafascicular Nucleus of the Thalamus in the Control of Epileptic Seizures by the Superior ColliculusEPILEPSIA, Issue 1 2005Karine Nail-Boucherie Summary:,Purpose: The aim of this study was to investigate whether the nucleus parafascicularis (Pf) of the thalamus could be a relay of the control of epileptic seizures by the superior colliculus (SC). The Pf is one of the main ascending projections of the SC, the disinhibition of which has been shown to suppress seizures in different animal models and has been proposed as the main relay of the nigral control of epilepsy. Methods: Rats with genetic absence seizures (generalized absence epilepsy rat from Strasbourg or GAERS) were used in this study. The effect of bilateral microinjection of picrotoxin, a ,-aminobutyric acid (GABA) antagonist, in the SC on the glutamate and GABA extracellular concentration within the Pf was first investigated by using microdialysis. In a second experiment, the effect of direct activation of Pf neurons on the occurrence of absence seizures was examined with microinjection of low doses of kainate, a glutamate agonist. Results: Bilateral injection of picrotoxin (33 pmol/side) in the SC suppressed spike-and-wave discharges for 20 min. This treatment resulted in an increase of glutamate but not GABA levels in the Pf during the same time course. Bilateral injection of kainate (35 pmol/side) into the Pf significantly suppressed spike-and-wave discharges for 20 min, whereas such injections were without effects when at least one site was located outside the Pf. Conclusions: These data suggest that glutamatergic projections to the Pf could be involved in the control of seizures by the SC. Disinhibition of these neurons could lead to seizure suppression and may be involved in the nigral control of epilepsy. [source] The Anticonvulsant SGB-017 (ADCI) Blocks Voltage-Gated Sodium Channels in Rat and Human Neurons: Comparison with CarbamazepineEPILEPSIA, Issue 3 2000Lucy Sun Summary: Purpose: SGB-017 (ADCI) is a novel anticonvul-sant that blocks both voltage-activated sodium channels and N -methyl- d -aspartate (NMDA)-receptor-gated channels. Results by Rogawski et al. suggested that SGB-017 produces its anticonvulsant action primarily by inhibition of NMDA-receptor channels. However, SGB-017 is effective in several animal models of epilepsy that are unresponsive to NMDA antagonists. These results indicate that block of NMDA-receptor channels is not the only mechanism contributing to its anticonvulsant activity. Thus the effects of SGB-017 on neu-ronal sodium channels were investigated. Methods: Whole cell voltage-clamp techniques were used to record sodium currents in freshly dissociated rat superior cervical ganglion (SCG) and hippocampal neurons and cultured human NT2 neurons. The effects of SGB-017 on the amplitude of sodium currents, elicited by a depolarizing pulse to 0 mV from different holding potentials, were measured and compared with those of carbamazepine (CBZ). Results: SGB-017 inhibited sodium currents in rat SCG and hippocampal neurons with a similar potency to CBZ. Like CBZ, the inhibition of sodium channels by SGB-017 was voltage dependent. Its median inhibitory concentration (IC50) for inhibition of sodium channels at depolarized holding potentials is similar to that for its inhibition of NMDA receptor channels. In human hNT2 neurons, SGB-017 was more potent than CBZ at inhibiting sodium currents. Conclusions: SGB-017 produces its anticonvulsant activity by blocking both sodium- and NMDA-receptor channels in a voltage- and use-dependent manner. The combination of these two mechanisms of action makes SGB-017 an effective AED in several different animal models of epilepsy. [source] Effects of masticatory muscle function on craniofacial morphology in growing ferrets (Mustela putorius furo)EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 6 2003Tailun He Studying the effects of masticatory muscle function on craniofacial morphology in animal models with different masticatory systems is important for further understanding of related issues in humans. Forty 5-wk-old male ferrets were equally divided into two groups. One group was fed a diet of hard pellets (HDG) and the other group was fed the same diet but softened with water (SDG). Lateral and dorsoventral cephalograms were taken on each group after 6 months. Cephalometric measurements were performed by digital procedures. For SDG ferrets, the hard palate plane was more distant from the cranial base plane, and canines were more proclined compared with HDG ferrets. The SDG ferrets were also found to have smaller interfrontal and interparietal widths, and a slenderer zygomatic arch than the HDG ferrets. In the mandible, the coronoid process was generally shorter and narrower for the SDG ferrets. The effects of the altered masticatory muscle function on craniofacial morphology in growing ferrets seemed to differ from those previously reported in other animal models studied under similar experimental conditions. Such differences in the effects are presumably related to the differences in the mode of mastication, craniofacial anatomy and growth pattern in different animal models. [source] Effect of 6-Month Whole Body Vibration Training on Hip Density, Muscle Strength, and Postural Control in Postmenopausal Women: A Randomized Controlled Pilot Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2004Sabine MP Verschueren Abstract High-frequency mechanical strain seems to stimulate bone strength in animals. In this randomized controlled trial, hip BMD was measured in postmenopausal women after a 24-week whole body vibration (WBV) training program. Vibration training significantly increased BMD of the hip. These findings suggest that WBV training might be useful in the prevention of osteoporosis. Introduction: High-frequency mechanical strain has been shown to stimulate bone strength in different animal models. However, the effects of vibration exercise on the human skeleton have rarely been studied. Particularly in postmenopausal women,who are most at risk of developing osteoporosis,randomized controlled data on the safety and efficacy of vibration loading are lacking. The aim of this randomized controlled trial was to assess the musculoskeletal effects of high-frequency loading by means of whole body vibration (WBV) in postmenopausal women. Materials and Methods: Seventy volunteers (age, 58,74 years) were randomly assigned to a whole body vibration training group (WBV, n = 25), a resistance training group (RES, n = 22), or a control group (CON, n = 23). The WBV group and the RES group trained three times weekly for 24 weeks. The WBV group performed static and dynamic knee-extensor exercises on a vibration platform (35,40 Hz, 2.28,5.09g), which mechanically loaded the bone and evoked reflexive muscle contractions. The RES group trained knee extensors by dynamic leg press and leg extension exercises, increasing from low (20 RM) to high (8 RM) resistance. The CON group did not participate in any training. Hip bone density was measured using DXA at baseline and after the 6-month intervention. Isometric and dynamic strength were measured by means of a motor-driven dynamometer. Data were analyzed by means of repeated measures ANOVA. Results: No vibration-related side effects were observed. Vibration training improved isometric and dynamic muscle strength (+15% and + 16%, respectively; p < 0.01) and also significantly increased BMD of the hip (+0.93%, p < 0.05). No changes in hip BMD were observed in women participating in resistance training or age-matched controls (,0.60% and ,0.62%, respectively; not significant). Serum markers of bone turnover did not change in any of the groups. Conclusion: These findings suggest that WBV training may be a feasible and effective way to modify well-recognized risk factors for falls and fractures in older women and support the need for further human studies. [source] Endotoxin translocation in two models of experimental acute pancreatitisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2003C. Vasilescu Abstract To test the hypothesis that endotoxin is absorbed from the gut into the circulation in rats with experimental acute pancreatitis we studied two different animal models. In the first model necrotizing pancreatitis was induced by the ligation of the disatl bilio-pancreatic duct while in the second, experimental oedematous acute pancreatitis was induced by subcutaneous injections of caerulein. In both experiments, in the colon of rats with acute pancreatitis endotoxin from Salmonella abortus equi was injected. Endotoxin was detected by immunohistochemistry in peripheral organs with specific antibodies. The endotoxin was found only in rats with both acute pancreatitis and endotoxin injected into the colon and not in the control groups. The distribution of endotoxin in liver at 3 and 5 days was predominantly at hepatocytes level around terminal hepatic venules, while in lung a scattered diffuse pattern at the level of alveolar macrophages was identified. A positive staining was observed after 12 hours in the liver, lung, colon and mesenteric lymph nodes of rats with both caerulein pancreatitis and endotoxin injected into the colon. We conclude that the experimental acute pancreatitis leads to early endotoxin translocation from the gut lumen in the intestinal wall and consequent access of gut-derived endotoxin to the mesenteric lymph nodes, liver and lung. [source] The green tea compound, (,)-epigallocatechin-3-gallate downregulates N-cadherin and suppresses migration of bladder carcinoma cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2007Kimberly M. Rieger-Christ Abstract Green tea has been reported as potential dietary protection against numerous cancers and has been shown to have activity in bladder tumor inhibition in different animal models. The goal of this study was to examine the effects of (,)-epigallocatechin gallate (EGCG,the major phytochemical in green tea) on growth inhibition and behavior of human bladder carcinoma cells and to identify the altered signaling pathway(s) underlying the response to EGCG exposure. EGCG inhibited the in vitro growth of invasive bladder carcinoma cells with an IC50 range of 70,87 µM. At a concentration of 20 µM, EGCG decreased the migratory potential of bladder carcinoma cells with concomitant activation of p42/44 MAPK and STAT3 and inactivation of Akt. Using biochemical inhibitors of MAPK/ERK, and siRNA to knockdown STAT3 and Akt, inhibition of migration was recorded associated with Akt but not MAPK/ERK or STAT3 signaling in bladder cells. In addition, EGCG downregulated N-cadherin in a dose-dependent manner where reduction in N-cadherin expression paralleled declining migratory potential. Continuous feeding of EGCG to mice prior to and during the establishment of bladder carcinoma xenografts in vivo revealed >50% reduction in mean final tumor volume (P,,,0.05) with no detectable toxicity. EGCG inhibited bladder carcinoma cell growth and suppressed the in vitro migration capacity of cells via downregulation of N-cadherin and inactivation of Akt signaling. Continuous administration of EGCG to mice revealed significant inhibition of tumor growth in vivo indicating a possible preventative role for green tea in bladder cancer. J. Cell. Biochem. 102: 377,388, 2007. © 2007 Wiley-Liss, Inc. [source] Therapeutic potential of melatonin in traumatic central nervous system injuryJOURNAL OF PINEAL RESEARCH, Issue 2 2009Supriti Samantaray Abstract:, A vast literature extolling the benefits of melatonin has accumulated during the past four decades. Melatonin was previously considered of importance to seasonal reproduction and circadian rhythmicity. Currently, it appears to be a versatile anti-oxidative and anti-nitrosative agent, a molecule with immunomodulatory actions and profound oncostatic activity, and also to play a role as a potent neuroprotectant. Nowadays, melatonin is sold as a dietary supplement with differential availability as an over-the-counter aid in different countries. There is a widespread agreement that melatonin is nontoxic and safe considering its frequent, long-term usage by humans at both physiological and pharmacological doses with no reported side effects. Endeavors toward a designated drug status for melatonin may be enormously rewarding in clinics for treatment of several forms of neurotrauma where effective pharmacological intervention has not yet been attained. This mini review consolidates the data regarding the efficacy of melatonin as an unique neuroprotective agent in traumatic central nervous system (CNS) injuries. Well-documented actions of melatonin in combating traumatic CNS damage are compiled from various clinical and experimental studies. Research on traumatic brain injury and ischemia/reperfusion are briefly outlined here as they have been recently reviewed elsewhere, whereas the studies on different animal models of the experimental spinal cord injury have been extensively covered in this mini review for the first time. [source] Usefulness of mouse models to study the pathogenesis of Sjögren's syndromeORAL DISEASES, Issue 4 2007MS Soyfoo Sjögren's syndrome (SS) is an autoimmune disorder characterized by ocular and oral dryness as well as systemic manifestations. The immunopathogenesis of SS is complex with different intricate factors. Because of the delay in the appearance of symptoms and due to ethical issues it is very difficult to study the wide array of factors intervening in the pathogenesis of SS in human patients. To circumvent this problem, different animal models have been elaborated for studying the different subsets of the aspects of the physiopathology of this disease. In this review, we focus on the mouse models that have been established to deepen our insight into the immunopathogenesis of SS. [source] Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease,ANNALS OF NEUROLOGY, Issue 6 2009Fabienne Brilot PhD Objective Myelin oligodendrocyte glycoprotein (MOG) is a candidate target antigen in demyelinating diseases of the central nervous system (CNS). Although MOG is encephalitogenic in different animal models, the relevance of this antigen in human autoimmune diseases of the CNS is still controversial. Methods We investigated the occurrence and biological activity of antibodies to native MOG (nMOG) in 47 children during a first episode of CNS demyelination (acute disseminated encephalomyelitis [ADEM], n = 19 and clinical isolated syndrome [CIS], n = 28) by a cell-based bioassay. Results High serum immunoglobulin G (IgG) titers to nMOG were detected in 40% of children with CIS/ADEM but 0% of the control children affected by other neurological diseases, healthy children, or adults with inflammatory demyelinating diseases, respectively. By contrast, IgM antibodies to nMOG occurred in only 3 children affected by ADEM. Children with high anti-nMOG IgG titer were significantly younger than those with low IgG titer. Anti-nMOG IgG titers did not differ between the ADEM and CIS group, and did not predict conversion from CIS to MS during a mean 2-year follow-up. However, intrathecal IgG anti-MOG antibody synthesis was only seen in CIS children. IgG antibodies to nMOG not only bound to the extracellular domain of nMOG, but also induced natural killer cell-mediated killing of nMOG-expressing cells in vitro. Interpretation Overall, these findings suggest nMOG as a major target of the humoral immune response in a subgroup of children affected by inflammatory demyelinating diseases of the CNS. Children may provide valuable insight into the earliest immune mechanisms of CNS demyelination. Ann Neurol 2009;66:833,842 [source] Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells,ANNALS OF NEUROLOGY, Issue 3 2009Sha Mi PhD Objective Repair of demyelinated axons in diseases such as multiple sclerosis requires activation of the myelination program in existing or newly recruited oligodendrocyte precursor cells (OPCs). The control of OPC differentiation and initiation of myelination during repair is poorly understood. In this study, we test the ability of anti,LINGO-1 reagents to promote myelination in vitro and remyelination in the rodent adult central nervous system in vivo. Methods The effects of LINGO-1 antagonists on the differentiation of OPCs and the promotion of myelination has been assayed using a combination of coculture and slice culture preparations. Using three different animal models of demyelination and remyelination, we morphologically and functionally assessed the effects of LINGO-1 antagonists on OPC differentiation and myelin repair. Results The data indicate that in vitro treatment with antagonists of LINGO-1 promote OPC differentiation and myelination, whereas in vivo remyelination is accelerated in lysophosphatidylcholine- or cuprizone-induced demyelination. This remyelination is associated with enhanced OPC differentiation and functional recovery of conduction velocities in demyelinated axons. Interpretation Our studies demonstrate that LINGO-1 antagonism promotes OPC differentiation and remyelination, and suggest LINGO-1 functions as an inhibitor of OPC differentiation to retard central nervous system remyelination. Ann Neurol 2009;65:304,315 [source] A novel subpopulation of B-1 cells is enriched with autoreactivity in normal and lupus-prone miceARTHRITIS & RHEUMATISM, Issue 12 2009Xuemei Zhong Objective B-1 cells have long been suggested to play an important role in lupus. However, reports to date have been controversial regarding their pathogenic or protective roles in different animal models. We undertook this study to investigate a novel subpopulation of B-1 cells and its roles in murine lupus. Methods Lymphocyte phenotypes were assessed by flow cytometry. Autoantibody secretion was analyzed by enzyme-linked immunosorbent assay, autoantigen proteome array, and antinuclear antibody assay. Cell proliferation was measured by thymidine incorporation and 5,6-carboxyfluorescein succinimidyl ester dilution. B cell Ig isotype switching was measured by enzyme-linked immunospot assay. Results Anti,double-stranded DNA (anti-dsDNA) autoantibodies were preferentially secreted by a subpopulation of CD5+ B-1 cells that expressed programmed death ligand 2 (termed L2pB1 cells). A substantial proportion of hybridoma clones generated from L2pB1 cells reacted to dsDNA. Moreover, these clones were highly cross-reactive with other lupus-related autoantigens. L2pB1 cells were potent antigen-presenting cells and promoted Th17 cell differentiation in vitro. A dramatic increase of circulating L2pB1 cells in lupus-prone BXSB mice was correlated with elevated serum titers of anti-dsDNA antibodies. A significant number of L2pB1 cells preferentially switched to IgG1 and IgG2b when stimulated with interleukin-21. Conclusion Our findings identify a novel subpopulation of B-1 cells that is enriched for autoreactive specificities, undergoes isotype switch, manifests enhanced antigen presentation, promotes Th17 cell differentiation, and is preferentially associated with the development of lupus in a murine model. Together, these findings suggest that L2pB1 cells have the potential to initiate autoimmunity through serologic and T cell,mediated mechanisms. [source] Linking animal models to human congenital diaphragmatic herniaBIRTH DEFECTS RESEARCH, Issue 8 2007Niels Beurskens Abstract BACKGROUND:Congenital diaphragmatic hernia (CDH) is a major life-threatening malformation, occurring in approximately 1 in 3,000 live births. Over the years, different animal models have been used to gain insight into the etiology of this complex congenital anomaly and to develop treatment strategies. However, to date the pathogenic mechanism is still not understood, and treatment remains difficult because of the associated pulmonary hypoplasia and pulmonary hypertension. METHODS: In this review, data available from several animal models will be discussed. The retinoic acid signaling pathway (RA pathway, retinoid pathway) will be addressed as a developmental pathway that is potentially disrupted in the pathogenesis of CDH. Furthermore, genetic factors involved in diaphragm and lung development will be discussed. CONCLUSIONS: With this review article, we aim to provide a concise overview of the current most important experimental genetic data available in the field of CDH. Birth Defects Research (Part A), 2007. © 2007 Wiley-Liss, Inc. [source] Preclinical Studies with Adrenomedullin and Its Binding Protein as Cardiovascular Protective Agents for Hemorrhagic ShockCARDIOVASCULAR THERAPEUTICS, Issue 3-4 2006Rongqian Wu ABSTRACT Traumatic injury is a major, largely unrecognized public health problem in the US that cuts across race, gender, age, and economic boundaries. The resulting loss of productive life years exceeds that of any other disease, with societal costs of $469 billion annually. Most trauma deaths result either from insufficient tissue perfusion due to excessive blood loss, or the development of inflammation, infection, and vital organ damage following resuscitation. Clinical management of hemorrhagic shock relies on massive and rapid infusion of fluids to maintain blood pressure. However, the majority of victims with severe blood loss do not respond well to fluid restoration. The development of effective strategies for resuscitation of traumatic blood loss is therefore critically needed. We have recently discovered that the vascular responsiveness to a recently-discovered potent vasodilatory peptide, adrenomedullin (AM) is depressed after severe blood loss, which may be due to downregulation of a novel specific binding protein, AM binding protein-1 (AMBP-1). Using three different animal models of hemorrhage (controlled hemorrhage with large volume resuscitation, controlled hemorrhage with low volume resuscitation, and uncontrolled hemorrhage with minimum resuscitation), we have shown that cell and organ injury occurs after hemorrhage despite fluid resuscitation. Administration of AM/AMBP-1 significantly improves cardiac output, heart performance and tissue perfusion, attenuates hepatic and renal injury, decreases pro-inflammatory cytokines, prevents metabolic acidosis, and reduces hemorrhage-induced mortality. Thus, administration of AM/AMBP-1 appears to be a novel and useful approach for restoring cardiovascular responses, preventing organ injury, and reducing mortality after hemorrhagic shock. [source] | |||||||||||||||||||||||||