Translational Rodent Models for Research on Parasitic Protozoa-A Review of Confounders and Possibilities.

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Ehret, Totta; Torelli, Francesca; Klotz, Christian; Pedersen, Amy B; Seeber, Frank

2017-01-01

Rodents, in particular Mus musculus , have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents) that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.

Translational Rodent Models for Research on Parasitic Protozoa—A Review of Confounders and Possibilities

Directory of Open Access Journals (Sweden)

Totta Ehret

2017-06-01

Full Text Available Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.

Large Animal Stroke Models vs. Rodent Stroke Models, Pros and Cons, and Combination?

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Cai, Bin; Wang, Ning

2016-01-01

Stroke is a leading cause of serious long-term disability worldwide and the second leading cause of death in many countries. Long-time attempts to salvage dying neurons via various neuroprotective agents have failed in stroke translational research, owing in part to the huge gap between animal stroke models and stroke patients, which also suggests that rodent models have limited predictive value and that alternate large animal models are likely to become important in future translational research. The genetic background, physiological characteristics, behavioral characteristics, and brain structure of large animals, especially nonhuman primates, are analogous to humans, and resemble humans in stroke. Moreover, relatively new regional imaging techniques, measurements of regional cerebral blood flow, and sophisticated physiological monitoring can be more easily performed on the same animal at multiple time points. As a result, we can use large animal stroke models to decrease the gap and promote translation of basic science stroke research. At the same time, we should not neglect the disadvantages of the large animal stroke model such as the significant expense and ethical considerations, which can be overcome by rodent models. Rodents should be selected as stroke models for initial testing and primates or cats are desirable as a second species, which was recommended by the Stroke Therapy Academic Industry Roundtable (STAIR) group in 2009.

Animal models of polycystic ovary syndrome: a focused review of rodent models in relationship to clinical phenotypes and cardiometabolic risk.

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Shi, Danni; Vine, Donna F

2012-07-01

To review rodent animal models of polycystic ovary syndrome (PCOS), with a focus on those associated with the metabolic syndrome and cardiovascular disease risk factors. Review. Rodent models of PCOS. Description and comparison of animal models. Comparison of animal models to clinical phenotypes of PCOS. Animals used to study PCOS include rodents, mice, rhesus monkeys, and ewes. Major methods to induce PCOS in these models include subcutaneous injection or implantation of androgens, estrogens, antiprogesterone, letrozole, prenatal exposure to excess androgens, and exposure to constant light. In addition, transgenic mice models and spontaneous PCOS-like rodent models have also been developed. Rodents are the most economical and widely used animals to study PCOS and ovarian dysfunction. The model chosen to study the development of PCOS and other metabolic parameters remains dependent on the specific etiologic hypotheses being investigated. Rodent models have been shown to demonstrate changes in insulin metabolism, with or without induction of hyperandrogenemia, and limited studies have investigated cardiometabolic risk factors for type 2 diabetes and cardiovascular disease. Given the clinical heterogeneity of PCOS, the utilization of different animal models may be the best approach to further our understanding of the pathophysiologic mechanisms associated with the early etiology of PCOS and cardiometabolic risk. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Lung function and airway inflammation in rats following exposure to combustion products of carbon-graphite/epoxy composite material: comparison to a rodent model of acute lung injury.

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Whitehead, Gregory S; Grasman, Keith A; Kimmel, Edgar C

2003-02-01

Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the

Rodent models of congenital and hereditary cataract in man.

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Tripathi, B J; Tripathi, R C; Borisuth, N S; Dhaliwal, R; Dhaliwal, D

1991-01-01

Because the organogenesis and physiology of the lens are essentially similar in various mammals, an understanding of the etiology and pathogenesis of the formation of cataract in an animal model will enhance our knowledge of cataractogenesis in man. In this review, we summarize the background, etiology, and pathogenesis of cataracts that occur in rodents. The main advantages of using rodent mutants include the well-researched genetics of the animals and the comparative ease of breeding of large litters. Numerous rodent models of congenital and hereditary cataracts have been studied extensively. In mice, the models include the Cts strain, Fraser mouse, lens opacity gene (Lop) strain, Lop-2 and Lop-3 strains, Philly mouse, Nakano mouse, Nop strain, Deer mouse, Emory mouse, Swiss Webster strain, Balb/c-nct/nct mouse, and SAM-R/3 strain. The rat models include BUdR, ICR, Sprague-Dawley, and Wistar rats, the spontaneously hypertensive rat (SHR), the John Rapp inbred strain of Dahl salt-sensitive rat, as well as WBN/Kob, Royal College of Surgeons (RCS), and Brown-Norway rats. Other proposed models for the study of hereditary cataract include the degu and the guinea pig. Because of the ease of making clinical observations in vivo and the subsequent availability of the intact lens for laboratory analyses at different stages of cataract formation, these animals provide excellent models for clinicopathologic correlations, for monitoring of the natural history of the aging process and of metabolic defects, as well as for investigations on the effect of cataract-modulating agents and drugs, including the prospect of gene therapy.

Two new rodent models for actinide toxicity studies

International Nuclear Information System (INIS)

Taylor, G.N.; Jones, C.W.; Gardner, P.A.; Lloyd, R.D.; Mays, C.W.; Charrier, K.E.

1981-01-01

Two small rodent species, the grasshopper mouse (Onychomys leucogaster) and the deer mouse (Peromyscus maniculatus), have tenacious and high retention in the liver and skeleton of plutonium and americium following intraperitoneal injection of Pu and Am in citrate solution. Liver retention of Pu and Am in the grasshopper mouse is higher than liver retention in the deer mouse. Both of these rodents are relatively long-lived, breed well in captivity, and adapt suitably to laboratory conditions. It is suggested that these two species of mice, in which plutonium retention is high and prolonged in both the skeleton and liver, as it is in man, may be useful animal models for actinide toxicity studies

Acute and subacute oral toxicity evaluation of Tephrosia purpurea extract in rodents

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Talib Hussain

2012-04-01

Full Text Available Objective: To evaluate the acute and subacute toxicity of 50% ethanolic extract of Tephrosia purpurea (T. purpurea in rodents. Methods: The acute toxicity test was conducted in Swiss albino mice. The extract of T. purpurea was administrated in single doses of 50, 300 and 2000 mg/ kg and observed for behavioral changes and mortality, if any. In subacute toxicity study, Wistar rats of either sex were administered two doses of T. purpurea i.e., 200 and 400 mg/kg (One-tenth and one-fifth of the maximum tolerated dose, p.o. for 4 weeks. During 28 days of treatment, rats were observed weekly for any change in their body weight, food and water intake. At the end of 28 days, rats were sacrificed for hematological, biochemical and histopathology study. Results: In the acute toxicity study, T. purpurea was found to be well tolerated upto 2 000 mg/kg, produced neither mortality nor changes in behavior in mice. In subacute toxicity study, T. purpurea at dose level of 200 and 400 mg/kg did not produce any significant difference in their body weight, food and water intake when compared to vehicle treated rats. It also showed no significant alteration in hematological and biochemical parameters in experimental groups of rats apart from a decrease in aspartate transaminase, alanine transaminase and alkaline phosphate content at the dose of 400 mg/kg. Histopathological study revealed normal architecture of kidney and liver of T. purpurea treated rats. Conclusions: These results demonstrated that there is a wide margin of safety for the therapeutic use of T. purpurea and further corroborated the traditional use of this extract as an anti hepatocarcinogenic agent

Optimizing Cardiovascular Benefits of Exercise: A Review of Rodent Models

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Davis, Brittany; Moriguchi, Takeshi; Sumpio, Bauer

2013-01-01

Although research unanimously maintains that exercise can ward off cardiovascular disease (CVD), the optimal type, duration, intensity, and combination of forms are yet not clear. In our review of existing rodent-based studies on exercise and cardiovascular health, we attempt to find the optimal forms, intensities, and durations of exercise. Using Scopus and Medline, a literature review of English language comparative journal studies of cardiovascular benefits and exercise was performed. This review examines the existing literature on rodent models of aerobic, anaerobic, and power exercise and compares the benefits of various training forms, intensities, and durations. The rodent studies reviewed in this article correlate with reports on human subjects that suggest regular aerobic exercise can improve cardiac and vascular structure and function, as well as lipid profiles, and reduce the risk of CVD. Findings demonstrate an abundance of rodent-based aerobic studies, but a lack of anaerobic and power forms of exercise, as well as comparisons of these three components of exercise. Thus, further studies must be conducted to determine a truly optimal regimen for cardiovascular health. PMID:24436579

Of mice and women: rodent models of placental malaria

DEFF Research Database (Denmark)

Hviid, Lars; Marinho, Claudio R F; Staalsoe, Trine

2010-01-01

Pregnant women are at increased malaria risk. The infections are characterized by placental accumulation of infected erythrocytes (IEs) with adverse consequences for mother and baby. Placental IE sequestration in the intervillous space is mediated by variant surface antigens (VSAs) selectively...... expressed in placental malaria (PM) and specific for chondroitin sulfate A (CSA). In Plasmodium falciparum, these VSA(PM) appear largely synonymous with the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family variant VAR2CSA. As rodent malaria parasites do not possess PfEMP1 homologs......, the usefulness of experimental mouse PM models remains controversial. However, many features of murine and human PM are similar, including involvement of VSAs analogous to PfEMP1. It thus appears that rodent model studies can further the understanding of VSA-dependent malaria pathogenesis and immunity....

Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury.

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MacManes, Matthew David

2017-08-01

Animals living in desert environments are forced to survive despite severe heat, intense solar radiation, and both acute and chronic dehydration. These animals have evolved phenotypes that effectively address these environmental stressors. To begin to understand the ways in which the desert-adapted rodent Peromyscus eremicus survives, reproductively mature adults were subjected to 72 h of water deprivation, during which they lost, on average, 23% of their body weight. The animals reacted via a series of changes in the kidney, which included modulating expression of genes responsible for reducing the rate of transcription and maintaining water and salt balance. Extracellular matrix turnover appeared to be decreased, and apoptosis was limited. In contrast to the canonical human response, serum creatinine and other biomarkers of kidney injury were not elevated, suggesting that changes in gene expression related to acute dehydration may effectively prohibit widespread kidney damage in the cactus mouse. Copyright © 2017 the American Physiological Society.

Analgesic and Anti-Inflammatory Effects of 80% Methanol Extract of Leonotis ocymifolia (Burm.f. Iwarsson Leaves in Rodent Models

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Asnakech Alemu

2018-01-01

Full Text Available Background. Pain and inflammation are the major health problems commonly treated with traditional remedies mainly using medicinal plants. Leonotis ocymifolia is one of such medicinal plants used in folkloric medicine of Ethiopia. However, the plant has not been scientifically evaluated. The aim of this study was to evaluate analgesic and anti-inflammatory effects of the 80% methanol leaves extract of Leonotis ocymifolia using rodent models. Method. The central and peripheral analgesic effect of the extract at 100, 200, and 400 mg/kg dose levels was evaluated using hot plate and acetic acid induced writhing rodent models, whereas carrageenan induced paw edema and cotton pellet granuloma methods were used to screen anti-inflammatory effect of the extract at the same dose levels. Acute toxicity test was also done. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test and p<0.05 was considered significant. Results. The extract did not produce mortality up to 2000 mg/kg. All tested doses of the extract showed significant analgesic effect with maximum latency response of 62.8% and inhibition of acetic acid induced writhing. Maximum anti-inflammatory effect was recorded at 6 h after induction, with 75.88% reduction in carrageenan induced paw edema. Moreover, all tested doses of extract significantly inhibited the formation of inflammatory exudates and granuloma formation (p<0.001. Conclusion. The study indicated that the extract was safe in mice and it has both analgesic and anti-inflammatory effect in rodent models.

Rodent Models of Alcoholic Liver Disease: Role of Binge Ethanol Administration

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Shubha Ghosh Dastidar

2018-01-01

Full Text Available Both chronic and acute (binge alcohol drinking are important health and economic concerns worldwide and prominent risk factors for the development of alcoholic liver disease (ALD. There are no FDA-approved medications to prevent or to treat any stage of ALD. Therefore, discovery of novel therapeutic strategies remains a critical need for patients with ALD. Relevant experimental animal models that simulate human drinking patterns and mimic the spectrum and severity of alcohol-induced liver pathology in humans are critical to our ability to identify new mechanisms and therapeutic targets. There are several animal models currently in use, including the most widely utilized chronic ad libitum ethanol (EtOH feeding (Lieber–DeCarli liquid diet model, chronic intragastric EtOH administration (Tsukamoto–French model, and chronic-plus-binge EtOH challenge (Bin Gao—National Institute on Alcohol Abuse and Alcoholism (NIAAA model. This review provides an overview of recent advances in rodent models of binge EtOH administration which help to recapitulate different features and etiologies of progressive ALD. These models include EtOH binge alone, and EtOH binge coupled with chronic EtOH intake, a high fat diet, or endotoxin challenge. We analyze the strengths, limitations, and translational relevance of these models, as well as summarize the liver injury outcomes and mechanistic insights. We further discuss the application(s of binge EtOH models in examining alcohol-induced multi-organ pathology, sex- and age-related differences, as well as circadian rhythm disruption.

Integrative rodent models for assessing male reproductive toxicity of environmental endocrine active substances

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Jacques Auger

2014-02-01

Full Text Available In the present review, we first summarize the main benefits, limitations and pitfalls of conventional in vivo approaches to assessing male reproductive structures and functions in rodents in cases of endocrine active substance (EAS exposure from the postulate that they may provide data that can be extrapolated to humans. Then, we briefly present some integrated approaches in rodents we have recently developed at the organism level. We particularly focus on the possible effects and modes of action (MOA of these substances at low doses and in mixtures, real-life conditions and at the organ level, deciphering the precise effects and MOA on the fetal testis. It can be considered that the in vivo experimental EAS exposure of rodents remains the first choice for studies and is a necessary tool (together with the epidemiological approach for understanding the reproductive effects and MOA of EASs, provided the pitfalls and limitations of the rodent models are known and considered. We also provide some evidence that classical rodent models may be refined for studying the multiple consequences of EAS exposure, not only on the reproductive axis but also on various hormonally regulated organs and tissues, among which several are implicated in the complex process of mammalian reproduction. Such models constitute an interesting way of approaching human exposure conditions. Finally, we show that organotypic culture models are powerful complementary tools, especially when focusing on the MOA. All these approaches have contributed in a combinatorial manner to a better understanding of the impact of EAS exposure on human reproduction.

Studying autism in rodent models: reconciling endophenotypes with comorbidities.

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Andrew eArgyropoulos

2013-07-01

Full Text Available Autism spectrum disorder (ASD patients commonly exhibit a variety of comorbid traits including seizures, anxiety, aggressive behavior, gastrointestinal problems, motor deficits, abnormal sensory processing and sleep disturbances for which the cause is unknown. These features impact negatively on daily life and can exaggerate the effects of the core diagnostic traits (social communication deficits and repetitive behaviors. Studying endophenotypes relevant to both core and comorbid features of ASD in rodent models can provide insight into biological mechanisms underlying these disorders. Here we review the characterization of endophenotypes in a selection of environmental, genetic and behavioural rodent models of ASD. In addition to exhibiting core ASD-like behaviours, each of these animal models display one or more endophenotypes relevant to comorbid features including altered sensory processing, seizure susceptibility, anxiety-like behaviour and disturbed motor functions, suggesting that these traits are indicators of altered biological pathways in ASD. However, the study of behaviours paralleling comorbid traits in animal models of ASD is an emerging field and further research is needed to assess altered gastrointestinal function, aggression and disorders of sleep onset across models. Future studies should include investigation of these endophenotypes in order to advance our understanding of the etiology of this complex disorder.

New Insights from Rodent Models of Fatty Liver Disease

Science.gov (United States)

2011-01-01

Abstract Rodent models of fatty liver disease are essential research tools that provide a window into disease pathogenesis and a testing ground for prevention and treatment. Models come in many varieties involving dietary and genetic manipulations, and sometimes both. High-energy diets that induce obesity do not uniformly cause fatty liver disease; this has prompted close scrutiny of specific macronutrients and nutrient combinations to determine which have the greatest potential for hepatotoxicity. At the same time, diets that do not cause obesity or the metabolic syndrome but do cause severe steatohepatitis have been exploited to study factors important to progressive liver injury, including cell death, oxidative stress, and immune activation. Rodents with a genetic predisposition to overeating offer yet another model in which to explore the evolution of fatty liver disease. In some animals that overeat, steatohepatitis can develop even without resorting to a high-energy diet. Importantly, these models and others have been used to document that aerobic exercise can prevent or reduce fatty liver disease. This review focuses primarily on lessons learned about steatohepatitis from manipulations of diet and eating behavior. Numerous additional insights about hepatic lipid metabolism, which have been gained from genetically engineered mice, are also mentioned. Antioxid. Redox Signal. 15, 535–550. PMID:21126212

Plasmalemmal Vesicle Associated Protein-1 (PV-1 is a marker of blood-brain barrier disruption in rodent models

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Ali Zarina S

2008-02-01

Full Text Available Abstract Background Plasmalemmal vesicle associated protein-1 (PV-1 is selectively expressed in human brain microvascular endothelial cells derived from clinical specimens of primary and secondary malignant brain tumors, cerebral ischemia, and other central nervous system (CNS diseases associated with blood-brain barrier breakdown. In this study, we characterize the murine CNS expression pattern of PV-1 to determine whether localized PV-1 induction is conserved across species and disease state. Results We demonstrate that PV-1 is selectively upregulated in mouse blood vessels recruited by brain tumor xenografts at the RNA and protein levels, but is not detected in non-neoplastic brain. Additionally, PV-1 is induced in a mouse model of acute ischemia. Expression is confined to the cerebovasculature within the region of infarct and is temporally regulated. Conclusion Our results confirm that PV-1 is preferentially induced in the endothelium of mouse brain tumors and acute ischemic brain tissue and corresponds to blood-brain barrier disruption in a fashion analogous to human patients. Characterization of PV-1 expression in mouse brain is the first step towards development of rodent models for testing anti-edema and anti-angiogenesis therapeutic strategies based on this molecule.

STRESS INDUCED OBESITY: LESSONS FROM RODENT MODELS OF STRESS

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Zachary Robert Patterson

2013-07-01

Full Text Available Stress is defined as the behavioral and physiological responses generated in the face of, or in anticipation of, a perceived threat. The stress response involves activation of the sympathetic nervous system and recruitment of the hypothalamic-pituitary-adrenal (HPA axis. When an organism encounters a stressor (social, physical, etc., these endogenous stress systems are stimulated in order to generate a fight-or-flight response, and manage the stressful situation. As such, an organism is forced to liberate energy resources in attempt to meet the energetic demands posed by the stressor. A change in the energy homeostatic balance is thus required to exploit an appropriate resource and deliver useable energy to the target muscles and tissues involved in the stress response. Acutely, this change in energy homeostasis and the liberation of energy is considered advantageous, as it is required for the survival of the organism. However, when an organism is subjected to a prolonged stressor, as is the case during chronic stress, a continuous irregularity in energy homeostasis is considered detrimental and may lead to the development of metabolic disturbances such as cardiovascular disease, type II diabetes mellitus and obesity. This concept has been studied extensively using animal models, and the neurobiological underpinnings of stress induced metabolic disorders are beginning to surface. However, different animal models of stress continue to produce divergent metabolic phenotypes wherein some animals become anorexic and loose body mass while others increase food intake and body mass and become vulnerable to the development of metabolic disturbances. It remains unclear exactly what factors associated with stress models can be used to predict the metabolic outcome of the organism. This review will explore a variety of rodent stress models and discuss the elements that influence the metabolic outcome in order to further our understanding of stress

Acute Inhalation Toxicity and Blood Absorption of 2,4-Dinitroanisole (DNAN) in Rats

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2015-03-17

light/dark cycle. A certified pesticide -free rodent chow (Harlan Teklad ® , 8728C Certified Rodent Diet) and drinking quality water were available ad...respiration, toxicity, blood, concentration, alternative, welfare, method, model, in vitro, pain, distress, simulate, video , computer, replacement, refinement...Prevention, Pesticides , and Toxic Substances. December 2002. Health Effects Test Guidelines: OPPTS 870.1000, Acute Toxicity Testing - Background. EPA

A rodent malarial model of Plasmodium berghei for the development ...

African Journals Online (AJOL)

A rodent malarial model of Plasmodium berghei for the development of pyrimethamine and sulphadoxine-pyrimethamine resistant malaria in mice. ... course approach with 125/6.25mg/kg S/P. The stability of resistance phenotypes, parasite pathogenic disposition and host leukocyte response were also investigated.

Spatial memory tasks in rodents: what do they model?

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Morellini, Fabio

2013-10-01

The analysis of spatial learning and memory in rodents is commonly used to investigate the mechanisms underlying certain forms of human cognition and to model their dysfunction in neuropsychiatric and neurodegenerative diseases. Proper interpretation of rodent behavior in terms of spatial memory and as a model of human cognitive functions is only possible if various navigation strategies and factors controlling the performance of the animal in a spatial task are taken into consideration. The aim of this review is to describe the experimental approaches that are being used for the study of spatial memory in rats and mice and the way that they can be interpreted in terms of general memory functions. After an introduction to the classification of memory into various categories and respective underlying neuroanatomical substrates, I explain the concept of spatial memory and its measurement in rats and mice by analysis of their navigation strategies. Subsequently, I describe the most common paradigms for spatial memory assessment with specific focus on methodological issues relevant for the correct interpretation of the results in terms of cognitive function. Finally, I present recent advances in the use of spatial memory tasks to investigate episodic-like memory in mice.

New Perspectives on Rodent Models of Advanced Paternal Age: Relevance to Autism

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Claire J Foldi

2011-06-01

Full Text Available Offspring of older fathers have an increased risk of various adverse health outcomes, including autism and schizophrenia. With respect to biological mechanisms for this association, there are many more germline cell divisions in the life history of a sperm relative to that of an oocyte. This leads to more opportunities for copy error mutations in germ cells from older fathers. Evidence also suggests that epigenetic patterning in the sperm from older men is altered. Rodent models provide an experimental platform to examine the association between paternal age and brain development. Several rodent models of advanced paternal age (APA have been published with relevance to intermediate phenotypes related to autism. All four published APA models vary in key features creating a lack of consistency with respect to behavioural phenotypes. A consideration of common phenotypes that emerge from these APA-related mouse models may be informative in the exploration of the molecular and neurobiological correlates of APA.

Functional recovery after facial nerve cable grafting in a rodent model.

NARCIS (Netherlands)

Hohman, M.H.; Kleiss, I.J.; Knox, C.J.; Weinberg, J.S.; Heaton, J.T.; Hadlock, T.A.

2014-01-01

IMPORTANCE: Cable grafting is widely considered to be the preferred alternative to primary repair of the injured facial nerve; however, quantitative comparison of the 2 techniques has not been previously undertaken in a rodent model. OBJECTIVE: To establish functional recovery parameters after

The relevance of non-human primate and rodent malaria models for humans

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Riley Eleanor

2011-02-01

Full Text Available Abstract At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material.

Stimulant and motivational effects of alcohol: lessons from rodent and primate models.

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Brabant, Christian; Guarnieri, Douglas J; Quertemont, Etienne

2014-07-01

In several animal species including humans, the acute administration of low doses of alcohol increases motor activity. Different theories have postulated that alcohol-induced hyperactivity is causally related to alcoholism. Moreover, a common biological mechanism in the mesolimbic dopamine system has been proposed to mediate the stimulant and motivational effects of alcohol. Numerous studies have examined whether alcohol-induced hyperactivity is related to alcoholism using a great variety of animal models and several animal species. However, there is no review that has summarized this extensive literature. In this article, we present the various experimental models that have been used to study the relationship between the stimulant and motivational effects of alcohol in rodents and primates. Furthermore, we discuss whether the theories hypothesizing a causal link between alcohol-induced hyperactivity and alcoholism are supported by published results. The reviewed findings indicate that animal species that are stimulated by alcohol also exhibit alcohol preference. Additionally, the role of dopamine in alcohol-induced hyperactivity is well established since blocking dopaminergic activity suppresses the stimulant effects of alcohol. However, dopamine transmission plays a much more complex function in the motivational properties of alcohol and the neuronal mechanisms involved in alcohol stimulation and reward are distinct. Overall, the current review provides mixed support for theories suggesting that the stimulant effects of alcohol are related to alcoholism and highlights the importance of animal models as a way to gain insight into alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

A model of Leptospirosis infection in an African rodent to determine risk to humans: Seasonal fluctuations and the impact of rodent control

DEFF Research Database (Denmark)

Holt, J; Davis, S; Leirs, Herwig

2006-01-01

Human leptospirosis (Leptospira spp. infection) is aworldwide public health problem that is of greatest concern for humid tropical and subtropical regions. The magnitude of the problem in these areas is larger because of the climatic and environmental conditions the bacterium face outside...... their hosts but also because of the frequency of contacts between people and sources of infection. Rodents are thought to play the most important role in the transmission of human leptospirosis. We here model the dynamics of infection in an African rodent (Mastomys natalensis) that is thought...... to be the principal source of infection in parts of Tanzania. Our model, representing the climatic conditions in central Tanzania, suggests a strong seasonality in the force of infection on humans with a peak in the abundance of infectious mice between January and April in agricultural environments. In urban areas...

Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain.

Directory of Open Access Journals (Sweden)

Michael R Due

Full Text Available Approximately 60% of morphine is glucuronidated to morphine-3-glucuronide (M3G which may aggravate preexisting pain conditions. Accumulating evidence indicates that M3G signaling through neuronal Toll-like receptor 4 (TLR4 may be central to this proalgesic signaling event. These events are known to include elevated neuronal excitability, increased voltage-gated sodium (NaV current, tactile allodynia and decreased opioid analgesic efficacy. Using an in vitro ratiometric-based calcium influx analysis of acutely dissociated small and medium-diameter neurons derived from lumbar dorsal root ganglion (DRG, we observed that M3G-sensitive neurons responded to lipopolysaccharide (LPS and over 35% of these M3G/LPS-responsive cells exhibited sensitivity to capsaicin. In addition, M3G-exposed sensory neurons significantly increased excitatory activity and potentiated NaV current as measured by current and voltage clamp, when compared to baseline level measurements. The M3G-dependent excitability and potentiation of NaV current in these sensory neurons could be reversed by the addition of carbamazepine (CBZ, a known inhibitor of several NaV currents. We then compared the efficacy between CBZ and morphine as independent agents, to the combined treatment of both drugs simultaneously, in the tibial nerve injury (TNI model of neuropathic pain. The potent anti-nociceptive effects of morphine (5 mg/kg, i.p. were observed in TNI rodents at post-injury day (PID 7-14 and absent at PID21-28, while administration of CBZ (10 mg/kg, i.p. alone failed to produce anti-nociceptive effects at any time following TNI (PID 7-28. In contrast to either drug alone at PID28, the combination of morphine and CBZ completely attenuated tactile hyperalgesia in the rodent TNI model. The basis for the potentiation of morphine in combination with CBZ may be due to the effects of a latent upregulation of NaV1.7 in the DRG following TNI. Taken together, our observations demonstrate a

Temporal and Spatial Characterization of Gait Pattern in Rodents as an Animal model of Cerebrovascular Lesion

Directory of Open Access Journals (Sweden)

Jaison D Cucarián

2017-09-01

Full Text Available Animal experimentation is crucial for the advance in the understanding of pathophysiological mechanisms and their application on both clinical diagnosis and neuro-rehabilitation. Particularly, rodent brain lesion is commonly used in the modeling of locomotor, somatosensory and cognitive symptoms. The automated rodent gait analysis has been proposed as a tool for studying locomotor and sensory abilities and its use includes the identification of functional alterations, structural adaptations as well as neuro-rehabilitation mechanisms. From that standpoint, the effectiveness of many therapeutic intervention (i.e. physical exercises has been documented in rodents and humans. The translation from experimental data to clinical conditions requires the continuous collaboration and feedback between researchers and health clinicians looking for the selection of the best rehabilitation protocols obtained from animal research. Here we will show some locomotor alterations, the traditional methods used to assess motor dysfunction and gait abnormalities in rodent models with stroke. The aim of this review is to show some motor deficiencies and some methods used to establish gait disturbances in rodents with cerebrovascular lesion. The review included the search of defined terms (MeSH in PychINFO, Medline and Web of Science, between January 2000 and January 2017. Qualitative and narrative reports, dissertations, end course works and conference resumes were discarded. The review focuses on some clinical signs, their effects on rodent locomotor activity, some methodologies used to create lesion and to study motor function, some assessment methods and some translational aspects.

Genetic Rodent Models of Obesity-Associated Ovarian Dysfunction and Subfertility: Insights into Polycystic Ovary Syndrome

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Huang-Doran, Isabel; Franks, Stephen

2016-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women and a leading cause of female infertility worldwide. Defined clinically by the presence of hyperandrogenemia and oligomenorrhoea, PCOS represents a state of hormonal dysregulation, disrupted ovarian follicle dynamics, and subsequent oligo- or anovulation. The syndrome’s prevalence is attributed, at least partly, to a well-established association with obesity and insulin resistance (IR). Indeed, the presence of severe PCOS in human genetic obesity and IR syndromes supports a causal role for IR in the pathogenesis of PCOS. However, the molecular mechanisms underlying this causality, as well as the important role of hyperandrogenemia, remain poorly elucidated. As such, treatment of PCOS is necessarily empirical, focusing on symptom alleviation. The generation of knockout and transgenic rodent models of obesity and IR offers a promising platform in which to address mechanistic questions about reproductive dysfunction in the context of metabolic disease. Similarly, the impact of primary perturbations in rodent gonadotrophin or androgen signaling has been interrogated. However, the insights gained from such models have been limited by the relatively poor fidelity of rodent models to human PCOS. In this mini review, we evaluate the ovarian phenotypes associated with rodent models of obesity and IR, including the extent of endocrine disturbance, ovarian dysmorphology, and subfertility. We compare them to both human PCOS and other animal models of the syndrome (genetic and hormonal), explore reasons for their discordance, and consider the new opportunities that are emerging to better understand and treat this important condition. PMID:27375552

Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.

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Sweeney, Timothy E; Lofgren, Shane; Khatri, Purvesh; Rogers, Angela J

2017-08-01

The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

Vagus nerve stimulation inhibits trigeminal nociception in a rodent model of episodic migraine

Directory of Open Access Journals (Sweden)

Jordan L. Hawkins

2017-12-01

Conclusion:. Our findings demonstrate that nVNS inhibits mechanical nociception and represses expression of proteins associated with peripheral and central sensitization of trigeminal neurons in a novel rodent model of episodic migraine.

Morphological and functional maturation of Leydig cells: from rodent models to primates.

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Teerds, Katja J; Huhtaniemi, Ilpo T

2015-01-01

Leydig cells (LC) are the sites of testicular androgen production. Development of LC occurs in the testes of most mammalian species as two distinct growth phases, i.e. as fetal and pubertal/adult populations. In primates there are indications of a third neonatal growth phase. LC androgen production begins in embryonic life and is crucial for the intrauterine masculinization of the male fetal genital tract and brain, and continues until birth after which it rapidly declines. A short post-natal phase of LC activity in primates (including human) termed 'mini-puberty' precedes the period of juvenile quiescence. The adult population of LC evolves, depending on species, in mid- to late-prepuberty upon reawakening of the hypothalamic-pituitary-testicular axis, and these cells are responsible for testicular androgen production in adult life, which continues with a slight gradual decline until senescence. This review is an updated comparative analysis of the functional and morphological maturation of LC in model species with special reference to rodents and primates. Pubmed, Scopus, Web of Science and Google Scholar databases were searched between December 2012 and October 2014. Studies published in languages other than English or German were excluded, as were data in abstract form only. Studies available on primates were primarily examined and compared with available data from specific animal models with emphasis on rodents. Expression of different marker genes in rodents provides evidence that at least two distinct progenitor lineages give rise to the fetal LC (FLC) population, one arising from the coelomic epithelium and the other from specialized vascular-associated cells along the gonad-mesonephros border. There is general agreement that the formation and functioning of the FLC population in rodents is gonadotrophin-responsive but not gonadotrophin-dependent. In contrast, although there is in primates some controversy on the role of gonadotrophins in the formation of

Kynurenine-3-monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis.

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Mole, Damian J; Webster, Scott P; Uings, Iain; Zheng, Xiaozhong; Binnie, Margaret; Wilson, Kris; Hutchinson, Jonathan P; Mirguet, Olivier; Walker, Ann; Beaufils, Benjamin; Ancellin, Nicolas; Trottet, Lionel; Bénéton, Véronique; Mowat, Christopher G; Wilkinson, Martin; Rowland, Paul; Haslam, Carl; McBride, Andrew; Homer, Natalie Z M; Baily, James E; Sharp, Matthew G F; Garden, O James; Hughes, Jeremy; Howie, Sarah E M; Holmes, Duncan S; Liddle, John; Iredale, John P

2016-02-01

Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death. Acute mortality from AP-MODS exceeds 20% (ref. 3), and the lifespans of those who survive the initial episode are typically shorter than those of the general population. There are no specific therapies available to protect individuals from AP-MODS. Here we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism, is central to the pathogenesis of AP-MODS. We created a mouse strain that is deficient for Kmo (encoding KMO) and that has a robust biochemical phenotype that protects against extrapancreatic tissue injury to the lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of the oxazolidinone GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Å resolution. Treatment with GSK180 resulted in rapid changes in the levels of kynurenine pathway metabolites in vivo, and it afforded therapeutic protection against MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS, and they open up a new area for drug discovery in critical illness.

The relevance of non-human primate and rodent malaria models for humans

OpenAIRE

Langhorne, Jean; Buffet, Pierre; Galinski, Mary; Good, Michael; Harty, John; Leroy, Didier; Mota, Maria M; Pasini, Erica; Renia, Laurent; Riley, Eleanor; Stins, Monique; Duffy, Patrick

2011-01-01

Abstract At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models....

Modeling Human Nonalcoholic Steatohepatitis-Associated Changes in Drug Transporter Expression Using Experimental Rodent Models

OpenAIRE

Canet, Mark J.; Hardwick, Rhiannon N.; Lake, April D.; Dzierlenga, Anika L.; Clarke, John D.; Cherrington, Nathan J.

2014-01-01

Nonalcoholic fatty liver disease is a prevalent form of chronic liver disease that can progress to the more advanced stage of nonalcoholic steatohepatitis (NASH). NASH has been shown to alter drug transporter regulation and may have implications in the development of adverse drug reactions. Several experimental rodent models have been proposed for the study of NASH, but no single model fully recapitulates all aspects of the human disease. The purpose of the current study was to determine whic...

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

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Musah, Sadiatu; Schlueter, Connie F.; Humphrey, David M. [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Powell, Karen S. [Research Resource Facilities, University of Louisville, Louisville, KY (United States); Roberts, Andrew M. [Department of Physiology, University of Louisville, Louisville, KY (United States); Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States)

2017-01-15

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure–volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. - Highlights: • A novel rabbit model of chlorine-induced lung disease was developed. �

Neurobiology of rodent self-grooming and its value for translational neuroscience.

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Kalueff, Allan V; Stewart, Adam Michael; Song, Cai; Berridge, Kent C; Graybiel, Ann M; Fentress, John C

2016-01-01

Self-grooming is a complex innate behaviour with an evolutionarily conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self-grooming, and we highlight studies of rodent models of neuropsychiatric disorders--including models of autism spectrum disorder and obsessive compulsive disorder--that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action.

Chronic and acute effects of stress on energy balance: are there appropriate animal models?

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Harris, Ruth B S

2015-02-15

Stress activates multiple neural and endocrine systems to allow an animal to respond to and survive in a threatening environment. The corticotropin-releasing factor system is a primary initiator of this integrated response, which includes activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. The energetic response to acute stress is determined by the nature and severity of the stressor, but a typical response to an acute stressor is inhibition of food intake, increased heat production, and increased activity with sustained changes in body weight, behavior, and HPA reactivity. The effect of chronic psychological stress is more variable. In humans, chronic stress may cause weight gain in restrained eaters who show increased HPA reactivity to acute stress. This phenotype is difficult to replicate in rodent models where chronic psychological stress is more likely to cause weight loss than weight gain. An exception may be hamsters subjected to repeated bouts of social defeat or foot shock, but the data are limited. Recent reports on the food intake and body composition of subordinate members of group-housed female monkeys indicate that these animals have a similar phenotype to human stress-induced eaters, but there are a limited number of investigators with access to the model. Few stress experiments focus on energy balance, but more information on the phenotype of both humans and animal models during and after exposure to acute or chronic stress may provide novel insight into mechanisms that normally control body weight. Copyright © 2015 the American Physiological Society.

Sub-processes of motor learning revealed by a robotic manipulandum for rodents.

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Lambercy, O; Schubring-Giese, M; Vigaru, B; Gassert, R; Luft, A R; Hosp, J A

2015-02-01

Rodent models are widely used to investigate neural changes in response to motor learning. Usually, the behavioral readout of motor learning tasks used for this purpose is restricted to a binary measure of performance (i.e. "successful" movement vs. "failure"). Thus, the assignability of research in rodents to concepts gained in human research - implying diverse internal models that constitute motor learning - is still limited. To solve this problem, we recently introduced a three-degree-of-freedom robotic platform designed for rats (the ETH-Pattus) that combines an accurate behavioral readout (in the form of kinematics) with the possibility to invasively assess learning related changes within the brain (e.g. by performing immunohistochemistry or electrophysiology in acute slice preparations). Here, we validate this platform as a tool to study motor learning by establishing two forelimb-reaching paradigms that differ in degree of skill. Both conditions can be precisely differentiated in terms of their temporal pattern and performance levels. Based on behavioral data, we hypothesize the presence of several sub-processes contributing to motor learning. These share close similarities with concepts gained in humans or primates. Copyright © 2014 Elsevier B.V. All rights reserved.

Antinociceptive activity of novel amide derivatives of imidazolidine-2,4-dione in a mouse model of acute pain.

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Czopek, Anna; Sałat, Kinga; Byrtus, Hanna; Rychtyk, Joanna; Pawłowski, Maciej; Siwek, Agata; Soluch, Joanna; Mureddu, Valentina; Filipek, Barbara

2016-06-01

Antiepileptic drugs are commonly used in non-epileptic disorders. For example, phenytoin and levetiracetam demonstrate analgesic properties in rodent models of pain. In order to enhance their antinociceptive activity, structural features of phenytoin and levetiracetam, such as imidazolidine-2,4-dione and amide bond in alkyl chain, were combined in one molecule. Furthermore, in preliminary studies, methoxyphenylpiperazinpropyl derivatives of imidazolidine-2,4-dione acted as antinociceptive agents in several rodent models of acute pain. The final compounds and the reference drugs - levetiracetam and phenytoin were evaluated in the hot plate test to assess their antinociceptive activity in this acute pain model. Furthermore, for the analgesic active compounds the impact on animals' locomotor activity and motor performance were estimated and the affinity to serotonergic (5-HT1A, 5-HT7) and adrenergic (α1) receptors was determined. Three of the tested compounds: 7, 15 and 18 showed statistically significant antinociceptive properties at the dose of 30mg/kg. Among them, compound 18, 1-methyl-3-[1-(morpholin-4-yl)-1-oxobutan-2-yl]imidazolidine-2,4-dione, exhibited the most significant and long-lasting antinociceptive activity. Noteworthy, this activity was not associated with a negative effect on animals' motor functions. Serotonergic or adrenergic neurotransmission is not involved in this antinociceptive effect. Some amide derivatives of imidazolidine-2,4-diones possess antinociceptive properties in mice but further studies are needed to explain their mechanism of action and assess their toxicity. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Piper umbellatum L.: A medicinal plant with gastric-ulcer protective and ulcer healing effects in experimental rodent models.

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da Silva Junior, Iberê Ferreira; Balogun, Sikiru Olaitan; de Oliveira, Ruberlei Godinho; Damazo, Amílcar Sabino; Martins, Domingos Tabajara de Oliveira

2016-11-04

Piper umbellatum L. (Piperaceae) is a shrub found in the Amazon, Savannah and Atlantic Forest region of Brazil. It is widely used in folk medicine in many countries primarily for the treatment of gastric disorders. The aim of this study was to evaluate the gastroprotective and anti-ulcer effects of hydroethanolic extract of P. umbellatum (HEPu) leaves in experimental rodents. In addition, the anti-Helicobacter pylori activity of the extract was assessed. The leaves of P. umbellatum were macerated in 75% (1:3w/v) hydroethanolic solution to obtain HEPu. The gastroprotective and ulcer healing activities of HEPu were evaluated using acidified ethanol (acute) and acetic acid (chronic) gastric ulcer models in rodents. The anti-H. pylori activity was evaluated by in vitro broth microdilution assay using H. pylori cagA + and vacA + strain. The probable mechanism of action of HEPu was evaluated by determining gastric secretory parameters, antioxidant enzyme (catalase), non-protein sulfhydryl (glutathione) and malondialdehyde levels in gastric tissue, including pro-inflammatory (IL-1β, TNF-a, IL -17, RANTES, IFN-γ and MIP-2) and anti-inflammatory (IL-10) cytokines. HEPu demonstrated potent gastroprotection against acute ulcer induced by acidified ethanol and excellent healing effect of the chronic ulcer induced by acetic acid. The gastroprotective activity in acidified ethanol is partly attributed to the antioxidant mechanisms, while anti-secretory, anti-inflammatory and regeneration of the gastric mucosa are evoked as part of its antiulcer mechanism of action. The gastric ulcer healing of HEPu also involves restoration of the altered cytokines levels to near normal. However, it has no in vitro anti-H. pylori activity. The results of this study showed that HEPu possesses preventive and curative effects in experimental models of gastric ulcers in animals. These effects are partially dependent on antioxidant, antisecretory, anti-inflammatory and mucosa regeneration. It is

Beneficial effects of chronic oxytocin administration and social co-housing in a rodent model of post-traumatic stress disorder.

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Janezic, Eric M; Uppalapati, Swetha; Nagl, Stephanie; Contreras, Marco; French, Edward D; Fellous, Jean-Marc

2016-12-01

Post-traumatic stress disorder (PTSD) is in part due to a deficit in memory consolidation and extinction. Oxytocin (OXT) has anxiolytic effects and promotes prosocial behaviors in both rodents and humans, and evidence suggests that it plays a role in memory consolidation. We studied the effects of administered OXT and social co-housing in a rodent model of PTSD. Acute OXT yielded a short-term increase in the recall of the traumatic memory if administered immediately after trauma. Low doses of OXT delivered chronically had a cumulating anxiolytic effect that became apparent after 4 days and persisted. Repeated injections of OXT after short re-exposures to the trauma apparatus yielded a long-term reduction in anxiety. Co-housing with naive nonshocked animals decreased the memory of the traumatic context compared with single-housed animals. In the long term, these animals showed less thigmotaxis and increased interest in novel objects, and a low OXT plasma level. Co-housed PTSD animals showed an increase in risk-taking behavior. These results suggest beneficial effects of OXT if administered chronically through increases in memory consolidation after re-exposure to a safe trauma context. We also show differences between the benefits of social co-housing with naive rats and co-housing with other shocked animals on trauma-induced long-term anxiety.

Radiation-induced mammary carcinogenesis in rodent models. What's different from chemical carcinogenesis?

International Nuclear Information System (INIS)

Imaoka, Tatsuhiko; Nishimura, Mayumi; Iizuka, Daisuke; Daino, Kazuhiro; Takabatake, Takashi; Okamoto, Mieko; Kakinuma, Shizuko; Shimada, Yoshiya

2009-01-01

Ionizing radiation is one of a few well-characterized etiologic factors of human breast cancer. Laboratory rodents serve as useful experimental models for investigating dose responses and mechanisms of cancer development. Using these models, a lot of information has been accumulated about mammary gland cancer, which can be induced by both chemical carcinogens and radiation. In this review, we first list some experimental rodent models of breast cancer induction. We then focus on several topics that are important in understanding the mechanisms and risk modification of breast cancer development, and compare radiation and chemical carcinogenesis models. We will focus on the pathology and natural history of cancer development in these models, genetic changes observed in induced cancers, indirect effects of carcinogens, and finally risk modification by reproductive factors and age at exposure to the carcinogens. In addition, we summarize the knowledge available on mammary stem/progenitor cells as a potential target of carcinogens. Comparison of chemical and radiation carcinogenesis models on these topics indicates certain similarities, but it also indicates clear differences in several important aspects, such as genetic alterations of induced cancers and modification of susceptibility by age and reproductive factors. Identification of the target cell type and relevant translational research for human risk management may be among the important issues that are addressed by radiation carcinogenesis models. (author)

Kynurenine–3–monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis

Science.gov (United States)

Mole, Damian J; Webster, Scott P; Uings, Iain; Zheng, Xiaozhong; Binnie, Margaret; Wilson, Kris; Hutchinson, Jonathan P; Mirguet, Olivier; Walker, Ann; Beaufils, Benjamin; Ancellin, Nicolas; Trottet, Lionel; Bénéton, Véronique; Mowat, Christopher G; Wilkinson, Martin; Rowland, Paul; Haslam, Carl; McBride, Andrew; Homer, Natalie ZM; Baily, James E; Sharp, Matthew GF; Garden, O James; Hughes, Jeremy; Howie, Sarah EM; Holmes, Duncan S; Liddle, John; Iredale, John P

2015-01-01

Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death1,2 Acute mortality from AP-MODS exceeds 20%3 and for those who survive the initial episode, their lifespan is typically shorter than the general population4. There are no specific therapies available that protect individuals against AP-MODS. Here, we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism5, is central to the pathogenesis of AP-MODS. We created a mouse strain deficient for Kmo with a robust biochemical phenotype that protected against extrapancreatic tissue injury to lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Å resolution. Treatment with GSK180 resulted in rapid changes in levels of kynurenine pathway metabolites in vivo and afforded therapeutic protection against AP-MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS and open up a new area for drug discovery in critical illness. PMID:26752518

Characterization of an acute molecular marker of nongenotoxic rodent hepatocarcinogenesis by gene expression profiling in a long term clofibric acid study.

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Michel, Cécile; Roberts, Ruth A; Desdouets, Chantal; Isaacs, Kevin R; Boitier, Eric

2005-04-01

Evaluation of the nongenotoxic potential early during the development of a drug presents a major challenge. Recently, two genes were identified as potential molecular markers of rodent hepatic carcinogenesis: transforming growth factor-beta stimulated clone 22 (TSC-22) and NAD(P)H cytochrome P450 oxidoreductase (CYP-R) (1). They were identified after comparing the gene expression profiles obtained from the livers of Sprague-Dawley rats treated with different genotoxic and nongenotoxic compounds in a 5 day repeat dose in vivo study. To assess the potential of these two genes as acute markers of carcinogenesis, we investigated their modulation during a long-term nongenotoxic study in the rat using a classic initiation-promotion regime. Clofibric acid (CLO), which belongs to the broad class of chemicals known as peroxisome proliferators, was used as a nongenotoxic hepatocarcinogen. Male F344 rats were given a single nonnecrogenic injection of diethylnitrosamine (0 or 30 mg/kg) and fed a diet containing none or 5000 ppm CLO for up to 20 months. Necropsies of five rats per groups were performed at 18, 46, 102, 264, 377, 447 (control, DEN, and DEN + CLO rats), 524, and 608 days (for the CLO and control rats). Gross macroscopic and microscopic evaluation and gene expression profiling (on Affymetrix microarrays) were performed in peritumoral and tumoral liver tissues. Bioanalysis of the liver gene expression data revealed that TSC-22 was strongly down-regulated early in the study. Its underexpression was maintained throughout the study but disappeared upon CLO withdrawal. These modulations were confirmed by real-time polymerase chain reaction. However, CYP-R gene expression was not significantly altered in our study. Taken together, our results showed that TSC-22, but not CYP-R, has the potential to be an acute early molecular marker for nongenotoxic hepatocarcinogenesis in rodents.

Gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves against acute gastric lesion models in rodents

Directory of Open Access Journals (Sweden)

Hélio B Fernandes

2010-01-01

Full Text Available Parkia platycephala Benth. (Leguminosae - Mimosoideae, popularly known as "visgueira", fava bean tree or "fava-de-bolota", is widely found in the Northern and Northeastern regions of Brazil. Its pods are used as cattle food supplement in the drought period. Compounds with a gastroprotective activity were obtained from the genus Parkia. Therefore, this study aimed at investigating the gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves (Pp-EtOH, as well as evaluating its possible mechanisms of action in experimental ulcer induction models. Lesions were induced by absolute ethanol, ethanol-HCl, ischemia-reperfusion and indomethacin in rodents. Pp-EtOH showed a protective effect in the lesion models (66, 48 and 52 %, respectively, but it was not able to protect gastric mucosa against indomethacin-induced lesions. Results show a possible participation of the NO-synthase pathway in the gastroprotection and an antioxidant activity, by the increase of the catalase activity. The participation of prostaglandins and potassium channels sensitive to ATP in the gastroprotective effect of Pp-EtOH seems less likely to occur. More comprehensive studies, therefore, should be carried out to elucidate the antiulcerative effects of this promising natural product against this gastrointestinal disorder.

Tactile learning in rodents: Neurobiology and neuropharmacology.

Science.gov (United States)

Roohbakhsh, Ali; Shamsizadeh, Ali; Arababadi, Mohammad Kazemi; Ayoobi, Fateme; Fatemi, Iman; Allahtavakoli, Mohammad; Mohammad-Zadeh, Mohammad

2016-02-15

Animal models of learning and memory have been the subject of considerable research. Rodents such as mice and rats are nocturnal animals with poor vision, and their survival depends on their sense of touch. Recent reports have shown that whisker somatosensation is the main channel through which rodents collect and process environmental information. This review describes tactile learning in rodents from a neurobiological and neuropharmacological perspective, and how this is involved in memory-related processes. Copyright © 2016 Elsevier Inc. All rights reserved.

Optical imaging of oxidative stress in retinitis pigmentosa (RP) in rodent model

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Ghanian, Zahra; Maleki, Sepideh; Gopalakrishnan, Sandeep; Sepehr, Reyhaneh; Eells, Janis T.; Ranji, Mahsa

2013-02-01

Oxidative stress (OS), which increases during retinal degenerative disorders, contributes to photoreceptor cell loss. The objective of this study was to investigate the changes in the metabolic state of the eye tissue in rodent models of retinitis pigmentosa by using the cryofluorescence imaging technique. The mitochondrial metabolic coenzymes NADH and FADH2 are autofluorescent and can be monitored without exogenous labels using optical techniques. The NADH redox ratio (RR), which is the ratio of the fluorescence intensity of these fluorophores (NADH/FAD), was used as a quantitative diagnostic marker. The NADH RR was examined in an established rodent model of retinitis pigmentosa (RP), the P23H rat, and compared to that of control Sprague-Dawley (SD) rats and P23H NIR treated rats. Our results demonstrated 24% decrease in the mean NADH RR of the eyes from P23H transgenic rats compared to normal rats and 20% increase in the mean NADH RR of the eyes from the P23H NIR treated rats compared to P23H non-treated rats.

From the Rodent Spinal Cord Injury Model to Human Application: Promises and Challenges.

Science.gov (United States)

Dietz, Volker; Schwab, Martin E

2017-05-01

Repair of the spinal cord and improvement of mobility after injury has been a matter of basic and clinical research for several decades. A number of repair approaches were performed in animals, mainly rodent models of spinal cord injury (SCI). Some of these experimental therapies resulted in significant regeneration of tract fibers, formation of new connections and circuits, and associated improvement of mobility. Some clinical trials aiming at translating these approaches to the human condition of an SCI are currently on-going. The present therapy, however, remains rehabiliation: Mobility of patients with an SCI can be improved to a limited extent by the exploition of neuroplasticity. In this article the present state of the art in the field of SCI research will be discussed. Studies dealing with the promotion of spinal cord repair and those directed to improve mobility by exploition of neuroplasticity will be summarized. The promises and challenges of translational basic research in rodent SCI models will be presented.

Use of rodents as models of human diseases

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Thierry F Vandamme

2014-01-01

Full Text Available Advances in molecular biology have significantly increased the understanding of the biology of different diseases. However, these discoveries have not yet been fully translated into improved treatments for patients with diseases such as cancers. One of the factors limiting the translation of knowledge from preclinical studies to the clinic has been the limitations of in vivo diseases models. In this brief review, we will discuss the advantages and disadvantages of rodent models that have been developed to simulate human pathologies, focusing in models that employ xenografts and genetic modification. Within the framework of genetically engineered mouse (GEM models, we will review some of the current genetic strategies for modeling diseases in the mouse and the preclinical studies that have already been undertaken. We will also discuss how recent improvements in imaging technologies may increase the information derived from using these GEMs during early assessments of potential therapeutic pathways. Furthermore, it is interesting to note that one of the values of using a mouse model is the very rapid turnover rate of the animal, going through the process of birth to death in a very short timeframe relative to that of larger mammalian species.

The bioeconomics of controlling an African rodent pest species

DEFF Research Database (Denmark)

Skonhoft, Anders; Leirs, Herwig; Andreassen, Harry P

2006-01-01

The paper treats the economy of controlling an African pest rodent, the multimammate rat, causing major damage in maize production. An ecological population model is presented and used as a basis for the economic analyses carried out at the village level using data from Tanzania. This model...... incorporates both density-dependent and density-independent (stochastic) factors. Rodents are controlled by applying poison, and the costs are made up of the cost of poison plus the damage to maize production. We analyse how the present-value costs of maize production are affected by various rodent control...

Urban resident attitudes toward rodents, rodent control products, and environmental effects

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Rodent control in urban areas can result in the inadvertent mortality of non-target species (e.g., bobcats). However, there is little detailed information about rodent control practices of urban residents. Our objective was to evaluate urban rodent control behaviors in two area...

Arvicanthis ansorgei, a Novel Model for the Study of Sleep and Waking in Diurnal Rodents

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Hubbard, Jeffrey; Ruppert, Elisabeth; Calvel, Laurent; Robin-Choteau, Ludivine; Gropp, Claire-Marie; Allemann, Caroline; Reibel, Sophie; Sage-Ciocca, Dominique; Bourgin, Patrice

2015-01-01

Study Objectives: Sleep neurobiology studies use nocturnal species, mainly rats and mice. However, because their daily sleep/wake organization is inverted as compared to humans, a diurnal model for sleep studies is needed. To fill this gap, we phenotyped sleep and waking in Arvicanthis ansorgei, a diurnal rodent widely used for the study of circadian rhythms. Design: Video-electroencephalogram (EEG), electromyogram (EMG), and electrooculogram (EOG) recordings. Setting: Rodent sleep laboratory. Participants: Fourteen male Arvicanthis ansorgei, aged 3 mo. Interventions: 12 h light (L):12 h dark (D) baseline condition, 24-h constant darkness, 6-h sleep deprivation. Measurements and Results: Wake and rapid eye movement (REM) sleep showed similar electrophysiological characteristics as nocturnal rodents. On average, animals spent 12.9 h ± 0.4 awake per 24-h cycle, of which 6.88 h ± 0.3 was during the light period. NREM sleep accounted for 9.63 h ± 0.4, which of 5.13 h ± 0.2 during dark period, and REM sleep for 89.9 min ± 6.7, which of 52.8 min ± 4.4 during dark period. The time-course of sleep and waking across the 12 h light:12 h dark was overall inverted to that observed in rats or mice, though with larger amounts of crepuscular activity at light and dark transitions. A dominant crepuscular regulation of sleep and waking persisted under constant darkness, showing the lack of a strong circadian drive in the absence of clock reinforcement by external cues, such as a running wheel. Conservation of the homeostatic regulation was confirmed with the observation of higher delta power following sustained waking periods and a 6-h sleep deprivation, with subsequent decrease during recovery sleep. Conclusions: Arvicanthis ansorgei is a valid diurnal rodent model for studying the regulatory mechanisms of sleep and so represents a valuable tool for further understanding the nocturnality/diurnality switch. Citation: Hubbard J, Ruppert E, Calvel L, Robin-Choteau L, Gropp CM

Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

International Nuclear Information System (INIS)

Valerio, Luis G.; Arvidson, Kirk B.; Chanderbhan, Ronald F.; Contrera, Joseph F.

2007-01-01

Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest is MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals

Comparison of blood biochemics between acute myocardial infarction models with blood stasis and simple acute myocardial infarction models in rats

International Nuclear Information System (INIS)

Qu Shaochun; Yu Xiaofeng; Wang Jia; Zhou Jinying; Xie Haolin; Sui Dayun

2010-01-01

Objective: To construct the acute myocardial infarction models in rats with blood stasis and study the difference on blood biochemics between the acute myocardial infarction models with blood stasis and the simple acute myocardial infarction models. Methods: Wistar rats were randomly divided into control group, acute blood stasis model group, acute myocardial infarction sham operation group, acute myocardial infarction model group and of acute myocardial infarction model with blood stasis group. The acute myocardial infarction models under the status of the acute blood stasis in rats were set up. The serum malondialdehyde (MDA), nitric oxide (NO), free fatty acid (FFA), tumor necrosis factor-α (TNF-α) levels were detected, the activities of serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the levels of prostacycline (PGI2), thromboxane A 2 (TXA 2 ) and endothelin (ET) in plasma were determined. Results: There were not obvious differences in MDA, SOD, GSH-Px and FFA between the acute myocardial infarction models with blood stasis in rats and the simple acute myocardial infarction models (P 2 and NO, and the increase extents of TXA 2 , ET and TNF-α in the acute myocardial infarction models in rats with blood stasis were higher than those in the simple acute myocardial infarction models (P 2 and NO, are significant when the acute myocardial infarction models in rats with blood stasis and the simple acute myocardial infarction models are compared. The results show that it is defective to evaluate pharmacodynamics of traditional Chinese drug with only simple acute myocardial infarction models. (authors)

Examination of Gelatinase Isoforms in Rodent Models of Acute Neurodegenerative Diseases Using Two-Dimensional Zymography.

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Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Qu, Zhe; Cui, Jiankun; Gu, Zezong

2017-01-01

Pathological activation of gelatinases (matrix metalloproteinase-2 and -9; MMP-2/-9) has been shown to cause a number of detrimental outcomes in neurodegenerative diseases. In gel gelatin zymography is a highly sensitive methodology commonly used in revealing levels of gelatinase activity and in separating the proform and active form of gelatinases, based on their different molecular weights. However, this methodology is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity can be regulated at transcriptional and/or post-translational levels under in vivo conditions resulting in alternation of their isoelectric focusing (IEF) points. In this chapter, we describe an advanced methodology, termed two-dimensional zymography, combining IEF with zymographic electrophoresis under non-reducing conditions to achieve significant improvement in separation of the gelatinase isoforms in both cell-based and in vivo models for acute brain injuries and neuroinflammation.

Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology.

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Wen Liang

Full Text Available The recently developed histological scoring system for non-alcoholic fatty liver disease (NAFLD by the NASH Clinical Research Network (NASH-CRN has been widely used in clinical settings, but is increasingly employed in preclinical research as well. However, it has not been systematically analyzed whether the human scoring system can directly be converted to preclinical rodent models. To analyze this, we systematically compared human NAFLD liver pathology, using human liver biopsies, with liver pathology of several NAFLD mouse models. Based upon the features pertaining to mouse NAFLD, we aimed at establishing a modified generic scoring system that is applicable to broad spectrum of rodent models.The histopathology of NAFLD was analyzed in several different mouse models of NAFLD to define generic criteria for histological assessment (preclinical scoring system. For validation of this scoring system, 36 slides of mouse livers, covering the whole spectrum of NAFLD, were blindly analyzed by ten observers. Additionally, the livers were blindly scored by one observer during two separate assessments longer than 3 months apart.The criteria macrovesicular steatosis, microvesicular steatosis, hepatocellular hypertrophy, inflammation and fibrosis were generally applicable to rodent NAFLD. The inter-observer reproducibility (evaluated using the Intraclass Correlation Coefficient between the ten observers was high for the analysis of macrovesicular steatosis and microvesicular steatosis (ICC = 0.784 and 0.776, all p<0.001, respectively and moderate for the analysis of hypertrophy and inflammation (ICC = 0.685 and 0.650, all p<0.001, respectively. The intra-observer reproducibility between the different observations of one observer was high for the analysis of macrovesicular steatosis, microvesicular steatosis and hypertrophy (ICC = 0.871, 0.871 and 0.896, all p<0.001, respectively and very high for the analysis of inflammation (ICC = 0.931, p

Models and detection of spontaneous recurrent seizures in laboratory rodents

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Bin Gu

2017-07-01

Full Text Available Epilepsy, characterized by spontaneous recurrent seizures (SRS, is a serious and common neurological disorder afflicting an estimated 1% of the population worldwide. Animal experiments, especially those utilizing small laboratory rodents, remain essential to understanding the fundamental mechanisms underlying epilepsy and to prevent, diagnose, and treat this disease. While much attention has been focused on epileptogenesis in animal models of epilepsy, there is little discussion on SRS, the hallmark of epilepsy. This is in part due to the technical difficulties of rigorous SRS detection. In this review, we comprehensively summarize both genetic and acquired models of SRS and discuss the methodology used to monitor and detect SRS in mice and rats.

Osseointegration of biochemically modified implants in an osteoporosis rodent model

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B Stadlinger

2013-07-01

Full Text Available The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX osteoporotic rats (n = 32/group. In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout. Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC, peri-implant bone area (BA, bone volume/tissue volume (BV/TV and bone-mineral density (BMD in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

Template based rodent brain extraction and atlas mapping.

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Weimin Huang; Jiaqi Zhang; Zhiping Lin; Su Huang; Yuping Duan; Zhongkang Lu

2016-08-01

Accurate rodent brain extraction is the basic step for many translational studies using MR imaging. This paper presents a template based approach with multi-expert refinement to automatic rodent brain extraction. We first build the brain appearance model based on the learning exemplars. Together with the template matching, we encode the rodent brain position into the search space to reliably locate the rodent brain and estimate the rough segmentation. With the initial mask, a level-set segmentation and a mask-based template learning are implemented further to the brain region. The multi-expert fusion is used to generate a new mask. We finally combine the region growing based on the histogram distribution learning to delineate the final brain mask. A high-resolution rodent atlas is used to illustrate that the segmented low resolution anatomic image can be well mapped to the atlas. Tested on a public data set, all brains are located reliably and we achieve the mean Jaccard similarity score at 94.99% for brain segmentation, which is a statistically significant improvement compared to two other rodent brain extraction methods.

Barriers to developing a valid rodent model of Alzheimer's disease: from behavioural analysis to etiologicalmechanisms

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Darryl Christopher Gidyk

2015-07-01

Full Text Available Sporadic Alzheimer's disease is the most prevalent form of age-related dementia. As such, great effort has been put forth to investigate the etiology, progression, and underlying mechanisms of the disease. Countless studies have been conducted however the details of this disease remain largely unknown. Rodent models provide opportunities to investigate certain aspects of AD that cannot be ethically studied in humans. These animal models vary from study to study and have provided some insight, but no real advancements in the prevention or treatment of the disease. In this Hypothesis and Theory paper, we discuss what we perceive as barriers to impactful discovery in rodent AD research and we offer solutions for moving forward. Although no single model of AD is capable of providing the solution to the growing epidemic of the disease, we encourage a comprehensive approach that acknowledges the complex etiology of AD with the goal of enhancing the bidirectional translatability from bench to bedside and vice versa.

Ghrelin influences novelty seeking behavior in rodents and men.

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Hansson, Caroline; Shirazi, Rozita H; Näslund, Jakob; Vogel, Heike; Neuber, Corinna; Holm, Göran; Anckarsäter, Henrik; Dickson, Suzanne L; Eriksson, Elias; Skibicka, Karolina P

2012-01-01

Recent discoveries indicate an important role for ghrelin in drug and alcohol reward and an ability of ghrelin to regulate mesolimbic dopamine activity. The role of dopamine in novelty seeking, and the association between this trait and drug and alcohol abuse, led us to hypothesize that ghrelin may influence novelty seeking behavior. To test this possibility we applied several complementary rodent models of novelty seeking behavior, i.e. inescapable novelty-induced locomotor activity (NILA), novelty-induced place preference and novel object exploration, in rats subjected to acute ghrelin receptor (growth hormone secretagogue receptor; GHSR) stimulation or blockade. Furthermore we assessed the possible association between polymorphisms in the genes encoding ghrelin and GHSR and novelty seeking behavior in humans. The rodent studies indicate an important role for ghrelin in a wide range of novelty seeking behaviors. Ghrelin-injected rats exhibited a higher preference for a novel environment and increased novel object exploration. Conversely, those with GHSR blockade drastically reduced their preference for a novel environment and displayed decreased NILA. Importantly, the mesolimbic ventral tegmental area selective GHSR blockade was sufficient to reduce the NILA response indicating that the mesolimbic GHSRs might play an important role in the observed novelty responses. Moreover, in untreated animals, a striking positive correlation between NILA and sucrose reward behavior was detected. Two GHSR single nucleotide polymorphisms (SNPs), rs2948694 and rs495225, were significantly associated with the personality trait novelty seeking, as assessed using the Temperament and Character Inventory (TCI), in human subjects. This study provides the first evidence for a role of ghrelin in novelty seeking behavior in animals and humans, and also points to an association between food reward and novelty seeking in rodents.

Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents

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Ayman Goudah

2015-05-01

Full Text Available Aim: The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days in Sprague Dawley rats. Materials and Methods: Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control and 250 mg/kg in Sprague Dawley rats. Results: The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. Conclusion: We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg.

Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents.

Science.gov (United States)

Goudah, Ayman; Abdo-El-Sooud, Khaled; Yousef, Manal A

2015-05-01

The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days) in Sprague Dawley rats. Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control) and 250 mg/kg in Sprague Dawley rats. The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg.

Preventive effects of Flos Perariae (Gehua water extract and its active ingredient puerarin in rodent alcoholism models

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Wang Yuqiang

2010-10-01

Full Text Available Abstract Background Radix Puerariae is used in Chinese medicine to treat alcohol addiction and intoxication. The present study investigates the effects of Flos puerariae lobatae water extract (FPE and its active ingredient puerarin on alcoholism using rodent models. Methods Alcoholic animals were given FPE or puerarin by oral intubation prior or after alcohol treatment. The loss of righting reflex (LORR assay was used to evaluate sedative/hypnotic effects. Changes of gama-aminobutyric acid type A receptor (GABAAR subunits induced by alcohol treatment in hippocampus were measured with western blot. In alcoholic mice, body weight gain was monitored throughout the experiments. Alcohol dehydrogenase (ADH levels in liver were measured. Results FPE and puerarin pretreatment significantly prolonged the time of LORR induced by diazepam in acute alcoholic rat. Puerarin increased expression of gama-aminobutyric acid type A receptor alpha1 subunit and decreased expression of alpha4 subunit. In chronic alcoholic mice, puerarin pretreatment significantly increased body weight and liver ADH activity in a dose-dependent manner. Puerarin pretreatment, but not post-treatment, can reverse the changes of gama-aminobutyric acid type A receptor subunit expression and increase ADH activity in alcoholism models. Conclusion The present study demonstrates that FPE and its active ingredient puerarin have preventive effects on alcoholism related disorders.

Effects of L-arginine on anatomical and electrophysiological deterioration of the eye in a rodent model of nonarteritic ischemic optic neuropathy.

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Chuman, Hideki; Maekubo, Tomoyuki; Osako, Takako; Ishiai, Michitaka; Kawano, Naoko; Nao-I, Nobuhisa

2013-07-01

The aims of this study were to clarify the effectiveness of L-arginine (1) for reducing the severity of anatomical changes in the eye and improving visual function in the acute stage of a rodent model of nonarteritic ischemic optic neuropathy (rNAION) and (2) in preventing those changes in anatomy and visual function. For the first aim, L-arginine was intravenously injected into rats 3 h after rNAION induction; for the second aim, rNAION was induced after the oral administration of L-arginine for 7 days. The inner retinal thickness was determined over time by optical coherence tomography, and the amplitude of the scotopic threshold response (STR) and the number of surviving retinal ganglion cells (RGCs) were measured. These data were compared with the baseline data from the control group. Both intravenous infusion of L-arginine after rNAION induction and oral pretreatment with L-arginine significantly decreased optic disc edema in the acute stage and thinning of the inner retina, reduced the decrease in STR amplitude, and reduced the decrease in the number of RGCs during rNAION. Based on these results, we conclude that L-arginine treatment is effective for reducing anatomical changes in the eye and improving visual function in the acute stage of rNAION and that pretreatment with L-arginine is an effective therapy to reduce the severity of the condition during recurrence in the other eye.

MR microscopy of the lung in small rodents

International Nuclear Information System (INIS)

Takahashi, Masaya; Kubo, Shigeto; Kiryu, Shigeru; Gee, James; Hatabu, Hiroto

2007-01-01

Understanding how the mammalian respiratory system works and how it changes in disease states and under the influence of drugs is frequently pursued in model systems such as small rodents. These have many advantages, including being easily obtained in large numbers as purebred strains. Studies in small rodents are valuable for proof of concept studies and for increasing our knowledge about disease mechanisms. Since the recent developments in the generation of genetically designed animal models of disease, one needs the ability to assess morphology and function in in vivo systems. In this article, we first review previous reports regarding thoracic imaging. We then discuss approaches to take in making use of small rodents to increase MR microscopic sensitivity for these studies and to establish MR methods for clinically relevant lung imaging

The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis.

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Pung, Yuh Fen; Chilian, William M; Bennett, Martin R; Figg, Nichola; Kamarulzaman, Mohd Hamzah

2017-03-01

Although there are multiple rodent models of the metabolic syndrome, very few develop vascular complications. In contrast, the JCR:LA-cp rat develops both metabolic syndrome and early atherosclerosis in predisposed areas. However, the pathology of the normal vessel wall has not been described. We examined JCR:LA control (+/+) or cp/cp rats fed normal chow diet for 6 or 18 mo. JCR:LA-cp rats developed multiple features of advanced cystic medial necrosis including "cysts," increased collagen formation and proteoglycan deposition around cysts, apoptosis of vascular smooth muscle cells, and spotty medial calcification. These appearances began within 6 mo and were extensive by 18 mo. JCR:LA-cp rats had reduced medial cellularity, increased medial thickness, and vessel hypoxia that was most marked in the adventitia. In conclusion, the normal chow-fed JCR:LA-cp rat represents a novel rodent model of cystic medial necrosis, associated with multiple metabolic abnormalities, vascular smooth muscle cell apoptosis, and vessel hypoxia. NEW & NOTEWORTHY Triggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN. Copyright © 2017 the American Physiological Society.

Mechanical Elongation of the Small Intestine: Evaluation of Techniques for Optimal Screw Placement in a Rodent Model

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P. A. Hausbrandt

2013-01-01

Full Text Available Introduction. The aim of this study was to evaluate techniques and establish an optimal method for mechanical elongation of small intestine (MESI using screws in a rodent model in order to develop a potential therapy for short bowel syndrome (SBS. Material and Methods. Adult female Sprague Dawley rats (n=24 with body weight from 250 to 300 g (Σ=283 were evaluated using 5 different groups in which the basic denominator for the technique involved the fixation of a blind loop of the intestine on the abdominal wall with the placement of a screw in the lumen secured to the abdominal wall. Results. In all groups with accessible screws, the rodents removed the implants despite the use of washers or suits to prevent removal. Subcutaneous placement of the screw combined with antibiotic treatment and dietary modifications was finally successful. In two animals autologous transplantation of the lengthened intestinal segment was successful. Discussion. While the rodent model may provide useful basic information on mechanical intestinal lengthening, further investigations should be performed in larger animals to make use of the translational nature of MESI in human SBS treatment.

Clinical correlates to assist with chronic traumatic encephalopathy diagnosis: Insights from a novel rodent repeat concussion model.

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Thomsen, Gretchen M; Ko, Ara; Harada, Megan Y; Ma, Annie; Wyss, Livia; Haro, Patricia; Vit, Jean-Philippe; Avalos, Pablo; Dhillon, Navpreet K; Cho, Noell; Shelest, Oksana; Ley, Eric J

2017-06-01

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. Using a rat model of recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. Bilateral, closed-skull, mild TBI was administered once per week to 35 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as "mild" or "severe" and further separated into "acute," "short," and "long" based on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy, phosphorylated tau, and inflammation were assessed. All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, phosphorylated tau, and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology, and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum. Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis.

Social defeat models in animal science: What we have learned from rodent models.

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Toyoda, Atsushi

2017-07-01

Studies on stress and its impacts on animals are very important in many fields of science, including animal science, because various stresses influence animal production and animal welfare. In particular, the social stresses within animal groups have profound impact on animals, with the potential to induce abnormal behaviors and health problems. In humans, social stress induces several health problems, including psychiatric disorders. In animal stress models, social defeat models are well characterized and used in various research fields, particularly in studies concerning mental disorders. Recently, we have focused on behavior, nutrition and metabolism in rodent models of social defeat to elucidate how social stresses affect animals. In this review, recent significant progress in studies related to animal social defeat models are described. In the field of animal science, these stress models may contribute to advances in the development of functional foods and in the management of animal welfare. © 2017 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses.

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Low, Lucie A; Bauer, Lucy C; Pitcher, Mark H; Bushnell, M Catherine

2016-08-01

With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the "nociceptive" central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli.

The bioeconomics of controlling an African rodent pest species

OpenAIRE

Skonhoft, Anders; Herwig, Leirs; Andreassen, Harry Peter; Mulungu, Loth S. A.; Stenseth, Nils Christian

2006-01-01

The paper treats the economy of controlling an African pest rodent, the multimammate rat, causing major damage in maize production. An ecological population model is presented and used as a basis for the economic analyses carried out at the village level using data from Tanzania. This model incorporates both density-dependent and density-independent (stochastic) factors. Rodents are controlled by applying poison, and the economic benefits depend on the income from maize production minus the c...

The Revised Neurobehavioral Severity Scale (NSS-R) for Rodents.

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Yarnell, Angela M; Barry, Erin S; Mountney, Andrea; Shear, Deborah; Tortella, Frank; Grunberg, Neil E

2016-04-08

Motor and sensory deficits are common following traumatic brain injury (TBI). Although rodent models provide valuable insight into the biological and functional outcomes of TBI, the success of translational research is critically dependent upon proper selection of sensitive, reliable, and reproducible assessments. Published literature includes various observational scales designed to evaluate post-injury functionality; however, the heterogeneity in TBI location, severity, and symptomology can complicate behavioral assessments. The importance of choosing behavioral outcomes that can be reliably and objectively quantified in an efficient manner is becoming increasingly important. The Revised Neurobehavioral Severity Scale (NSS-R) is a continuous series of specific, sensitive, and standardized observational tests that evaluate balance, motor coordination, and sensorimotor reflexes in rodents. The tasks follow a specific order designed to minimize interference: balance, landing, tail raise, dragging, righting reflex, ear reflex, eye reflex, sound reflex, tail pinch, and hindpaw pinch. The NSS-R has proven to be a reliable method differentiating brain-injured rodents from non-brain-injured rodents across many brain injury models. Copyright © 2016 John Wiley & Sons, Inc.

Optical imaging of mitochondrial redox state in rodent model of retinitis pigmentosa

Science.gov (United States)

Maleki, Sepideh; Gopalakrishnan, Sandeep; Ghanian, Zahra; Sepehr, Reyhaneh; Schmitt, Heather; Eells, Janis; Ranji, Mahsa

2013-01-01

Oxidative stress (OS) and mitochondrial dysfunction contribute to photoreceptor cell loss in retinal degenerative disorders. The metabolic state of the retina in a rodent model of retinitis pigmentosa (RP) was investigated using a cryo-fluorescence imaging technique. The mitochondrial metabolic coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are autofluorescent and can be monitored without exogenous labels using optical techniques. The cryo-fluorescence redox imaging technique provides a quantitative assessment of the metabolism. More specifically, the ratio of the fluorescence intensity of these fluorophores (NADH/FAD), the NADH redox ratio (RR), is a marker of the metabolic state of the tissue. The NADH RR and retinal function were examined in an established rodent model of RP, the P23H rat compared to that of nondystrophic Sprague-Dawley (SD) rats. The NADH RR mean values were 1.11±0.03 in the SD normal and 0.841±0.01 in the P23H retina, indicating increased OS in the P23H retina. Electroretinographic data revealed a significant reduction in photoreceptor function in P23H animals compared to SD nozrmal rats. Thus, cryo-fluorescence redox imaging was used as a quantitative marker of OS in eyes from transgenic rats and demonstrated that alterations in the oxidative state of eyes occur during the early stages of RP.

Traumatic brain injury–Modeling neuropsychiatric symptoms in rodents

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Oz eMalkesman

2013-10-01

Full Text Available Each year in the United States, approximately 1.5 million people sustain a traumatic brain injury (TBI. Victims of TBI can suffer from chronic post-TBI symptoms, such as sensory and motor deficits, cognitive impairments including problems with memory, learning, and attention, and neuropsychiatric symptoms such as depression, anxiety, irritability, aggression, and suicidal rumination. Although partially associated with the site and severity of injury, the biological mechanisms associated with many of these symptoms—and why some patients experience differing assortments of persistent maladies—are largely unknown. The use of animal models is a promising strategy for elucidation of the mechanisms of impairment and treatment, and learning, memory, sensory and motor tests have widespread utility in rodent models of TBI and psychopharmacology. Comparatively, behavioral tests for the evaluation of neuropsychiatric symptomatology are rarely employed in animal models of TBI and, as determined in this review, the results have been inconsistent. Animal behavioral studies contribute to the understanding of the biological mechanisms by which TBI is associated with neurobehavioral symptoms and offer a powerful means for pre-clinical treatment validation. Therefore, further exploration of the utility of animal behavioral tests for the study of injury mechanisms and therapeutic strategies for the alleviation of emotional symptoms are relevant and essential.

Functional characterization and expression of thalamic GABA(B) receptors in a rodent model of Parkinson's disease

NARCIS (Netherlands)

de Groote, C; Wullner, U; Loschmann, PA; Luiten, PGM; Klockgether, T

1999-01-01

Increased GABAergic neurotransmission of the basal ganglia output nuclei projecting to the motor thalamus is thought to contribute to the pathophysiology of Parkinson's disease. We investigated the functional role of thalamic GABA(B) receptors in a rodent model of Parkinson's disease. First, we

Long-lived cancer-resistant rodents as new model species for cancer research

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Jorge eAzpurua

2013-01-01

Full Text Available Most rodents are small and short-lived, but several lineages have independently evolved long lifespans without a concomitant increase in body mass. Most notably, the two subterranean species naked mole rat (NMR and blind mole rat (BMR which have maximum lifespans of 32 and 21 years respectively. The longevity of these species has sparked interest in the tumor suppression strategies that may have also evolved, because for many rodent species (including mice, rats, guinea pigs, gerbils and hamsters tumors are major source of late-life mortality. Here, we review the recent literature on anticancer mechanisms in long-lived rodents. Both NMR and BMR seem to have developed tumor defenses that rely on extra-cellular signals. However, while the NMR relies on a form of contact inhibition to suppress growth, the BMR evolved a mechanism mediated by the release of interferon and rapid necrotic cell death. Although both organisms ultimately rely on canonical downstream tumor suppressors (pRB and p53 the studies reveal species can evolve different strategies to achieve tumor-resistance. Importantly, studies of these cancer-resistant rodents may benefit human health if such mechanisms can be activated in human cells.

Anti-Inflammatory Effect of Emblica officinalis in Rodent Models of Acute and Chronic Inflammation: Involvement of Possible Mechanisms

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Mahaveer Golechha

2014-01-01

Full Text Available Emblica officinalis, commonly known as amla in Ayurveda, is unarguably the most important medicinal plant for prevention and treatment of various ailments. The present study investigated the anti-inflammatory activity of hydroalcoholic extract of Emblica officinalis (HAEEO. Acute inflammation in rats was induced by the subplantar injection of carrageenan, histamine, serotonin, and prostaglandin E2 and chronic inflammation was induced by the cotton pellet granuloma. Intraperitoneal (i.p. administration of HAEEO at all the tested doses (300, 500, and 700 mg/kg significantly (P<0.001 inhibited rat paw edema against all phlogistic agents and also reduced granuloma formation. However, at the dose of 700 mg/kg, HAEEO exhibited maximum anti-inflammatory activity in all experimental models, and the effects were comparable to that of the standard anti-inflammatory drugs. Additionally, in paw tissue the antioxidant activity of HAEEO was also measured and it was found that HAEEO significantly (P<0.001 increased glutathione, superoxide dismutase, and catalase activity and subsequently reduced lipid peroxidation evidenced by reduced malondialdehyde. Taken all together, the results indicated that HAEEO possessed potent anti-inflammatory activity and it may hold therapeutic promise in the management of acute and chronic inflammatory conditions.

Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

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Menk M

2018-05-01

Full Text Available Mario Menk, Jan Adriaan Graw, Clarissa von Haefen, Hendrik Steinkraus, Burkhard Lachmann, Claudia D Spies, David Schwaiberger Department of Anesthesiology and Operative Intensive Care Medicine, Charité – University Medicine Berlin, FreieUniversität Berlin, Humboldt-Universitätzu Berlin, and Berlin Institute of Health, Germany Purpose: Although the role of the angiotensin II type 2 (AT2 receptor in acute lung injury is not yet completely understood, a protective role of this receptor subtype has been suggested. We hypothesized that, in a rodent model of acute lung injury, stimulation of the AT2 receptor with the direct agonist Compound 21 (C21 might have a beneficial effect on pulmonary inflammation and might improve pulmonary gas exchange. Materials and methods: Male adult rats were divided into a treatment group that received pulmonary lavage followed by mechanical ventilation (LAV, n=9, a group receiving pulmonary lavage, mechanical ventilation, and direct stimulation of the AT2 receptor with C21 (LAV+C21, n=9, and a control group that received mechanical ventilation only (control, n=9. Arterial blood gas analysis was performed every 30 min throughout the 240-min observation period. Lung tissue and plasma samples were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid were assessed and the wet/dry-weight ratio of lungs was determined. Transcriptional and translational regulation of pro- and antiinflammatory cytokines IL-1β, tumor necrosis factor-alpha, IL-6, IL-10, and IL-4 was determined in lungs and in plasma. Results: Pulmonary lavage led to a significant impairment of gas exchange, the formation of lung edema, and the induction of pulmonary inflammation. Protein content of lavage fluid was increased and contained washed-out surfactant. Direct AT2 receptor stimulation with C21 led to a significant inhibition of tumor necrosis factor-alpha and IL-6

In vivo efficacy of acyl CoA: diacylglycerol acyltransferase (DGAT) 1 inhibition in rodent models of postprandial hyperlipidemia.

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King, Andrew J; Segreti, Jason A; Larson, Kelly J; Souers, Andrew J; Kym, Philip R; Reilly, Regina M; Collins, Christine A; Voorbach, Martin J; Zhao, Gang; Mittelstadt, Scott W; Cox, Bryan F

2010-07-10

Postprandial serum triglyceride concentrations have recently been identified as a major, independent risk factor for future cardiovascular events. As a result, postprandial hyperlipidemia has emerged as a potential therapeutic target. The purpose of this study was two-fold. Firstly, to describe and characterize a standardized model of postprandial hyperlipidemia in multiple rodent species; and secondly, apply these rodent models to the evaluation of a novel class of pharmacologic agent; acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitors. Serum triglycerides were measured before and for 4h after oral administration of a standardized volume of corn oil, to fasted C57BL/6, ob/ob, apoE(-/-) and CD-1 mice; Sprague-Dawley and JCR/LA-cp rats; and normolipidemic and hyperlipidemic hamsters. Intragastric administration of corn oil increased serum triglycerides in all animals evaluated, however the magnitude and time-course of the postprandial triglyceride excursion varied. The potent and selective DGAT-1 inhibitor A-922500 (0.03, 0.3 and 3 mg/kg, p.o.), dose-dependently attenuated the maximal postprandial rise in serum triglyceride concentrations in all species tested. At the highest dose of DGAT-1 inhibitor, the postprandial triglyceride response was abolished. This study provides a comprehensive characterization of the time-course of postprandial hyperlipidemia in rodents. In addition, the ability of DGAT-1 inhibitors to attenuate postprandial hyperlipidemia in multiple rodent models, including those that feature insulin resistance, is documented. Exaggerated postprandial hyperlipidemia is inherent to insulin-resistant states in humans and contributes to the substantially elevated cardiovascular risk observed in these patients. Therefore, by attenuating postprandial hyperlipidemia, DGAT-1 inhibition may represent a novel therapeutic approach to reduce cardiovascular risk. Copyright 2010 Elsevier B.V. All rights reserved.

[Biological and neural bases of partner preferences in rodents: models to understand human pair bonds].

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Coria-Avila, G A; Hernández-Aguilar, M E; Toledo-Cárdenas, R; García-Hernández, L I; Manzo, J; Pacheco, P; Miquel, M; Pfaus, J G

To analyse the biological and neural bases of partner preference formation in rodents as models to understand human pair bonding. Rodents are social individuals, capable of forming short- or long-lasting partner preferences that develop slowly by stimuli like cohabitation, or rapidly by stimuli like sex and stress. Dopamine, corticosteroids, oxytocin, vasopressin, and opioids form the neurochemical substrate for pair bonding in areas like the nucleus accumbens, the prefrontal cortex, the piriform cortex, the medial preoptic area, the ventral tegmental area and the medial amygdala, among others. Additional areas may participate depending on the nature of the conditioned stimuli by which and individual recognizes a preferred partner. Animal models help us understand that the capacity of an individual to display long-lasting and selective preferences depends on neural bases, selected throughout evolution. The challenge in neuroscience is to use this knowledge to create new solutions for mental problems associated with the incapacity of an individual to display a social bond, keep one, or cope with the disruption of a consolidated one.

The in vivo rodent test systems for assessment of carcinogenic potential

DEFF Research Database (Denmark)

van der Laan, Jan-Willem; Spindler, Per

2002-01-01

A Drug Information Association (DIA) workshop was held in May 2001 to discuss the outcome of the International Life Sciences Institute-Health and Environmental Sciences Institute (ILSI-HESI) project on alternative models for carcinogenicity assessment such as the P53(+/-) and XPA(+/-) knockout...... mouse models, the RasH2 and Tg.AC transgenic mouse models, and the neonatal mouse model. The "ICH Guideline S1B on Testing for Carcinogenicity of Pharmaceuticals" advocates that carcinogenicity testing of pharmaceuticals, when needed, might be carried out choosing one 2-year rodent carcinogenicity study...... (rat) plus one other study that supplements the 2-year study and providing additional information that is not readily available from the 2-year study: either (1) a short- or medium-term in vivo rodent test system or (2) a 2-year carcinogenicity study in a second rodent species (mouse). Another topic...

Modelling the emergence of rodent filial huddling from physiological huddling

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Wilson, Stuart P.

2017-11-01

Huddling behaviour in neonatal rodents reduces the metabolic costs of physiological thermoregulation. However, animals continue to huddle into adulthood, at ambient temperatures where they are able to sustain a basal metabolism in isolation from the huddle. This `filial huddling' in older animals is known to be guided by olfactory rather than thermal cues. The present study aimed to test whether thermally rewarding contacts between young mice, experienced when thermogenesis in brown adipose fat tissue (BAT) is highest, could give rise to olfactory preferences that persist as filial huddling interactions in adults. To this end, a simple model was constructed to fit existing data on the development of mouse thermal physiology and behaviour. The form of the model that emerged yields a remarkable explanation for filial huddling; associative learning maintains huddling into adulthood via processes that reduce thermodynamic entropy from BAT metabolism and increase information about social ordering among littermates.

Relationships between rodent white adipose fat pads and human white adipose fat depots

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Daniella E. Chusyd

2016-04-01

Full Text Available The objective of this review was to compare and contrast the physiological and metabolic profiles of rodent white adipose fat pads with white adipose fat depots in humans. Human fat distribution and its metabolic consequences have received extensive attention, but much of what has been tested in translational research has relied heavily on rodents. Unfortunately, the validity of using rodent fat pads as a model of human adiposity has received less attention. There is a surprisingly lack of studies demonstrating an analogous relationship between rodent and human adiposity on obesity-related comorbidities. Therefore, we aimed to compare known similarities and disparities in terms of white adipose tissue development and distribution, sexual dimorphism, weight loss, adipokine secretion, and aging. While the literature supports the notion that many similarities exist between rodents and humans, notable differences emerge related to fat deposition and function of white adipose tissue. Thus, further research is warranted to more carefully define the strengths and limitations of rodent white adipose tissue as a model for humans, with a particular emphasis on comparable fat depots, such as mesenteric fat.

Evidence of human hantavirus infection and zoonotic investigation of hantavirus prevalence in rodents in western Java, Indonesia.

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Kosasih, Herman; Ibrahim, Ima Nurisa; Wicaksana, Rudi; Alisjahbana, Bachti; Hoo, Yumilia; Yo, Iing H; Antonjaya, Ungke; Widjaja, Susana; Winoto, Imelda; Williams, Maya; Blair, Patrick J

2011-06-01

During febrile surveillance in the western Java City of Bandung, Indonesia, a patient with clinical symptoms consistent with hantavirus infection was found to have elevated titers of hantavirus-specific immunoglobulin M (IgM) and IgG antibodies. A subsequent epizoological investigation demonstrated a higher prevalence of hantavirus IgG antibodies in rodents trapped in the vicinity of the patient's home compared with rodents from a control area (13.2% vs. 4.7%, p = 0.036). The Old World Seoul hantavirus was detected by reverse transcriptase-polymerase chain reaction in the organs of 71% of the seropositive rodents tested. This is the first report of a Seoul virus infection in Indonesia supported by clinical, serological, and epizoological evidences. These findings suggest that hantavirus infection should be on the clinical differential diagnosis when acutely ill febrile patients report for care in western Java.

Mathematical methods to model rodent behavior in the elevated plus-maze.

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Arantes, Rafael; Tejada, Julián; Bosco, Geraldine G; Morato, Silvio; Roque, Antonio C

2013-11-15

The elevated plus maze is a widely used experimental test to study anxiety-like rodent behavior. It is made of four arms, two open and two closed, connected at a central area forming a plus shaped maze. The whole apparatus is elevated 50 cm from the floor. The anxiety of the animal is usually assessed by the number of entries and duration of stay in each arm type during a 5-min period. Different mathematical methods have been proposed to model the mechanisms that control the animal behavior in the maze, such as factor analysis, statistical inference on Markov chains and computational modeling. In this review we discuss these methods and propose possible extensions of them as a direction for future research. Copyright © 2013 Elsevier B.V. All rights reserved.

Transplacental Nutrient Transport Mechanisms of Intrauterine Growth Restriction in Rodent Models and Humans.

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Winterhager, Elke; Gellhaus, Alexandra

2017-01-01

Although the causes of intrauterine growth restriction (IUGR) have been intensively investigated, important information is still lacking about the role of the placenta as a link from adverse maternal environment to adverse pregnancy outcomes of IUGR and preterm birth. IUGR is associated with an increased risk of cardiovascular, metabolic, and neurological diseases later in life. Determination of the most important pathways that regulate transplacental transport systems is necessary for identifying marker genes as diagnostic tools and for developing drugs that target the molecular pathways. Besides oxygen, the main nutrients required for appropriate fetal development and growth are glucose, amino acids, and fatty acids. Dysfunction in transplacental transport is caused by impairments in both placental morphology and blood flow, as well as by factors such as alterations in the expression of insulin-like growth factors and changes in the mTOR signaling pathway leading to a change in nutrient transport. Animal models are important tools for systematically studying such complex events. Debate centers on whether the rodent placenta is an appropriate tool for investigating the alterations in the human placenta that result in IUGR. This review provides an overview of the alterations in expression and activity of nutrient transporters and alterations in signaling associated with IUGR and compares these findings in rodents and humans. In general, the data obtained by studies of the various types of rodent and human nutrient transporters are similar. However, direct comparison is complicated by the fact that the results of such studies are controversial even within the same species, making the interpretation of the results challenging. This difficulty could be due to the absence of guidelines of the experimental design and, especially in humans, the use of trophoblast cell culture studies instead of clinical trials. Nonetheless, developing new therapy concepts for IUGR will

Transplacental Nutrient Transport Mechanisms of Intrauterine Growth Restriction in Rodent Models and Humans

Directory of Open Access Journals (Sweden)

Elke Winterhager

2017-11-01

Full Text Available Although the causes of intrauterine growth restriction (IUGR have been intensively investigated, important information is still lacking about the role of the placenta as a link from adverse maternal environment to adverse pregnancy outcomes of IUGR and preterm birth. IUGR is associated with an increased risk of cardiovascular, metabolic, and neurological diseases later in life. Determination of the most important pathways that regulate transplacental transport systems is necessary for identifying marker genes as diagnostic tools and for developing drugs that target the molecular pathways. Besides oxygen, the main nutrients required for appropriate fetal development and growth are glucose, amino acids, and fatty acids. Dysfunction in transplacental transport is caused by impairments in both placental morphology and blood flow, as well as by factors such as alterations in the expression of insulin-like growth factors and changes in the mTOR signaling pathway leading to a change in nutrient transport. Animal models are important tools for systematically studying such complex events. Debate centers on whether the rodent placenta is an appropriate tool for investigating the alterations in the human placenta that result in IUGR. This review provides an overview of the alterations in expression and activity of nutrient transporters and alterations in signaling associated with IUGR and compares these findings in rodents and humans. In general, the data obtained by studies of the various types of rodent and human nutrient transporters are similar. However, direct comparison is complicated by the fact that the results of such studies are controversial even within the same species, making the interpretation of the results challenging. This difficulty could be due to the absence of guidelines of the experimental design and, especially in humans, the use of trophoblast cell culture studies instead of clinical trials. Nonetheless, developing new therapy

Mitogen activated protein kinase phosphatase-1 prevents the development of tactile sensitivity in a rodent model of neuropathic pain

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Ndong Christian

2012-04-01

Full Text Available Abstract Background Neuropathic pain due to nerve injury is one of the most difficult types of pain to treat. Following peripheral nerve injury, neuronal and glial plastic changes contribute to central sensitization and perpetuation of mechanical hypersensitivity in rodents. The mitogen activated protein kinase (MAPK family is pivotal in this spinal cord plasticity. MAPK phosphatases (MKPs limit inflammatory processes by dephosphorylating MAPKs. For example, MKP-1 preferentially dephosphorylates p-p38. Since spinal p-p38 is pivotal for the development of chronic hypersensitivity in rodent models of pain, and p-p38 inhibitors have shown clinical potential in acute and chronic pain patients, we hypothesize that induction of spinal MKP-1 will prevent the development of peripheral nerve-injury-induced hypersensitivity and p-p38 overexpression. Results We cloned rat spinal cord MKP-1 and optimize MKP-1 cDNA in vitro using transfections to BV-2 cells. We observed that in vitro overexpression of MKP-1 blocked lipopolysaccharide-induced phosphorylation of p38 (and other MAPKs as well as release of pro-algesic effectors (i.e., cytokines, chemokines, nitric oxide. Using this cDNA MKP-1 and a non-viral, in vivo nanoparticle transfection approach, we found that spinal cord overexpression of MKP-1 prevented development of peripheral nerve-injury-induced tactile hypersensitivity and reduced pro-inflammatory cytokines and chemokines and the phosphorylated form of p38. Conclusions Our results indicate that MKP-1, the natural regulator of p-p38, mediates resolution of the spinal cord pro-inflammatory milieu induced by peripheral nerve injury, resulting in prevention of chronic mechanical hypersensitivity. We propose that MKP-1 is a potential therapeutic target for pain treatment or prevention.

Characterization of rat model of acute anterior uveitis using optical coherence tomography angiography

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Choi, Woo June; Pepple, Kathryn L.; Zhi, Zhongwei; Wang, Ruikang K.

2015-03-01

Uveitis, or ocular inflammation, is a cause of severe visual impairment. Rodent models of uveitis are powerful tools used to investigate the pathological mechanisms of ocular inflammation and to study the efficacy of new therapies prior to human testing. In this paper, we report the utility of spectral-domain optical coherence tomography (SD-OCT) angiography in characterizing the inflammatory changes induced in the anterior segment of a rat model of uveitis. Acute anterior uveitis (AAU) was induced in two rats by intravitreal injection of a killed mycobacterial extract. One of them received a concurrent periocular injection of steroids to model a treatment effect. OCT imaging was performed prior to inflammation induction on day 0 (baseline), and 2 days post-injection (peak inflammation). Baseline and inflamed images were compared. OCT angiography identified swelling of the cornea, inflammatory cells in the anterior and posterior chambers, a fibrinous papillary membrane, and dilation of iris vessels in the inflamed eyes when compared to baseline images. Steroid treatment was shown to prevent the changes associated with inflammation. This is a novel application of anterior OCT imaging in animal models of uveitis, and provides a high resolution, in vivo assay for detecting and quantifying ocular inflammation and the response to new therapies.

Differential effects of subcutaneous electrical stimulation (SQS) and transcutaneous electrical nerve stimulation (TENS) in rodent models of chronic neuropathic or inflammatory pain.

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Vera-Portocarrero, Louis P; Cordero, Toni; Billstrom, Tina; Swearingen, Kim; Wacnik, Paul W; Johanek, Lisa M

2013-01-01

Electrical stimulation has been used for many years for the treatment of pain. Present-day research demonstrates that stimulation targets and parameters impact the induction of specific pain-modulating mechanisms. New targets are increasingly being investigated clinically, but the scientific rationale for a particular target is often not well established. This present study compares the behavioral effects of targeting peripheral axons by electrode placement in the subcutaneous space vs. electrode placement on the surface of the skin in a rodent model. Rodent models of inflammatory and neuropathic pain were used to investigate subcutaneous electrical stimulation (SQS) vs. transcutaneous electrical nerve stimulation (TENS). Electrical parameters and relative location of the leads were held constant under each condition. SQS had cumulative antihypersensitivity effects in both inflammatory and neuropathic pain rodent models, with significant inhibition of mechanical hypersensitivity observed on days 3-4 of treatment. In contrast, reduction of thermal hyperalgesia in the inflammatory model was observed during the first four days of treatment with SQS, and reduction of cold allodynia in the neuropathic pain model was seen only on the first day with SQS. TENS was effective in the inflammation model, and in agreement with previous studies, tolerance developed to the antihypersensitivity effects of TENS. With the exception of a reversal of cold hypersensitivity on day 1 of testing, TENS did not reveal significant analgesic effects in the neuropathic pain rodent model. The results presented show that TENS and SQS have different effects that could point to unique biologic mechanisms underlying the analgesic effect of each therapy. Furthermore, this study is the first to demonstrate in an animal model that SQS attenuates neuropathic and inflammatory-induced pain behaviors. © 2013 Medtronic, Inc.

Neurogenetics of aggressive behavior: studies in rodents.

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Takahashi, Aki; Miczek, Klaus A

2014-01-01

Aggressive behavior is observed in many animal species, such as insects, fish, lizards, frogs, and most mammals including humans. This wide range of conservation underscores the importance of aggressive behavior in the animals' survival and fitness, and the likely heritability of this behavior. Although typical patterns of aggressive behavior differ between species, there are several concordances in the neurobiology of aggression among rodents, primates, and humans. Studies with rodent models may eventually help us to understand the neurogenetic architecture of aggression in humans. However, it is important to recognize the difference between the ecological and ethological significance of aggressive behavior (species-typical aggression) and maladaptive violence (escalated aggression) when applying the findings of aggression research using animal models to human or veterinary medicine. Well-studied rodent models for aggressive behavior in the laboratory setting include the mouse (Mus musculus), rat (Rattus norvegicus), hamster (Mesocricetus auratus), and prairie vole (Microtus ochrogaster). The neural circuits of rodent aggression have been gradually elucidated by several techniques, e.g., immunohistochemistry of immediate-early gene (c-Fos) expression, intracranial drug microinjection, in vivo microdialysis, and optogenetics techniques. Also, evidence accumulated from the analysis of gene-knockout mice shows the involvement of several genes in aggression. Here, we review the brain circuits that have been implicated in aggression, such as the hypothalamus, prefrontal cortex (PFC), dorsal raphe nucleus (DRN), nucleus accumbens (NAc), and olfactory system. We then discuss the roles of glutamate and γ-aminobutyric acid (GABA), excitatory and inhibitory amino acids in the brain, as well as their receptors, in controlling aggressive behavior, focusing mainly on recent findings. At the end of this chapter, we discuss how genes can be identified that underlie individual

Intermittent Hypoxia and Stem Cell Implants Preserve Breathing Capacity in a Rodent Model of Amyotrophic Lateral Sclerosis

Science.gov (United States)

Nichols, Nicole L.; Gowing, Genevieve; Satriotomo, Irawan; Nashold, Lisa J.; Dale, Erica A.; Suzuki, Masatoshi; Avalos, Pablo; Mulcrone, Patrick L.; McHugh, Jacalyn

2013-01-01

Rationale: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease causing paralysis and death from respiratory failure. Strategies to preserve and/or restore respiratory function are critical for successful treatment. Although breathing capacity is maintained until late in disease progression in rodent models of familial ALS (SOD1G93A rats and mice), reduced numbers of phrenic motor neurons and decreased phrenic nerve activity are observed. Decreased phrenic motor output suggests imminent respiratory failure. Objectives: To preserve or restore phrenic nerve activity in SOD1G93A rats at disease end stage. Methods: SOD1G93A rats were injected with human neural progenitor cells (hNPCs) bracketing the phrenic motor nucleus before disease onset, or exposed to acute intermittent hypoxia (AIH) at disease end stage. Measurements and Main Results: The capacity to generate phrenic motor output in anesthetized rats at disease end stage was: (1) transiently restored by a single presentation of AIH; and (2) preserved ipsilateral to hNPC transplants made before disease onset. hNPC transplants improved ipsilateral phrenic motor neuron survival. Conclusions: AIH-induced respiratory plasticity and stem cell therapy have complementary translational potential to treat breathing deficits in patients with ALS. PMID:23220913

Glutamate and GABA in autism spectrum disorder-a translational magnetic resonance spectroscopy study in man and rodent models.

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Horder, Jamie; Petrinovic, Marija M; Mendez, Maria A; Bruns, Andreas; Takumi, Toru; Spooren, Will; Barker, Gareth J; Künnecke, Basil; Murphy, Declan G

2018-05-25

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental syndrome with a high human and economic burden. The pathophysiology of ASD is largely unclear, thus hampering development of pharmacological treatments for the core symptoms of the disorder. Abnormalities in glutamate and GABA signaling have been hypothesized to underlie ASD symptoms, and may form a therapeutic target, but it is not known whether these abnormalities are recapitulated in humans with ASD, as well as in rodent models of the disorder. We used translational proton magnetic resonance spectroscopy ([1H]MRS) to compare glutamate and GABA levels in adult humans with ASD and in a panel of six diverse rodent ASD models, encompassing genetic and environmental etiologies. [1H]MRS was performed in the striatum and the medial prefrontal cortex, of the humans, mice, and rats in order to allow for direct cross-species comparisons in specific cortical and subcortical brain regions implicated in ASD. In humans with ASD, glutamate concentration was reduced in the striatum and this was correlated with the severity of social symptoms. GABA levels were not altered in either brain region. The reduction in striatal glutamate was recapitulated in mice prenatally exposed to valproate, and in mice and rats carrying Nlgn3 mutations, but not in rodent ASD models with other etiologies. Our findings suggest that glutamate/GABA abnormalities in the corticostriatal circuitry may be a key pathological mechanism in ASD; and may be linked to alterations in the neuroligin-neurexin signaling complex.

21 CFR 1250.96 - Rodent control.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rodent control. 1250.96 Section 1250.96 Food and... SANITATION Sanitation Facilities and Conditions on Vessels § 1250.96 Rodent control. Vessels shall be... of rodent control. ...

Studies into abnormal aggression in humans and rodents: Methodological and translational aspects.

Science.gov (United States)

Haller, Jozsef

2017-05-01

Here we review the principles based on which aggression is rendered abnormal in humans and laboratory rodents, and comparatively overview the main methodological approaches based on which this behavior is studied in the two categories of subjects. It appears that the discriminating property of abnormal aggression is rule breaking, which renders aggression dysfunctional from the point of view of the perpetrator. We show that rodent models of abnormal aggression were created by the translation of human conditions into rodent equivalents, and discuss how findings obtained with such models may be "translated back" to human conditions when the mechanisms underlying aggression and its possibilities of treatment are investigated. We suggest that the complementary nature of human and rodent research approaches invite a more intense cross-talk between the two sides of aggression research than the one presently observed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Virtual reality systems for rodents.

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Thurley, Kay; Ayaz, Aslı

2017-02-01

Over the last decade virtual reality (VR) setups for rodents have been developed and utilized to investigate the neural foundations of behavior. Such VR systems became very popular since they allow the use of state-of-the-art techniques to measure neural activity in behaving rodents that cannot be easily used with classical behavior setups. Here, we provide an overview of rodent VR technologies and review recent results from related research. We discuss commonalities and differences as well as merits and issues of different approaches. A special focus is given to experimental (behavioral) paradigms in use. Finally we comment on possible use cases that may further exploit the potential of VR in rodent research and hence inspire future studies.

Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia

Directory of Open Access Journals (Sweden)

Wahl D

2017-09-01

Full Text Available Devin Wahl,1,2 Sean CP Coogan,1,3 Samantha M Solon-Biet,1,2 Rafael de Cabo,4 James B Haran,5 David Raubenheimer,1,6,7 Victoria C Cogger,1,2 Mark P Mattson,8 Stephen J Simpson,1,2,7 David G Le Couteur1,2 1Charles Perkins Centre, University of Sydney, Sydney, 2Aging and Alzheimers Institute, ANZAC Research Institute, Concord Clinical School/Sydney Medical School, Concord, NSW, Australia; 3Department of Renewable Resources, University of Alberta, Edmonton, AB, Canada; 4Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA; 5Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA; 6Faculty of Veterinary Science, 7School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia; 8Laboratory of Neurosciences, National Institute on Aging’s Intramural Research Program, National Institutes of Health, Baltimore, MD, USA Abstract: Evaluation of behavior and cognition in rodent models underpins mechanistic and interventional studies of brain aging and neurodegenerative diseases, especially ­dementia. Commonly used tests include Morris water maze, Barnes maze, object recognition, fear ­conditioning, radial arm water maze, and Y maze. Each of these tests reflects some aspects of human memory including episodic memory, recognition memory, semantic memory, spatial memory, and emotional memory. Although most interventional studies in rodent models of dementia have focused on pharmacological agents, there are an increasing number of studies that have evaluated nutritional interventions including caloric restriction, intermittent fasting, and manipulation of macronutrients. Dietary interventions have been shown to influence ­various cognitive and behavioral tests in rodents indicating that nutrition can influence brain aging and possibly neurodegeneration. Keywords: calorie restriction, intermittent fasting, aging, memory, macronutrients

Modeling natural photic entrainment in a subterranean rodent (Ctenomys aff. knighti, the Tuco-Tuco.

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Danilo E F L Flôres

Full Text Available Subterranean rodents spend most of the day inside underground tunnels, where there is little daily change in environmental variables. Our observations of tuco-tucos (Ctenomys aff. knighti in a field enclosure indicated that these animals perceive the aboveground light-dark cycle by several bouts of light-exposure at irregular times during the light hours of the day. To assess whether such light-dark pattern acts as an entraining agent of the circadian clock, we first constructed in laboratory the Phase Response Curve for 1 h light-pulses (1000lux. Its shape is qualitatively similar to other curves reported in the literature and to our knowledge it is the first Phase Response Curve of a subterranean rodent. Computer simulations were performed with a non-linear limit-cycle oscillator subjected to a simple model of the light regimen experienced by tuco-tucos. Results showed that synchronization is achieved even by a simple regimen of a single daily light pulse scattered uniformly along the light hours of the day. Natural entrainment studies benefit from integrated laboratory, field and computational approaches.

Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

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Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

2014-08-01

Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. Copyright © 2014 Elsevier Inc. All rights reserved.

Behavioral testing in rodent models of orofacial neuropathic and inflammatory pain

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Krzyzanowska, Agnieszka; Avendaño, Carlos

2012-01-01

Orofacial pain conditions are often very debilitating to the patient and difficult to treat. While clinical interest is high, the proportion of studies performed in the orofacial region in laboratory animals is relatively low, compared with other body regions. This is partly due to difficulties in testing freely moving animals and therefore lack of reliable testing methods. Here we present a comprehensive review of the currently used rodent models of inflammatory and neuropathic pain adapted to the orofacial areas, taking into account the difficulties and drawbacks of the existing approaches. We examine the available testing methods and procedures used for assessing the behavioral responses in the face in both mice and rats and provide a summary of some pharmacological agents used in these paradigms to date. The use of these agents in animal models is also compared with outcomes observed in the clinic. PMID:23139912

Aberrant dopamine D2-like receptor function in a rodent model of schizophrenia.

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Perez, Stephanie M; Lodge, Daniel J

2012-11-01

Based on the observation that antipsychotic medications display antagonist properties at dopamine D2-like receptors, aberrant dopamine signaling has been proposed to underlie psychosis in patients with schizophrenia. Thus, it is not surprising that considerable research has been devoted to understanding the mechanisms involved in the antipsychotic action of these compounds. It is important to note that the majority of these studies have been performed in "normal" experimental animals. Given that these animals do not possess the aberrant neuronal information processing typically associated with schizophrenia, the aim of the current study was to examine the dopamine D2 receptor system in a rodent model of schizophrenia. Here, we demonstrate that methylazoxymethanol acetate (MAM)-treated rats display an enhanced effect of quinpirole on dopamine neuron activity and an aberrant locomotor response to D2-like receptor activation, suggesting changes in postsynaptic D2-like receptor function. To better understand the mechanisms underlying the enhanced response to D2-like ligands in MAM-treated rats, we examined the expression of D2, D3, and dopamine transporter mRNA in the nucleus accumbens and ventral tegmental area by quantitative reverse transcription-polymerase chain reaction. MAM-treated rats displayed a significant increase in dopamine D3 receptor mRNA expression in the nucleus accumbens with no significant changes in the expression of the D2 receptor. Taken together, these data demonstrate robust alterations in dopamine D2-like receptor function in a rodent model of schizophrenia and provide evidence that preclinical studies examining the mechanisms of antipsychotic drug action should be performed in animal models that mirror aspects of the abnormal neuronal transmission thought to underlie symptoms of schizophrenia.

Comparing strategies for controlling an African pest rodent: an empirically based theoretical study

DEFF Research Database (Denmark)

Stenseth, Nils Chr.; Leirs, Herwig; Mercelis, Saskia

2001-01-01

of rats. Control measures affecting survival as well as reproduction were considered.4. The model showed that control measures reducing survival will only have long-term effects on population size if they are also applied when rodent densities are low. Control measures applied only when rodent densities...... are high will not have persistent effects, even at high mortality rates.5. The model demonstrated that control measures reducing reproduction are likely to prevent Mastomys outbreaks, but will keep densities low over a long period only when the contraceptive effect is strong (> 75% reduction).6. Provided...... in particular cause major economic losses in Africa through damage to crops. Attempts to develop dynamic population models for this and other pest rodents are ongoing. 2. Demographic estimates from a capture-mark-recapture (CMR) study in Tanzania were used to parameterize a population model for this species...

Bone morphology of the hind limbs in two caviomorph rodents.

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de Araújo, F A P; Sesoko, N F; Rahal, S C; Teixeira, C R; Müller, T R; Machado, M R F

2013-04-01

In order to evaluate the hind limbs of caviomorph rodents a descriptive analysis of the Cuniculus paca (Linnaeus, 1766) and Hydrochoerus hydrochaeris (Linnaeus, 1766) was performed using anatomical specimens, radiography, computed tomography (CT) and full-coloured prototype models to generate bone anatomy data. The appendicular skeleton of the two largest rodents of Neotropical America was compared with the previously reported anatomical features of Rattus norvegicus (Berkenhout, 1769) and domestic Cavia porcellus (Linnaeus, 1758). The structures were analyzed macroscopically and particular findings of each species reported. Features including the presence of articular fibular projection and lunulae were observed in the stifle joint of all rodents. Imaging aided in anatomical description and, specifically in the identification of bone structures in Cuniculus paca and Hydrochoerus hydrochaeris. The imaging findings were correlated with the anatomical structures observed. The data may be used in future studies comparing these animals to other rodents and mammalian species. © 2012 Blackwell Verlag GmbH.

Reliable critical sized defect rodent model for cleft palate research.

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Mostafa, Nesrine Z; Doschak, Michael R; Major, Paul W; Talwar, Reena

2014-12-01

Suitable animal models are necessary to test the efficacy of new bone grafting therapies in cleft palate surgery. Rodent models of cleft palate are available but have limitations. This study compared and modified mid-palate cleft (MPC) and alveolar cleft (AC) models to determine the most reliable and reproducible model for bone grafting studies. Published MPC model (9 × 5 × 3 mm(3)) lacked sufficient information for tested rats. Our initial studies utilizing AC model (7 × 4 × 3 mm(3)) in 8 and 16 weeks old Sprague Dawley (SD) rats revealed injury to adjacent structures. After comparing anteroposterior and transverse maxillary dimensions in 16 weeks old SD and Wistar rats, virtual planning was performed to modify MPC and AC defects dimensions, taking the adjacent structures into consideration. Modified MPC (7 × 2.5 × 1 mm(3)) and AC (5 × 2.5 × 1 mm(3)) defects were employed in 16 weeks old Wistar rats and healing was monitored by micro-computed tomography and histology. Maxillary dimensions in SD and Wistar rats were not significantly different. Preoperative virtual planning enhanced postoperative surgical outcomes. Bone healing occurred at defect margin leaving central bone void confirming the critical size nature of the modified MPC and AC defects. Presented modifications for MPC and AC models created clinically relevant and reproducible defects. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Stress in adolescence and drugs of abuse in rodent models: Role of dopamine, CRF, and HPA axis

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Burke, Andrew R.; Miczek, Klaus A.

2014-01-01

Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse. Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic pituitary adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms. Results and Conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse. PMID:24370534

Vision in laboratory rodents-Tools to measure it and implications for behavioral research.

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Leinonen, Henri; Tanila, Heikki

2017-07-29

Mice and rats are nocturnal mammals and their vision is specialized for detection of motion and contrast in dim light conditions. These species possess a large proportion of UV-sensitive cones in their retinas and the majority of their optic nerve axons target superior colliculus rather than visual cortex. Therefore, it was a widely held belief that laboratory rodents hardly utilize vision during day-time behavior. This dogma is being questioned as accumulating evidence suggests that laboratory rodents are able to perform complex visual functions, such as perceiving subjective contours, and that declined vision may affect their performance in many behavioral tasks. For instance, genetic engineering may have unexpected consequences on vision as mouse models of Alzheimer's and Huntington's diseases have declined visual function. Rodent vision can be tested in numerous ways using operant training or reflex-based behavioral tasks, or alternatively using electrophysiological recordings. In this article, we will first provide a summary of visual system and explain its characteristics unique to rodents. Then, we present well-established techniques to test rodent vision, with an emphasis on pattern vision: visual water test, optomotor reflex test, pattern electroretinography and pattern visual evoked potentials. Finally, we highlight the importance of visual phenotyping in rodents. As the number of genetically engineered rodent models and volume of behavioral testing increase simultaneously, the possibility of visual dysfunctions needs to be addressed. Neglect in this matter potentially leads to crude biases in the field of neuroscience and beyond. Copyright © 2017 Elsevier B.V. All rights reserved.

A putative low-carbohydrate ketogenic diet elicits mild nutritional ketosis but does not impair the acute or chronic hypertrophic responses to resistance exercise in rodents.

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Roberts, Michael D; Holland, A Maleah; Kephart, Wesley C; Mobley, C Brooks; Mumford, Petey W; Lowery, Ryan P; Fox, Carlton D; McCloskey, Anna E; Shake, Joshua J; Mesquita, Paulo; Patel, Romil K; Martin, Jeffrey S; Young, Kaelin C; Kavazis, Andreas N; Wilson, Jacob M

2016-05-15

We examined whether acute and/or chronic skeletal muscle anabolism is impaired with a low-carbohydrate diet formulated to elicit ketosis (LCKD) vs. a mixed macronutrient Western diet (WD). Male Sprague-Dawley rats (9-10 wk of age, 300-325 g) were provided isoenergetic amounts of a LCKD or a WD for 6 wk. In AIM 1, basal serum and gastrocnemius assessments were performed. In AIM 2, rats were resistance exercised for one bout and were euthanized 90-270 min following exercise for gastrocnemius analyses. In AIM 3, rats voluntarily exercised daily with resistance-loaded running wheels, and hind limb muscles were analyzed for hypertrophy markers at the end of the 6-wk protocol. In AIM 1, basal levels of gastrocnemius phosphorylated (p)-rps6, p-4EBP1, and p-AMPKα were similar between diets, although serum insulin (P ketosis, as the LCKD-fed rats in AIM 2 exhibited ∼1.5-fold greater serum β-hydroxybutyrate levels relative to WD-fed rats (diet effect P = 0.003). This study demonstrates that the tested LCKD in rodents, while only eliciting mild nutritional ketosis, does not impair the acute or chronic skeletal muscle hypertrophic responses to resistance exercise. Copyright © 2016 the American Physiological Society.

The effect of tear size and nerve injury on rotator cuff muscle fatty degeneration in a rodent animal model.

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Kim, H Mike; Galatz, Leesa M; Lim, Chanteak; Havlioglu, Necat; Thomopoulos, Stavros

2012-07-01

Irreversible muscle changes after rotator cuff tears is a well-known negative prognostic factor after shoulder surgery. Currently, little is known about the pathomechanism of fatty degeneration of the rotator cuff muscles after chronic cuff tears. The purposes of this study were to (1) develop a rodent animal model of chronic rotator cuff tears that can reproduce fatty degeneration of the cuff muscles seen clinically, (2) describe the effects of tear size and concomitant nerve injury on muscle degeneration, and (3) evaluate the changes in gene expression of relevant myogenic and adipogenic factors after rotator cuff tears using the animal model. Rotator cuff tears were created in rodents with and without transection of the suprascapular nerve. The supraspinatus and infraspinatus muscles were examined at 2, 8, and 16 weeks after injury for histologic evidence of fatty degeneration and expression of myogenic and adipogenic genes. Histologic analysis revealed adipocytes, intramuscular fat globules, and intramyocellular fat droplets in the tenotomized and neurotomized supraspinatus and infraspinatus muscles. Changes increased with time and were most severe in the muscles with combined tenotomy and neurotomy. Adipogenic and myogenic transcription factors and markers were upregulated in muscles treated with tenotomy or tenotomy combined with neurotomy compared with normal muscles. The rodent animal model described in this study produces fatty degeneration of the rotator cuff muscles similar to human muscles after chronic cuff tears. The severity of changes was associated with tear size and concomitant nerve injury. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

A biometric approach to laboratory rodent identification.

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Cameron, Jens; Jacobson, Christina; Nilsson, Kenneth; Rögnvaldsson, Thorsteinn

2007-03-01

Individual identification of laboratory rodents typically involves invasive methods, such as tattoos, ear clips, and implanted transponders. Beyond the ethical dilemmas they may present, these methods may cause pain or distress that confounds research results. The authors describe a prototype device for biometric identification of laboratory rodents that would allow researchers to identify rodents without the complications of other methods. The device, which uses the rodent's ear blood vessel pattern as the identifier, is fast, automatic, noninvasive, and painless.

Characterizing low dose and dose rate effects in rodent and human neural stem cells exposed to proton and gamma irradiation

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Bertrand P. Tseng

2013-01-01

Full Text Available Past work has shown that exposure to gamma rays and protons elicit a persistent oxidative stress in rodent and human neural stem cells (hNSCs. We have now adapted these studies to more realistic exposure scenarios in space, using lower doses and dose rates of these radiation modalities, to further elucidate the role of radiation-induced oxidative stress in these cells. Rodent neural stem and precursor cells grown as neurospheres and human neural stem cells grown as monolayers were subjected to acute and multi-dosing paradigms at differing dose rates and analyzed for changes in reactive oxygen species (ROS, reactive nitrogen species (RNS, nitric oxide and superoxide for 2 days after irradiation. While acute exposures led to significant changes in both cell types, hNSCs in particular, exhibited marked and significant elevations in radiation-induced oxidative stress. Elevated oxidative stress was more significant in hNSCs as opposed to their rodent counterparts, and hNSCs were significantly more sensitive to low dose exposures in terms of survival. Combinations of protons and γ-rays delivered as lower priming or higher challenge doses elicited radioadaptive changes that were associated with improved survival, but in general, only under conditions where the levels of reactive species were suppressed compared to cells irradiated acutely. Protective radioadaptive effects on survival were eliminated in the presence of the antioxidant N-acetylcysteine, suggesting further that radiation-induced oxidative stress could activate pro-survival signaling pathways that were sensitive to redox state. Data corroborates much of our past work and shows that low dose and dose rate exposures elicit significant changes in oxidative stress that have functional consequences on survival.

Odor supported place cell model and goal navigation in rodents

DEFF Research Database (Denmark)

Kulvicius, Tomas; Tamosiunaite, Minija; Ainge, James

2008-01-01

Experiments with rodents demonstrate that visual cues play an important role in the control of hippocampal place cells and spatial navigation. Nevertheless, rats may also rely on auditory, olfactory and somatosensory stimuli for orientation. It is also known that rats can track odors or self......-generated scent marks to find a food source. Here we model odor supported place cells by using a simple feed-forward network and analyze the impact of olfactory cues on place cell formation and spatial navigation. The obtained place cells are used to solve a goal navigation task by a novel mechanism based on self......-marking by odor patches combined with a Q-learning algorithm. We also analyze the impact of place cell remapping on goal directed behavior when switching between two environments. We emphasize the importance of olfactory cues in place cell formation and show that the utility of environmental and self...

Evaluation of cytotoxic effects and acute and chronic toxicity of aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) in rodents.

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Lyoussi, Badiaa; Cherkaoui Tangi, Khadija; Morel, Nicole; Haddad, Mohamed; Quetin-Leclercq, Joelle

2018-01-01

The present investigation was carried out to evaluate the safety of an aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) by determining its cytotoxicity and potential toxicity after acute and sub-chronic administration in rodents. Cytotoxic activity was tested in cancer and non-cancer cell lines HeLa, Mel-5, HL-60 and 3T3. Acute toxicity tests were carried out in mice by a single oral administration of Calycotome seed-extract (0 - 12 g/kg) as well as intraperitoneal doses of 0 - 5 g/kg. Sub-chronic studies were conducted in Wistar rats by administration of oral daily doses for up to 90 days. Changes in body and vital organ weights, mortality, haematology, clinical biochemistry and histologic morphology were evaluated. The lyophilized aqueous extract of C. villosa exhibited a low cytotoxicity in all cell lines tested with an IC 50 > 100 µg/ml. In the acute study in mice, intra-peritoneal administration caused dose-dependent adverse effects and mortality with an LD 50 of 4.06 ± 0.01 g/kg. In the chronic tests, neither mortality nor visible signs of lethality was seen in rats. Even AST and ALT were not affected while a significant decrease in serum glucose levels, at 300 and 600 mg/kg was detected. Histopathological examination of the kidney and liver did not show any alteration or inflammation at the end of treatment. In conclusion, the aqueous extract of C. villosa seed appeared to be non-toxic and did not produce mortality or clinically significant changes in the haematological and biochemical parameters in rats.

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

Science.gov (United States)

Zhan, Xianbao; Wang, Fan; Bi, Yan

2016-01-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. PMID:27418683

The rodent ultrasound production mechanism.

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Roberts, L H

1975-03-01

Rodents produce two types of sounds, audible and ultrasonic, that differ markedly in physical structure. Studies of sound production in light gases show that whereas the audible cries appear to be produced, as in the case of most other mammals, by vibrating structures in the larynx, the ultrasonic cries are produced by a different mechanism, probably a whistle. 'Bird-call' whistles are shown to have all the properties of rodent ultrasonic cries and to mimic them in almost every detail. Thus it is concluded that rodents have two distinct sound production mechanisms, one for audible cries and one for ultrasonic cries.

Accelerated cognitive decline in a rodent model for temporal lobe epilepsy

NARCIS (Netherlands)

Schipper, Sandra; Aalbers, Marlien W.; Rijkers, Kim; Lagiere, Melanie; Bogaarts, Jan G.; Blokland, Arjan; Klinkenberg, Sylvia; Hoogland, Govert; Vles, Johan S. H.

2016-01-01

Objective: Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent

A Biomathematical Model of Lymphopoiesis and Its Application to Acute and Chronic Irradiation Assessment

Science.gov (United States)

Hu, Shaowen; Cucinotta, Francis A.

2010-01-01

After the events of September 11, 2001, there is an increasing concern of the occurrence of radiological terrorism that may result in significant casualties in densely populated areas. Much effort has been made to establish various biomarkers to rapidly assess radiation dose in mass-casualty and population-monitoring scenarios, which are demanded for effective medical management and treatment of the exposed victims. Among these the count of lymphocytes in peripheral blood and their depletion kinetics are the most important early indicators of the severity of the radiation injury. In this study, we examine a biomathematical model of lymphopoiesis which has been successfully utilized to simulate and interpret experimental data of acute and chronic irradiations on rodents [1]. With revised parameters for humans, we find this model can reproduce several sets of clinical lymphocyte data of accident victims over a wide range of absorbed doses. In addition, the absolute lymphocyte counts and the depletion rate constants calculated by this model also show good correlation with the Guskova formula and the Goans model, the two empirical tools which have been widely recognized for early estimation of the exposed dose after radiation accidents [2]. We also use the model to analyze the hematological data of the Techa River residents which were exposed to chronic low-dose irradiation during 1950-1956 [3]. This model can serve as a computational tool in radiation accident management, military operations involving nuclear warfare, radiation therapy, and space radiation risk assessment.

The effects of acute and chronic estrogen deficiency on glucose and lipid profile in ovariectomized rats

OpenAIRE

Rabie P; Namjoo AR

2017-01-01

Background and aims: Ovariectomy is a standard experimental model of menopause in rodent to investigate postmenopausal women. The aim of this study was to evaluate effects acute and chronic estrogen deficiency on lipid profile and glucose serum in ovariectomized (OVX) rats. Methods: In this experimental study, Twenty-four adult female Wistar rats were divided into three groups of eight rats. The first group: sham-control, Second group: ovariectomized rats (for five weeks), Third group: Ova...

Using tests and models to assess antidepressant-like activity in rodents

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Kedzierska Ewa

2016-06-01

Full Text Available In today's world, depression is one of the more prevalent forms of mental illness. According to WHO, about 10%-30% of all women and 7%-15% of all men are afflicted by depression at least once in their life-times. Today, depression is assessed to be affecting 350 million people. Regarding this issue, an important challenge for current psychopharmacology is to develop new, more effective pharmacotherapy and to understand the mechanism of action of known antidepressants. Furthermore, there is the necessity to improve the effectiveness of anti-depression treatment by way of bringing about an understanding of the neurobiology of this illness. In achieving these objectives, animal models of depression can be useful. Yet, presently, all available animal models of depression rely on two principles: the actions of known antidepressants or the responses to stress. In this paper, we present an overview of the most widely used animal tests and models that are employed in assessing antidepressant-like activity in rodents. These include amphetamine potentiation, reversal of reserpine action, the forced swimming test, the tail suspension test, learned helplessness, chronic mild stress and social defeat stress. Moreover, the advantages and major drawbacks of each model are also discussed.

Experimental models of hepatotoxicity related to acute liver failure

Energy Technology Data Exchange (ETDEWEB)

Maes, Michaël [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Vinken, Mathieu, E-mail: mvinken@vub.ac.be [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Jaeschke, Hartmut [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City (United States)

2016-01-01

Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. - Highlights: • The murine APAP model is very close to what is observed in patients. • The Gal/ET model is useful to study TNFα-mediated apoptotic signaling mechanisms. • Fas receptor activation is an effective model of apoptosis and secondary necrosis. • The ConA model is a relevant model of auto-immune hepatitis and viral hepatitis. • Multiple time point evaluation needed in experimental models of acute liver injury.

The brain acid-base homeostasis and serotonin: A perspective on the use of carbon dioxide as human and rodent experimental model of panic.

Science.gov (United States)

Leibold, N K; van den Hove, D L A; Esquivel, G; De Cort, K; Goossens, L; Strackx, E; Buchanan, G F; Steinbusch, H W M; Lesch, K P; Schruers, K R J

2015-06-01

Panic attacks (PAs), the core feature of panic disorder, represent a common phenomenon in the general adult population and are associated with a considerable decrease in quality of life and high health care costs. To date, the underlying pathophysiology of PAs is not well understood. A unique feature of PAs is that they represent a rare example of a psychopathological phenomenon that can be reliably modeled in the laboratory in panic disorder patients and healthy volunteers. The most effective techniques to experimentally trigger PAs are those that acutely disturb the acid-base homeostasis in the brain: inhalation of carbon dioxide (CO2), hyperventilation, and lactate infusion. This review particularly focuses on the use of CO2 inhalation in humans and rodents as an experimental model of panic. Besides highlighting the different methodological approaches, the cardio-respiratory and the endocrine responses to CO2 inhalation are summarized. In addition, the relationships between CO2 level, changes in brain pH, the serotonergic system, and adaptive physiological and behavioral responses to CO2 exposure are presented. We aim to present an integrated psychological and neurobiological perspective. Remaining gaps in the literature and future perspectives are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acute traumatic spinal cord injury induces glial activation in the cynomolgus macaque (Macaca fascicularis).

Science.gov (United States)

Miller, A D; Westmoreland, S V; Evangelous, N R; Graham, A; Sledge, J; Nesathurai, S

2012-06-01

Traumatic spinal cord injury leads to direct myelin and axonal damage and leads to the recruitment of inflammatory cells to site of injury. Although rodent models have provided the greatest insight into the genesis of traumatic spinal cord injury (TSCI), recent studies have attempted to develop an appropriate non-human primate model. We explored TSCI in a cynomolgus macaque model using a balloon catheter to mimic external trauma to further evaluate the underlying mechanisms of acute TSCI. Following 1hour of spinal cord trauma, there were focal areas of hemorrhage and necrosis at the site of trauma. Additionally, there was a marked increased expression of macrophage-related protein 8, MMP9, IBA-1, and inducible nitric oxide synthase in macrophages and microglia at the site of injury. This data indicate that acute TSCI in the cynomolgus macaque is an appropriate model and that the earliest immunohistochemical changes noted are within macrophage and microglia populations. © 2012 John Wiley & Sons A/S.

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.

Science.gov (United States)

Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

2016-09-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. Copyright © 2016 the American Physiological Society.

Wild Rodent Ectoparasites Collected from Northwestern Iran

Directory of Open Access Journals (Sweden)

Zabihollah Zarei

2017-04-01

Full Text Available Background: Rodents play an important role as reservoir of some pathogens, and the host of some ectoparasites as well. These ectoparasites can transmit rodents’ pathogens to human or animals. The aim of this study was to assess the distribution and infestation load of ectoparasites on rodents in Meshkin-Shahr District, northwestern Iran.Method: Rodents were captured using baited live traps in spring 2014 from Meshkin-Shahr District and were trans­ferred to the laboratory for identification to the species level. Their ectoparasites were collected, mounted and identi­fied.Results: Three rodent species including Meriones persicus (74%, Mus musculus (16.9% and Cricetulus migrato­rius (9% were identified. Among all rodents, 185 specimens (90.69% were infested with a total of 521 ectopara­sites. Overall, 10 arthropods species were collected, including fleas (97.6%, one mite (1.6% and one louse species (0.6% as follows: Xenopsylla nubica, X. astia, X. buxtoni, X. cheopis, Nosopsyllus fasciatus, N. iranus, Cten­ocephalides felis, Ctenophthalmus rettigismiti, Ornithonyssus sp and one species of genus Polyplax. The most prev­alent ectoparasites species was X. nubica (89%.Conclusion: Nearly all rodent species were infested with Xenopsylla species. Monitoring of ectoparasites on infested rodents is very important for awareness and early warning towards control of arthropod-borne diseases.

Brain and behavioral pathology in an animal model of Wernicke's encephalopathy and Wernicke-Korsakoff Syndrome.

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Vetreno, Ryan P; Ramos, Raddy L; Anzalone, Steven; Savage, Lisa M

2012-02-03

Animal models provide the opportunity for in-depth and experimental investigation into the anatomical and physiological underpinnings of human neurological disorders. Rodent models of thiamine deficiency have yielded significant insight into the structural, neurochemical and cognitive deficits associated with thiamine deficiency as well as proven useful toward greater understanding of memory function in the intact brain. In this review, we discuss the anatomical, neurochemical and behavioral changes that occur during the acute and chronic phases of thiamine deficiency and describe how rodent models of Wernicke-Korsakoff Syndrome aid in developing a more detailed picture of brain structures involved in learning and memory. Copyright © 2011 Elsevier B.V. All rights reserved.

An improved cost-effective, reproducible method for evaluation of bone loss in a rodent model.

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Fine, Daniel H; Schreiner, Helen; Nasri-Heir, Cibele; Greenberg, Barbara; Jiang, Shuying; Markowitz, Kenneth; Furgang, David

2009-02-01

This study was designed to investigate the utility of two "new" definitions for assessment of bone loss in a rodent model of periodontitis. Eighteen rats were divided into three groups. Group 1 was infected by Aggregatibacter actinomycetemcomitans (Aa), group 2 was infected with an Aa leukotoxin knock-out, and group 3 received no Aa (controls). Microbial sampling and antibody titres were determined. Initially, two examiners measured the distance from the cemento-enamel-junction to alveolar bone crest using the three following methods; (1) total area of bone loss by radiograph, (2) linear bone loss by radiograph, (3) a direct visual measurement (DVM) of horizontal bone loss. Two "new" definitions were adopted; (1) any site in infected animals showing bone loss >2 standard deviations above the mean seen at that site in control animals was recorded as bone loss, (2) any animal with two or more sites in any quadrant affected by bone loss was considered as diseased. Using the "new" definitions both evaluators independently found that infected animals had significantly more disease than controls (DVM system; p<0.05). The DVM method provides a simple, cost effective, and reproducible method for studying periodontal disease in rodents.

Functionally-ecological role of biodiversity of small rodents population to ionizing radiation response

International Nuclear Information System (INIS)

Grigorkina, E.B.; Olenev, G.V.; Tarasov, O.V.

2014-01-01

Full text : In the present work it is aimed to show the results of investigations of radioresistance and biological effects of acute irradiation in laboratory experiment and the specific rate of 90Sr accumulation in the bone tissue of rodents of alternative types of ontogeny development. It is used the functional ontogeny approach, which supposes to divide natural population of mice and voles into groups of individuals with the same functional status and with the uniform patterns of growth or maturation rate as well as whether they participate in reproduction

OBscure but not OBsolete: Perturbations of the frontal cortex in common between rodent olfactory bulbectomy model and major depression.

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Rajkumar, Ramamoorthy; Dawe, Gavin S

2018-04-07

Olfactory bulbectomy (OBX) has been used as a model of depression over several decades. This model presupposes a mechanism that is still not proven in clinical depression. A wealth of clinical literature has focused on the derangements in frontal cortex (prefrontal, orbitofrontal and anterior cingulate cortices) associated with depression. In this comprehensive review, anatomical, electrophysiological and molecular sequelae of bulbectomy in the rodent frontal cortex are explored and compared with findings on brains of humans with major depression. Certain commonalities in neurobiological features of the perturbed frontal cortex in the bulbectomised rodent and the depressed human brain are evident. Also, meta-analysis reports on clinical studies on depressed patients provide prima facie evidence that perturbations in the frontal cortex are associated with major depression. Analysing the pattern of perturbations in the chemical neuroanatomy of the frontal cortex will contribute to understanding of the neurobiology of depression. Revisiting the OBX model of depression to examine these neurobiological changes in frontal cortex with contemporary imaging, proteomics, lipidomics, metabolomics and epigenomics technologies is proposed as an approach to enhance the translational value of this animal model to facilitate identification of targets and biomarkers for clinical depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Brain and Behavioral Pathology in an Animal Model of Wernicke’s Encephalopathy and Wernicke-Korsakoff Syndrome

Science.gov (United States)

Vetreno, Ryan P.; Ramos, Raddy L.; Anzalone, Steven; Savage, Lisa M.

2012-01-01

Animal models provide the opportunity for in-depth and experimental investigation into the anatomical and physiological underpinnings of human neurological disorders. Rodent models of thiamine deficiency have yielded significant insight into the structural, neurochemical and cognitive deficits associated with thiamine deficiency as well as proven useful toward greater understanding of memory function in the intact brain. In this review, we discuss the anatomical, neurochemical and behavioral changes that occur during the acute and chronic phases of thiamine deficiency and describe how rodent models of Wernicke-Korsakoff Syndrome aid in developing a more detailed picture of brain structures involved in learning and memory. PMID:22192411

Modeling and Hemofiltration Treatment of Acute Inflammation

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Robert S. Parker

2016-10-01

Full Text Available The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL-6, tumor necrosis factor (TNF, and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC algorithm was synthesized to control a hemoadsorption (HA device, a blood purification treatment for acute inflammation. A particle filter (PF algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i the apparent primary mechanism of HA efficacy is white blood cell (WBC capture, with cytokine capture a secondary benefit; and (ii differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.

Comprehensive evaluation of peripheral nerve regeneration in the acute healing phase using tissue clearing and optical microscopy in a rodent model.

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Yookyung Jung

Full Text Available Peripheral nerve injury (PNI, a common injury in both the civilian and military arenas, is usually associated with high healthcare costs and with patients enduring slow recovery times, diminished quality of life, and potential long-term disability. Patients with PNI typically undergo complex interventions but the factors that govern optimal response are not fully characterized. A fundamental understanding of the cellular and tissue-level events in the immediate postoperative period is essential for improving treatment and optimizing repair. Here, we demonstrate a comprehensive imaging approach to evaluate peripheral nerve axonal regeneration in a rodent PNI model using a tissue clearing method to improve depth penetration while preserving neural architecture. Sciatic nerve transaction and end-to-end repair were performed in both wild type and thy-1 GFP rats. The nerves were harvested at time points after repair before undergoing whole mount immunofluorescence staining and tissue clearing. By increasing the optic depth penetration, tissue clearing allowed the visualization and evaluation of Wallerian degeneration and nerve regrowth throughout entire sciatic nerves with subcellular resolution. The tissue clearing protocol did not affect immunofluorescence labeling and no observable decrease in the fluorescence signal was observed. Large-area, high-resolution tissue volumes could be quantified to provide structural and connectivity information not available from current gold-standard approaches for evaluating axonal regeneration following PNI. The results are suggestive of observed behavioral recovery in vivo after neurorrhaphy, providing a method of evaluating axonal regeneration following repair that can serve as an adjunct to current standard outcomes measurements. This study demonstrates that tissue clearing following whole mount immunofluorescence staining enables the complete visualization and quantitative evaluation of axons throughout

An assessment of the utilization of the preclinical rodent model literature in clinical trials of putative therapeutics for the treatment of alcohol use disorders.

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Barajaz, Ashley M; Kliethermes, Christopher L

2017-12-01

Rodent models of Alcohol Use Disorders (AUD) are used extensively by preclinical researchers to develop new therapeutics for the treatment of AUD. Although these models play an important role in the development of novel, targeted therapeutics, their role in bringing therapeutics to clinical trials is unclear, as off-label use of existing medications not approved for the treatment of AUD is commonly seen in the clinic and clinical trials. In the current study, we used the Clinicaltrials.gov database to obtain a list of drugs that have been tested for efficacy in a clinical trial between 1997 and 2017. We then conducted a set of literature searches to determine which of the 98 unique drugs we identified had shown efficacy in a rodent model of an AUD prior to being tested in a clinical trial. We found that slightly less than half of the drugs tested in clinical trials (48%) had shown prior efficacy in any rodent model of an AUD, while the remaining 52% of drugs were used off-label, or in some cases, following non-published studies. This study raises the question of how clinical researchers incorporate results from preclinical studies in the decision to bring a drug to a clinical trial. Our results underscore the need for ongoing communication among preclinical and clinical researchers. Copyright © 2017 Elsevier B.V. All rights reserved.

Simultaneous Expression from Both the Sense and Antisense Strand of the Erythropoietin Receptor Gene Mitigates Acute Lung Injury

Science.gov (United States)

2017-09-01

concept efficacy that increasing EpoR or RopE expression by cDNA delivery to lung cells in vitro enhances cytoprotection against hyperoxia-induced injury...oxidative damage, cell culture, rodent model, inhalation cDNA delivery, sense and antisense erythropoietin receptor transcripts 16. SECURITY...prevention of acute lung injury. 1-6 50% Subtask 1: Prepare plasmid cDNA of EpoR and RopE in nanoparticle formulation. 1 Completed 06.2017 Subtask 2

Early life stress paradigms in rodents: potential animal models of depression?

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Schmidt, Mathias V; Wang, Xiao-Dong; Meijer, Onno C

2011-03-01

While human depressive illness is indeed uniquely human, many of its symptoms may be modeled in rodents. Based on human etiology, the assumption has been made that depression-like behavior in rats and mice can be modulated by some of the powerful early life programming effects that are known to occur after manipulations in the first weeks of life. Here we review the evidence that is available in literature for early life manipulation as risk factors for the development of depression-like symptoms such as anhedonia, passive coping strategies, and neuroendocrine changes. Early life paradigms that were evaluated include early handling, separation, and deprivation protocols, as well as enriched and impoverished environments. We have also included a small number of stress-related pharmacological models. We find that for most early life paradigms per se, the actual validity for depression is limited. A number of models have not been tested with respect to classical depression-like behaviors, while in many cases, the outcome of such experiments is variable and depends on strain and additional factors. Because programming effects confer vulnerability rather than disease, a number of paradigms hold promise for usefulness in depression research, in combination with the proper genetic background and adult life challenges.

Effect of tramadol on pain-related behaviors and bladder overactivity in rodent cystitis models.

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Oyama, Tatsuya; Homan, Takashi; Kyotani, Junko; Oka, Michiko

2012-02-15

Tramadol is a widely used analgesic that stimulates the μ opioid receptor and inhibits serotonin and noradrenalin reuptake. There have been studies on the analgesic effects of tramadol based on the tail-flick test, the formalin test, and the induction of allodynia by sciatic-nerve ligation. However, the effects of tramadol on behaviors related to bladder pain and bladder overactivity induced by cystitis have not been reported. To investigate the usefulness of tramadol for patients with cystitis, we investigated these effects of tramadol in rodent cystitis models. Intraperitoneal injection of cyclophosphamide caused bladder-specific inflammation and increases in pain-related behaviors, the number of voids and bladder weight in mice. Tramadol suppressed the cyclophosphamide-induced pain-related behaviors but did not affect the number of voids or the bladder weight. During continuous-infusion cystometrograms in anesthetized rats, cyclophosphamide shortened the intercontraction interval, indicating bladder overactivity. Tramadol significantly prolonged the intercontraction interval, and the effect was partially blocked by the opioid antagonist naloxone. This finding indicates that μ opioid receptors may be involved in the action of tramadol. In conclusion, tramadol ameliorated cyclophosphamide-induced bladder-pain-related behaviors and bladder overactivity in rodents. These findings suggest that tramadol might be a treatment option for cystitis-induced bladder pain and bladder overactivity. Copyright © 2011 Elsevier B.V. All rights reserved.

Protective effects of hydroxytyrosol-supplemented refined olive oil in animal models of acute inflammation and rheumatoid arthritis.

Science.gov (United States)

Silva, S; Sepodes, B; Rocha, J; Direito, R; Fernandes, A; Brites, D; Freitas, M; Fernandes, E; Bronze, M R; Figueira, M E

2015-04-01

Virgin olive oil is the primary source of fat in the Mediterranean diet, and its beneficial health effects have been related with oleic acid and phenolic compounds content. Hydroxytyrosol, a typical virgin olive oil phenolic compound, has beneficial antioxidant and anti-inflammatory properties as previously reported. The aim of this study was to evaluate the effect of hydroxytyrosol-supplemented refined olive oil at 0.5 and 5 mg/kg in a rodent model of rheumatoid arthritis. Rheumatoid arthritis was induced by intradermic administration, in male Wistar rats, of Freund's adjuvant with collagen type II on days 1 and 21. Hydroxytyrosol-supplemented refined olive oils were administrated by gavage from day 23 until day 35. The treatment at 5-mg/kg dose significantly decreased paw edema (P<.01), histological damage, cyclooxygenase-2 and inducible nitric oxide synthase expression, and markedly reduced the degree of bone resorption, soft tissue swelling and osteophyte formation, improving articular function in treated animals. Acute inflammation, induced by carrageenan, was also evaluated for hydroxytyrosol-supplemented refined olive oils at 0.5 and 5 mg/kg. Both doses significantly reduced paw edema (P<.001). Our results suggest that the supplementation of refined olive oil with hydroxytyrosol may be advantageous in rheumatoid arthritis with significant impact not only on chronic inflammation but also on acute inflammatory processes. Copyright © 2015 Elsevier Inc. All rights reserved.

Rodent models of adaptive decision making.

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Izquierdo, Alicia; Belcher, Annabelle M

2012-01-01

Adaptive decision making affords the animal the ability to respond quickly to changes in a dynamic environment: one in which attentional demands, cost or effort to procure the reward, and reward contingencies change frequently. The more flexible the organism is in adapting choice behavior, the more command and success the organism has in navigating its environment. Maladaptive decision making is at the heart of much neuropsychiatric disease, including addiction. Thus, a better understanding of the mechanisms that underlie normal, adaptive decision making helps achieve a better understanding of certain diseases that incorporate maladaptive decision making as a core feature. This chapter presents three general domains of methods that the experimenter can manipulate in animal decision-making tasks: attention, effort, and reward contingency. Here, we present detailed methods of rodent tasks frequently employed within these domains: the Attentional Set-Shift Task, Effortful T-maze Task, and Visual Discrimination Reversal Learning. These tasks all recruit regions within the frontal cortex and the striatum, and performance is heavily modulated by the neurotransmitter dopamine, making these assays highly valid measures in the study of psychostimulant addiction.

Systems biology integration of proteomic data in rodent models of depression reveals involvement of the immune response and glutamatergic signaling.

Science.gov (United States)

Carboni, Lucia; Nguyen, Thanh-Phuong; Caberlotto, Laura

2016-12-01

The pathophysiological basis of major depression is incompletely understood. Recently, numerous proteomic studies have been performed in rodent models of depression to investigate the molecular underpinnings of depressive-like behaviours with an unbiased approach. The objective of the study is to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease. Network analysis is performed integrating preexisting proteomic data from rodent models of depression. The IntAct mouse and the HRPD are used as reference protein-protein interaction databases. The functionality analyses of the networks are then performed by testing overrepresented GO biological process terms and pathways. Functional enrichment analyses of the networks revealed an association with molecular processes related to depression in humans, such as those involved in the immune response. Pathways impacted by clinically effective antidepressants are modulated, including glutamatergic signaling and neurotrophic responses. Moreover, dysregulations of proteins regulating energy metabolism and circadian rhythms are implicated. The comparison with protein pathways modulated in depressive patients revealed significant overlapping. This systems biology study supports the notion that animal models can contribute to the research into the biology and therapeutics of depression. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

How many food additives are rodent carcinogens?

Science.gov (United States)

Johnson, F M

2002-01-01

One generally assumes that chemical agents added to foods are reasonably free of risks to human health, and practically everyone consumes some additives in his or her food daily throughout life. In the United States, the 1958 Food Additives Amendment to the Federal Food, Drug and Cosmetic Act of 1938 requires food manufacturers to demonstrate the safety of food additives to the Food and Drug Administration (FDA). The Amendment contains a provision that prohibits approval of an additive if it is found to cause cancer in humans or animals. In the present study, data from the National Toxicology Program rodent bioassay (NTPRB) were used to identify a sample of approximately 50 rodent-tested additives and other chemicals added to food that had been evaluated independently of the FDA/food industry. Surprisingly, the sample shows more than 40% of these food chemicals to be carcinogenic in one or more rodent groups. If this percentage is extrapolated to all substances added to food in the United States, it would imply that more than 1000 of such substances are potential rodent carcinogens. The NTP and FDA test guidelines use similar, though not necessarily identical, rodent test procedures, including near lifetime exposures to the maximum tolerated dose. The FDA specifies that test chemicals should be administered by the oral route. However, the oral route includes three methods of delivering chemicals, that is, mixed in the food or water or delivered by stomach tube (gavage). The NTP data show only 1 of 18 food chemicals mixed in the food are rodent carcinogens, but 16 of 23 gavage-administered food chemicals are carcinogenic to rodents. The distribution suggests that among orally delivered chemicals, those administered in the feed will more likely prove to be noncarcinogens than chemicals given by gavage. The rodent data also reveal that effects may vary according to dose and genotype, as well as by route of administration, to further complicate extrapolation to humans

Competitive release and facilitation of drug-resistant parasites after therapeutic chemotherapy in a rodent malaria model

Science.gov (United States)

Wargo, A.R.; Huijben, S.; De Roode, J. C.; Shepherd, J.; Read, A.F.

2007-01-01

Malaria infections frequently consist of mixtures of drug-resistant and drug-sensitive parasites. If crowding occurs, where clonal population densities are suppressed by the presence of coinfecting clones, removal of susceptible clones by drug treatment could allow resistant clones to expand into the newly vacated niche space within a host. Theoretical models show that, if such competitive release occurs, it can be a potent contributor to the strength of selection, greatly accelerating the rate at which resistance spreads in a population. A variety of correlational field data suggest that competitive release could occur in human malaria populations, but direct evidence cannot be ethically obtained from human infections. Here we show competitive release after pyrimethamine curative chemotherapy of acute infections of the rodent malaria Plasmodium chabaudi in laboratory mice. The expansion of resistant parasite numbers after treatment resulted in enhanced transmission-stage densities. After the elimination or near-elimination of sensitive parasites, the number of resistant parasites increased beyond that achieved when a competitor had never been present. Thus, a substantial competitive release occurred, markedly elevating the fitness advantages of drug resistance above those arising from survival alone. This finding may explain the rapid spread of drug resistance and the subsequently brief useful lifespans of some antimalarial drugs. In a second experiment, where subcurative chemotherapy was administered, the resistant clone was only partly released from competitive suppression and experienced a restriction in the size of its expansion after treatment. This finding raises the prospect of harnessing in-host ecology to slow the spread of drug resistance. ?? 2007 by The National Academy of Sciences of the USA.

Opportunities for improving animal welfare in rodent models of epilepsy and seizures.

Science.gov (United States)

Lidster, Katie; Jefferys, John G; Blümcke, Ingmar; Crunelli, Vincenzo; Flecknell, Paul; Frenguelli, Bruno G; Gray, William P; Kaminski, Rafal; Pitkänen, Asla; Ragan, Ian; Shah, Mala; Simonato, Michele; Trevelyan, Andrew; Volk, Holger; Walker, Matthew; Yates, Neil; Prescott, Mark J

2016-02-15

Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Conspecific Interactions in Adult Laboratory Rodents: Friends or Foes?

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Lukas, Michael; de Jong, Trynke R

2017-01-01

Interactions between adult conspecifics, including sexual behaviors, affiliation, and aggression are crucial for the well-being, survival, and reproduction of mammals. This holds true for any mammalian species, but certainly for humans: An inability to optimally navigate the social system can have a strong negative impact on physical and mental health. Translational rodent models have been used for decades to unravel the neural pathways and substrates involved in normal and abnormal conspecific interactions. Researchers in the field of translational social neuroscience face a double challenge: Not only do they need to pay considerable attention to the behavioral ecology of their model species or their ancestors, they also have to expect a relatively large variability in behavior and adjust their experimental design accordingly. In this chapter, we will lay out traditional and novel rodent models and paradigms to study sexual, affiliative, and aggressive interactions among adult conspecifics. We will discuss the merits and main findings and briefly consider the most promising novel directions. Finally, we review the modulatory involvement of two major players in mammal social interaction: the central oxytocin and vasopressin system.

Convergent and Divergent Adaptations of Subterranean Rodents

DEFF Research Database (Denmark)

Fang, Xiaodong

Subterranean rodents comprise approximately 250 species that spend their entire lives in underground, unventilated tunnels, distributed along all continents except Australia and Antarctica. Subterranean rodents escape from predators and extreme climatic fluctuations in their underground habitats,...

Methods for Dissecting Motivation and Related Psychological Processes in Rodents.

Science.gov (United States)

Ward, Ryan D

2016-01-01

Motivational impairments are increasingly recognized as being critical to functional deficits and decreased quality of life in patients diagnosed with psychiatric disease. Accordingly, much preclinical research has focused on identifying psychological and neurobiological processes which underlie motivation . Inferring motivation from changes in overt behavioural responding in animal models, however, is complicated, and care must be taken to ensure that the observed change is accurately characterized as a change in motivation , and not due to some other, task-related process. This chapter discusses current methods for assessing motivation and related psychological processes in rodents. Using an example from work characterizing the motivational impairments in an animal model of the negative symptoms of schizophrenia, we highlight the importance of careful and rigorous experimental dissection of motivation and the related psychological processes when characterizing motivational deficits in rodent models . We suggest that such work is critical to the successful translation of preclinical findings to therapeutic benefits for patients.

Rodent-borne diseases and their public health importance in Iran.

Directory of Open Access Journals (Sweden)

Mohammad Hasan Rabiee

2018-04-01

Full Text Available Rodents are reservoirs and hosts for several zoonotic diseases such as plague, leptospirosis, and leishmaniasis. Rapid development of industry and agriculture, as well as climate change throughout the globe, has led to change or increase in occurrence of rodent-borne diseases. Considering the distribution of rodents throughout Iran, the aim of this review is to assess the risk of rodent-borne diseases in Iran.We searched Google Scholar, PubMed, Science Direct, Scientific Information Database (SID, and Magiran databases up to September 2016 to obtain articles reporting occurrence of rodent-borne diseases in Iran and extract information from them. Out of 70 known rodent-borne diseases, 34 were reported in Iran: 17 (50% parasitic diseases, 13 (38% bacterial diseases, and 4 (12% viral diseases. Twenty-one out of 34 diseases were reported from both humans and rodents. Among the diseases reported in the rodents of Iran, plague, leishmaniasis, and hymenolepiasis were the most frequent. The most infected rodents were Rattus norvegicus (16 diseases, Mus musculus (14 diseases, Rattus rattus (13 diseases, Meriones persicus (7 diseases, Apodemus spp. (5 diseases, Tatera indica (4 diseases, Meriones libycus (3 diseases, Rhombomys opimus (3 diseases, Cricetulus migratorius (3 diseases, and Nesokia indica (2 diseases.The results of this review indicate the importance of rodent-borne diseases in Iran. Considering notable diversity of rodents and their extensive distribution throughout the country, it is crucial to pay more attention to their role in spreading infectious diseases for better control of the diseases.

Rodent-borne diseases and their public health importance in Iran

Science.gov (United States)

Mahmoudi, Ahmad; Siahsarvie, Roohollah; Kryštufek, Boris; Mostafavi, Ehsan

2018-01-01

Background Rodents are reservoirs and hosts for several zoonotic diseases such as plague, leptospirosis, and leishmaniasis. Rapid development of industry and agriculture, as well as climate change throughout the globe, has led to change or increase in occurrence of rodent-borne diseases. Considering the distribution of rodents throughout Iran, the aim of this review is to assess the risk of rodent-borne diseases in Iran. Methodology/Principal finding We searched Google Scholar, PubMed, Science Direct, Scientific Information Database (SID), and Magiran databases up to September 2016 to obtain articles reporting occurrence of rodent-borne diseases in Iran and extract information from them. Out of 70 known rodent-borne diseases, 34 were reported in Iran: 17 (50%) parasitic diseases, 13 (38%) bacterial diseases, and 4 (12%) viral diseases. Twenty-one out of 34 diseases were reported from both humans and rodents. Among the diseases reported in the rodents of Iran, plague, leishmaniasis, and hymenolepiasis were the most frequent. The most infected rodents were Rattus norvegicus (16 diseases), Mus musculus (14 diseases), Rattus rattus (13 diseases), Meriones persicus (7 diseases), Apodemus spp. (5 diseases), Tatera indica (4 diseases), Meriones libycus (3 diseases), Rhombomys opimus (3 diseases), Cricetulus migratorius (3 diseases), and Nesokia indica (2 diseases). Conclusions/Significance The results of this review indicate the importance of rodent-borne diseases in Iran. Considering notable diversity of rodents and their extensive distribution throughout the country, it is crucial to pay more attention to their role in spreading infectious diseases for better control of the diseases. PMID:29672510

Epidemiology of Leptospira Transmitted by Rodents in Southeast Asia

Science.gov (United States)

Mielcarek, Mathilde; Tatard, Caroline; Chaval, Yannick; Suputtamongkol, Yupin; Buchy, Philippe; Jittapalapong, Sathaporn; Herbreteau, Vincent; Morand, Serge

2014-01-01

Background Leptospirosis is the most common bacterial zoonoses and has been identified as an important emerging global public health problem in Southeast Asia. Rodents are important reservoirs for human leptospirosis, but epidemiological data is lacking. Methodology/Principal Findings We sampled rodents living in different habitats from seven localities distributed across Southeast Asia (Thailand, Lao PDR and Cambodia), between 2009 to 2010. Human isolates were also obtained from localities close to where rodents were sampled. The prevalence of Leptospira infection was assessed by real-time PCR using DNA extracted from rodent kidneys, targeting the lipL32 gene. Sequencing rrs and secY genes, and Multi Locus Variable-number Tandem Repeat (VNTR) analyses were performed on DNA extracted from rat kidneys for Leptospira isolates molecular typing. Four species were detected in rodents, L. borgpetersenii (56% of positive samples), L. interrogans (36%), L. kirschneri (3%) and L. weilli (2%), which were identical to human isolates. Mean prevalence in rodents was approximately 7%, and largely varied across localities and habitats, but not between rodent species. The two most abundant Leptospira species displayed different habitat requirements: L. interrogans was linked to humid habitats (rice fields and forests) while L. borgpetersenii was abundant in both humid and dry habitats (non-floodable lands). Conclusion/Significance L. interrogans and L. borgpetersenii species are widely distributed amongst rodent populations, and strain typing confirmed rodents as reservoirs for human leptospirosis. Differences in habitat requirements for L. interrogans and L. borgpetersenii supported differential transmission modes. In Southeast Asia, human infection risk is not only restricted to activities taking place in wetlands and rice fields as is commonly accepted, but should also include tasks such as forestry work, as well as the hunting and preparation of rodents for consumption, which

Ectoparasites of Rodents Captured in Hamedan, Western Iran

Directory of Open Access Journals (Sweden)

Hamid Zendehfili

2015-10-01

Full Text Available Background: Rodents with a population greater than the entire population of other mammals on earth are the source of economic losses and health conflicts. One of the major health problems with the rodents is their role as reservoir hosts of zoonotic diseases. The aim of this study was to assess the infestation of commensal rodents with ectoparasites in Hamedan City, Western Iran.Methods: The samples were collected by live traps during years 2012–2013. After transferring the samples to the Entomological Laboratory of Hamedan University of Medical Sciences, their ectoparasites were collected andidentified.Results: A total of 171 slides were prepared from 105 captured commensal rodents: Mus musculus, Rattus rattus and R. norvegicus comprising three orders namely Mesostigmata: Hypoaspis (Laelaspis astronomica, Dermanyssius sp, Pachylaelapidae (male. Metastigmata: Rhipicephalus sp and Anoplura: Polyplax spinulosa were recovered in Hamedan City. Seventy (66.6% rodents were found infested with at least one species of ectoparasites.Conclusion: The results of our study indicate that ectoparasites infestation in commensal rodents of Hamedan city is high and more attention by local health authorities is needed to prevent zoonotic diseases.

A unique rodent model of cardiometabolic risk associated with the metabolic syndrome and polycystic ovary syndrome.

Science.gov (United States)

Shi, Danni; Dyck, Michael K; Uwiera, Richard R E; Russell, Jim C; Proctor, Spencer D; Vine, Donna F

2009-09-01

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-/anovulation, and polycystic ovarian morphology and is a complex endocrine disorder that also presents with features of the metabolic syndrome, including obesity, insulin resistance, and dyslipidemia. These latter symptoms form cardiometabolic risk factors predisposing individuals to the development of type 2 diabetes and cardiovascular disease (CVD). To date, animal models to study PCOS in the context of the metabolic syndrome and CVD risk have been lacking. The aim of this study was to investigate the JCR:LA-cp rodent as an animal model of PCOS associated with the metabolic syndrome. Metabolic indices were measured at 6 and 12 wk, and reproductive parameters including ovarian morphology and estrous cyclicity were assessed at 12 wk or adulthood. At 6 wk of age, the cp/cp genotype of the JCR:LA-cp strain developed visceral obesity, insulin resistance, and dyslipidemia (hypertriglyceridemia and hypercholesterolemia) compared with control animals. Serum testosterone concentrations were not significantly different between groups at 6 wk of age. However, at 12 wk, the cp/cp genotype had higher serum testosterone concentrations, compared with control animals, and presented with oligoovulation, a decreased number of corpora lutea, and an increased number of total follicles, in particular atretic and cystic follicles. The cardiometabolic risk factors in the cp/cp animals were exacerbated at 12 wk including obesity, insulin resistance, and dyslipidemia. The results of this study demonstrate that the JCR:LA-cp rodent may be a useful PCOS-like model to study early mechanisms involved in the etiology of cardiometabolic risk factors in the context of both PCOS and the metabolic syndrome.

A Community-Based Surveillance on Determinants of Rodent Infestation

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Hsiu-Hua Pai

2003-01-01

Full Text Available Rodent infestation is an important factor in the transmission of infectious diseases of public health importance. From October to November 1998, surveillance stations were established in 110 boroughs of Kaohsiung City in southern Taiwan. Boroughs were chosen by random sampling 10 boroughs from each of 11 districts (464 boroughs in the city. The extent of rodent infestation was determined by cage trapping. The possibility of applying a community-based control program was evaluated by investigating associated demographic and environmental factors as well as related knowledge, attitudes, and behaviors. A total of 90 rodents were trapped in 41% of the 110 boroughs. Using univariate analyses, 17 factors were significantly associated with rodent infestation. A lack of knowledge that rodent control relies on community cooperation was the most important factor among the seven variables associated with the extent of rodent infestation (OR 3.1 by logistic multiple regression. This revealed the importance of community cooperation in controlling rodent infestation. Moreover, improvement of environmental hygiene associated with garbage problems, such as cleanliness of storage rooms and closets, and the hygiene of empty space and resource recycling stations should not be ignored.

Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure

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This paper shows that rat models of cardiovascular diseases have differential degrees of underlying pathologies at a young age. Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. How...

Abnormal stress responsivity in a rodent developmental disruption model of schizophrenia.

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Zimmerman, Eric C; Bellaire, Mark; Ewing, Samuel G; Grace, Anthony A

2013-10-01

Although numerous studies have implicated stress in the pathophysiology of schizophrenia, less is known about how the effects of stress interact with genetic, developmental, and/or environmental determinants to promote disease progression. In particular, it has been proposed that in humans, stress exposure in adolescence could combine with a predisposition towards increased stress sensitivity, leading to prodromal symptoms and eventually psychosis. However, the neurobiological substrates for this interaction are not fully characterized. Previous work in our lab has demonstrated that rats born to dams administered with the DNA-methylating agent methylazoxymethanol acetate (MAM) at gestational day 17 exhibit as adults behavioral and anatomical abnormalities consistent with those observed in patients with schizophrenia. Here, we examined behavioral and neuroendocrine responses to stress in the MAM model of schizophrenia. MAM-treated male rats were exposed to acute and repeated footshock stress at prepubertal, peripubteral, and adult ages. Ultrasonic vocalizations (USVs), freezing, and corticosterone responses were quantified. We found that juvenile MAM-treated rats emitted significantly more calls, spent more time vocalizing, emitted calls at a higher rate, and showed more freezing in response to acute footshock stress when compared with their saline (SAL) treated counterparts, and that this difference is not present in older animals. In addition, adolescent MAM-treated animals displayed a blunted HPA axis corticosterone response to acute footshock that did not adapt after 10 days of stress exposure. These data demonstrate abnormal stress responsivity in the MAM model of schizophrenia and suggest that these animals are more sensitive to the effects of stress in youth.

A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents

DEFF Research Database (Denmark)

Finan, Brian; Yang, Bin; Ottaway, Nickki

2015-01-01

-in-class monoagonists to reduce body weight, enhance glycemic control and reverse hepatic steatosis in relevant rodent models. Various loss-of-function models, including genetic knockout, pharmacological blockade and selective chemical knockout, confirmed contributions of each constituent activity in vivo. We...

Cardiometabolic and reproductive benefits of early dietary energy restriction and voluntary exercise in an obese PCOS-prone rodent model.

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Diane, Abdoulaye; Kupreeva, Maria; Borthwick, Faye; Proctor, Spencer D; Pierce, W David; Vine, Donna F

2015-09-01

Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age characterized by ovulatory dysfunction, hyperandrogenism and cardiometabolic risk. The overweight-obese PCOS phenotype appears to have exacerbated reproductive dysfunction and cardiometabolic risk. In overweight-obese adult women with PCOS, exercise and energy restricted diets have shown limited and inconsistent effects on both cardiometabolic indices and reproductive outcomes. We hypothesized that an early lifestyle intervention involving exercise and dietary energy restriction to prevent or reduce the propensity for adiposity would modulate reproductive indices and cardiometabolic risk in an obese PCOS-prone rodent model. Weanling obese PCOS-prone and Lean-Control JCR:LA-cp rodents were given a chow diet ad libitum or an energy-restricted diet combined with or without voluntary exercise (4  h/day) for 8 weeks. Dietary energy restriction and exercise lowered total body weight gain and body fat mass by 30% compared to free-fed sedentary or exercising obese PCOS-prone animals (Pexercise intensity compared to free-feeding plus exercise conditions. Energy restriction and exercise decreased fasting plasma triglycerides and apoB48 concentrations in obese PCOS-prone animals compared to free-fed and exercise or sedentary groups. The energy restriction and exercise combination in obese PCOS-prone animals significantly increased plasma sex-hormone binding globulin, hypothalamic cocaine-and amphetamine-regulated transcript (CART) and Kisspeptin mRNA expression to levels of the Lean-Control group, and this was further associated with improvements in estrous cyclicity. The combination of exercise and dietary energy restriction when initiated in early life exerts beneficial effects on cardiometabolic and reproductive indices in an obese PCOS-prone rodent model, and this may be associated with normalization of the hypothalamic neuropeptides, Kisspeptin and CART

Intestinal tumorigenesis is not affected by progesterone signaling in rodent models.

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Jarom Heijmans

Full Text Available Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR is not expressed. Expression was confined to sporadic mesenchymal cells. To analyze the influence of systemic progesterone receptor signaling, we crossed mice that lacked the progesterone receptor (PRKO to the Apc(Min/+ mouse, a model for spontaneous intestinal polyposis. PRKO-Apc(Min/+ mice exhibited no change in polyp number, size or localization compared to Apc(Min/+. To examine effects of progestins on the intestinal epithelium that are independent of the PR, we treated mice with MPA. We found no effects of either progesterone or MPA on gross intestinal morphology or epithelial proliferation. Also, in rats treated with MPA, injection with the carcinogen azoxymethane did not result in a difference in the number or size of aberrant crypt foci, a surrogate end-point for adenoma development. We conclude that expression of the progesterone receptor is limited to cells in the intestinal mesenchyme. We did not observe any effect of progesterone receptor signaling or of progestin treatment in rodent models of intestinal tumorigenesis.

Hunting, Food Preparation, and Consumption of Rodents in Lao PDR.

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Kanokwan Suwannarong

Full Text Available A cross-sectional study was conducted in 29 villages of Khamkeuth District in Bolikhamxay Province in the Lao PDR during March to May 2013. The study aimed to determine the characteristics associated with rodent consumption and related behaviors among different ethnic groups, ages, and genders. Five-hundred-eighty-four (584 males and females from 18-50 years of age participated in this study. Half of them were Hmong (292, 50% while 152 respondents were Lao-Tai (26% or other ethnic groups (140, 24%. Most of the respondents (79.5% had farming as their main occupation. Prevalences of the studied outcomes were high: 39.9 for hunting or capturing rodents in the previous year, 77.7% for preparing rodents as food, and 86.3% for rodent consumption. Multivariable logistic regression analysis showed that likelihood of these types of rodent contact was more consistently associated with behavioral factors (gathering things from the forest and elsewhere, cultivation-related activities, and taking measures to prevent rodent-borne disease than with socio-demographic, environmental, or cultural factors. The strongest associations were observed for gathering things; these associations were consistently positive and statistically significant. Although this study did not directly assess rodent-borne zoonosis risk, we believe that study findings raise concern that such risk may be substantial in the study area and other similar areas. Further epidemiological studies on the association between rodent-borne disease infection and rodent hunting, preparation for food, and consumption are recommended. Moreover, further studies are needed on the association between these potential exposure factors (i.e., rodent hunting, preparation for food, and consumption and rodent-borne infections, especially among ethnic groups like the Hmong in Lao PDR and those in neighboring countries with similar socio-demographic, environmental, behavioral and cultural contexts.

Subcutaneous oxyntomodulin analogue administration reduces body weight in lean and obese rodents.

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Liu, Y-L; Ford, H E; Druce, M R; Minnion, J S; Field, B C T; Shillito, J C; Baxter, J; Murphy, K G; Ghatei, M A; Bloom, S R

2010-12-01

To determine the efficacy of a long-acting oxyntomodulin (OXM) analogue, OXM6421, in inhibiting food intake and decreasing body weight in lean and diet-induced obese (DIO) rodents. The glucagon-like peptide-1 (GLP-1) receptor binding affinity and efficacy, sensitivity to enzymatic degradation in vitro and persistence in the circulation after peripheral administration were investigated for OXM6421 and compared with native OXM. The chronic effect of OXM6421 on food intake, body weight and energy expenditure was examined in lean rats, and its anti-obesity potential was evaluated in DIO mice. OXM6421 showed enhanced GLP-1 receptor binding affinity and cyclic adenosine monophosphate (cAMP) stimulation, and higher resistance to enzymatic degradation by dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidase (NEP) compared with native OXM. OXM6421 persisted longer in the circulation than OXM after peripheral administration. Acute administration of OXM6421 potently inhibited food intake in lean rodents, with cumulative effects lasting up to 24 h. In lean rats, daily subcutaneous (s.c.) administration of OXM6421 caused greater weight loss than the pair-fed animals, and a higher rate of oxygen consumption than both the pair-fed and the saline controls. In DIO mice, continuous s.c. infusion of OXM6421 resulted in a significant weight loss, accompanied by an improvement in glucose homeostasis and an increase in circulating adiponectin levels. Once-daily s.c. administration of OXM6421 for 21 days caused sustained weight loss in DIO mice. OXM6421 induces negative energy balance in both lean and obese rodents, suggesting that long-acting OXM analogues may represent a potential therapy for obesity.

Dietary patterns of two herbivorous rodents: and Parotomys brantsii ...

African Journals Online (AJOL)

Frequency of occurrence of plant species in the diets were compared with availability of the plants in the rodents' habitats. Both rodents are generalist herbivores, eating plants species in proportion to the availability in their habitats. Dietary patterns, diversity of diet and degree of overlap between rodent's diets are a function ...

Thermoregulation of the subterranean rodent genus Bathyergus ...

African Journals Online (AJOL)

The thermoregulation of the largest subterranean rodent, genus Bathyergus, comprising two species, B. suillus and B. janetta,occurring in mesic and semiarid habitats respectively, was investigated and compared with that of other subterranean rodents. Both species display low resting metabolic rates and low body ...

A Field Study of Plague and Tularemia in Rodents, Western Iran.

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Mostafavi, Ehsan; Shahraki, Abdolrazagh Hashemi; Japoni-Nejad, Alireza; Esmaeili, Saber; Darvish, Jamshid; Sedaghat, Mohammad Mehdi; Mohammadi, Ali; Mohammadi, Zeinolabedin; Mahmoudi, Ahmad; Pourhossein, Behzad; Ghasemi, Ahmad; Gyuranecz, Miklós; Carniel, Elisabeth

2017-04-01

Kurdistan Province in Iran is a historical focus for plague and tularemia. This study aimed at assessing the current status of these two foci by studying their rodent reservoirs. Rodents were trapped and their ectoparasites were collected. The genus and species of both rodents and ectoparasites were determined. Serological analyses of rodent blood samples were done by enzyme-linked immunosorbent assay for plague and by standard tube agglutination assay for tularemia. Rodent spleen samples were subjected to bacterial culture, microscopic examination, and real-time PCR to search for active plague or tularemia infection. During this study, 245 rodents were trapped, of which the most abundant genera were Apodemus (40%), Mus (24.49%), and Meriones (12.65%). One hundred fifty-three fleas, 37 mites, and 54 ticks were collected on these rodents. The results of all direct and indirect tests were negative for plague. Serological tests were positive for tularemia in 4.8% of trapped rodents. This study is the first report on the presence of tularemia infection in rodents in Western Iran. Since Meriones persicus is a known reservoir for plague and tularemia, and this rodent carried plague and tularemia vectors in Marivan and Sanandaj districts, there is a real potential for the occurrence of these two diseases in this region.

Essential role of transient receptor potential M8 (TRPM8) in a model of acute cold-induced urinary urgency.

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Uvin, Pieter; Franken, Jan; Pinto, Silvia; Rietjens, Roma; Grammet, Luc; Deruyver, Yves; Alpizar, Yeranddy A; Talavera, Karel; Vennekens, Rudi; Everaerts, Wouter; De Ridder, Dirk; Voets, Thomas

2015-10-01

Acute exposure of part of the skin to cold stimuli can evoke urinary urgency, a phenomenon termed acute cold-induced urgency (ACIU). Despite its high prevalence, particularly in patients with overactive bladder, little is known about the mechanisms that induce ACIU. To develop an animal model of ACIU and test the involvement of cold-activated ion channels transient receptor potential (TRP) M8 and TRPA1. Intravesical pressure and micturition were monitored in female mice (wild-type C57BL/6J, Trpa1(-/-), Trpm8(+/+), and Trpm8(-/-)) and Sprague Dawley rats. An intravesical catheter was implanted. Localized cooling of the skin was achieved using a stream of air or topical acetone. The TRPM8 antagonist (N-(3-aminopropyl)-2-{[(3-methylphenyl) methyl]oxy}-N-(2-thienylmethyl)benzamide (AMTB) or vehicle was injected intraperitoneally. Frequencies of bladder contractions and voids in response to sensory stimuli were compared using the Mann-Whitney or Kruskal-Wallis test. Brief, innocuously cold stimuli applied to different parts of the skin evoked rapid bladder contractions and voids in anesthetized mice and rats. These responses were strongly attenuated in Trpm8(-/-) mice and in rats treated with AMTB. As rodent bladder physiology differs from that of humans, it is difficult to directly extrapolate our findings to human patients. Our findings indicate that ACIU is an evolutionarily conserved reflex rather than subconscious conditioning, and provide a useful in vivo model for further investigation of the underlying mechanisms. Pharmacological inhibition of TRPM8 may be useful for treating ACIU symptoms in patients. Brief cold stimuli applied to the skin can evoke a sudden desire to urinate, which can be highly bothersome in patients with overactive bladder. We developed an animal model to study this phenomenon, and found that it depends on a specific molecular cold sensor, transient receptor potential M8 (TRPM8). Pharmacological inhibition of TRPM8 may alleviate acute cold

Effects of glyphosate exposure on sperm concentration in rodents: A systematic review and meta-analysis.

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Cai, Wenyan; Ji, Ying; Song, Xianping; Guo, Haoran; Han, Lei; Zhang, Feng; Liu, Xin; Zhang, Hengdong; Zhu, Baoli; Xu, Ming

2017-10-01

Correlation between exposure to glyphosate and sperm concentrations is important in reproductive toxicity risk assessment for male reproductive functions. Many studies have focused on reproductive toxicity on glyphosate, however, results are still controversial. We conducted a systematic review of epidemiological studies on the association between glyphosate exposure and sperm concentrations of rodents. The aim of this study is to explore the potential adverse effects of glyphosate on reproductive function of male rodents. Systematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Embase, WANFANG and CNKI databases with different combinations of glyphosate exposure and sperm concentration. 8 studies were eventually identified and random-effect model was conducted. Heterogeneity among study results was calculated via chi-square tests. Ten independent experimental datasets from these eight studies were acquired to synthesize the random-effect model. A decrease in sperm concentrations was found with mean difference of sperm concentrations(MDsperm)=-2.774×10 6 /sperm/g/testis(95%CI=-0.969 to -4.579) in random-effect model after glyphosate exposure. There was also a significant decrease after fitting the random-effect model: MDsperm=-1.632×10 6 /sperm/g/testis (95%CI=-0.662 to -2.601). The results of meta-analysis support the hypothesis that glyphosate exposure decreased sperm concentration in rodents. Therefore, we conclude that glyphosate is toxic to male rodent's reproductive system. Copyright © 2017. Published by Elsevier B.V.

Uus Multiphonic Rodent

Index Scriptorium Estoniae

2009-01-01

Tartus tegutsenud eksperimentaal-rock-duo Opium Flirt Eestisse jäänud liige Erki Hõbe (paarimees Ervin Trofimov tegutseb Ungaris) annab välja oma teise sooloalbumi nime all Multiphonic Rodent, heliplaadi "Astral Dance" esitluskontsert toimub 5. veebruaril Tallinnas baaris Juuksur

A Theoretical and Experimental Investigation of Mechanical Damage to Rodent Sperm Generated by Microscale Ice Formation.

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Han, X; Critser, J K

　　BACKGROUND: Rodent sperm cryopreservation is of critical importance for the maintenance of lines or strains of genetically engineered mice and rats. However, rodent sperm are extremely mechanically sensitive due to their unusual morphology, and are severely damaged using current methods of cryopreservation. Those methods result in poor post thaw motility (PTM) for mouse. To investigate the mechanism of mechanical damage introduced to rodent sperm during freezing, a micro-mechanical model was established to analyze the sperm radial and axial thermal stresses generated by microscale extracellular ice formation. PTM of mouse sperm cryopreserved in capillaries of different radii (100, 200, 344, 526, 775µm) was measured using a standard computer-assisted sperm analysis system. The model predicts that when one of the inner dimensions of the containers (the inner diameter of plastic straws or straw capillaries) is on the same order of magnitude of sperm length, axial stress is significantly increased. The experimental results showed that the value of PTM was decreased from 38 ± 8 % in the larger (775µm) capillaries to 0 ± 0 % in the smaller (100 µm) ones. Theoretical analysis based on the established model were experimentally validated and can be used to guide the design of novel devices to improve the efficiency of rodent sperm cryopreservation.

Exploring acute-to-chronic neuropathic pain in rats after contusion spinal cord injury.

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Gaudet, Andrew D; Ayala, Monica T; Schleicher, Wolfgang E; Smith, Elana J; Bateman, Emily M; Maier, Steven F; Watkins, Linda R

2017-09-01

Spinal cord injury (SCI) causes chronic pain in 65% of individuals. Unfortunately, current pain management is inadequate for many SCI patients. Rodent models could help identify how SCI pain develops, explore new treatment strategies, and reveal whether acute post-SCI morphine worsens chronic pain. However, few studies explore or compare SCI-elicited neuropathic pain in rats. Here, we sought to determine how different clinically relevant contusion SCIs in male and female rats affect neuropathic pain, and whether acute morphine worsens later chronic SCI pain. First, female rats received sham surgery, or 150kDyn or 200kDyn midline T9 contusion SCI. These rats displayed modest mechanical allodynia and long-lasting thermal hyperalgesia. Next, a 150kDyn (1s dwell) midline contusion SCI was performed in male and female rats. Interestingly, males, but not females showed SCI-elicited mechanical allodynia; rats of both sexes had thermal hyperalgesia. In this model, acute morphine treatment had no significant effect on chronic neuropathic pain symptoms. Unilateral SCIs can also elicit neuropathic pain that could be exacerbated by morphine, so male rats received unilateral T13 contusion SCI (100kDyn). These rats exhibited significant, transient mechanical allodynia, but not thermal hyperalgesia. Acute morphine did not exacerbate chronic pain. Our data show that specific rat contusion SCI models cause neuropathic pain. Further, chronic neuropathic pain elicited by these contusion SCIs was not amplified by our course of early post-trauma morphine. Using clinically relevant rat models of SCI could help identify novel pain management strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

Aging models of acute seizures and epilepsy.

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Kelly, Kevin M

2010-01-01

Aged animals have been used by researchers to better understand the differences between the young and the aged brain and how these differences may provide insight into the mechanisms of acute seizures and epilepsy in the elderly. To date, there have been relatively few studies dedicated to the modeling of acute seizures and epilepsy in aged, healthy animals. Inherent challenges to this area of research include the costs associated with the purchase and maintenance of older animals and, at times, the unexpected and potentially confounding comorbidities associated with aging. However, recent studies using a variety of in vivo and in vitro models of acute seizures and epilepsy in mice and rats have built upon early investigations in the field, all of which has provided an expanded vision of seizure generation and epileptogenesis in the aged brain. Results of these studies could potentially translate to new and tailored interventional approaches that limit or prevent the development of epilepsy in the elderly.

Assessment of the Effects of Acute and Repeated Exposure to Blast Overpressure in Rodents: Towards a Greater Understanding of Blast and the Potential Ramifications for Injury in Humans Exposed to Blast

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Stephen Thomas Ahlers

2012-03-01

Full Text Available Mild traumatic brain injury (mTBI resulting from exposure to improvised explosive devices (IEDs has fueled a requirement to develop animals models that mirror this condition using exposure to blast overpressure (BOP. En route to developing a model of repeated exposure to BOP we sought to initially characterize the effects of acute BOP exposure in rodents, focusing specifically on the levels of BOP exposure that produced clinical mTBI symptoms. We first measured BOP effects on gross motor function on a balance beam. Separate groups of unanesthetized rats were exposed (in different orientations to 40 kPa, 75 kPa and 120 kPa BOP exposure inside a pneumatically driven shock tube. Results demonstrated that rats exposed to 120 kPa demonstrated transient alterations or loss of consciousness indicated by a transient loss of righting and by increased latencies on the balance beam. The 120 kPa exposure was the threshold for overt pathology for acute BOP exposure with approximately 30% of rats presenting with evidence of subdural hemorrhage and cortical contusions. All animals exposed to 120 kPa BOP manifested evidence of significant pulmonary hemorrhage. Anterograde memory deficits were observed in rats exposed to 75 kPa facing the BOP wave and rats exposed to 120 kPa in the lateral (side orientation. We next assessed repeated exposure to either lateral or frontal 40 kPa BOP in anesthetized rats, once per day for 12 days. Results showed that repeated exposure in the frontal, but not side, orientation to the BOP wave produced a transitory learning deficit on a Morris water maze (MWM task as shown by significantly longer latencies to reach the submerged platform in the second and third blocks of a four block session. Implications of these data are discussed in relation to the manifestation of mTBI in military personnel exposed to IEDs. Finally, we suggest that there are multiple types of brain injury from blast.

Rodent management: the man/environment interface

International Nuclear Information System (INIS)

Jackson, W.B.

1978-01-01

Rodents which interact with man generally are regarded as undesirable. Attempts at eliminating such rodents by increasing predation (including traps, microbiological agents, toxicants) have been relatively unsuccessful. Management by environmental manipulation must be basic. This then can be supplemented with predation at critical points where public health, use practices, or imperfections in the system demand. Society mores, practices, and economic considerations also have significant impact on the management system

Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species

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Semple, Bridgette D.; Blomgren, Klas; Gimlin, Kayleen; Ferriero, Donna M.; Noble-Haeusslein, Linda J.

2013-01-01

Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using rodents of different ages have been developed, species differences in the timing of key brain maturation events can render comparisons of vulnerability and regenerative capacities difficult to interpret. Traditional models of developmental brain injury have utilized rodents at postnatal day 7–10 as being roughly equivalent to a term human infant, based historically on the measurement of post-mortem brain weights during the 1970s. Here we will examine fundamental brain development processes that occur in both rodents and humans, to delineate a comparable time course of postnatal brain development across species. We consider the timing of neurogenesis, synaptogenesis, gliogenesis, oligodendrocyte maturation and age-dependent behaviors that coincide with developmentally regulated molecular and biochemical changes. In general, while the time scale is considerably different, the sequence of key events in brain maturation is largely consistent between humans and rodents. Further, there are distinct parallels in regional vulnerability as well as functional consequences in response to brain injuries. With a focus on developmental hypoxicischemic encephalopathy and traumatic brain injury, this review offers guidelines for researchers when considering the most appropriate rodent age for the developmental stage or process of interest to approximate human brain development. PMID:23583307

Human models of acute lung injury

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Alastair G. Proudfoot

2011-03-01

Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

Global and 3D spatial assessment of neuroinflammation in rodent models of Multiple Sclerosis.

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Shashank Gupta

Full Text Available Multiple Sclerosis (MS is a progressive autoimmune inflammatory and demyelinating disease of the central nervous system (CNS. T cells play a key role in the progression of neuroinflammation in MS and also in the experimental autoimmune encephalomyelitis (EAE animal models for the disease. A technology for quantitative and 3 dimensional (3D spatial assessment of inflammation in this and other CNS inflammatory conditions is much needed. Here we present a procedure for 3D spatial assessment and global quantification of the development of neuroinflammation based on Optical Projection Tomography (OPT. Applying this approach to the analysis of rodent models of MS, we provide global quantitative data of the major inflammatory component as a function of the clinical course. Our data demonstrates a strong correlation between the development and progression of neuroinflammation and clinical disease in several mouse and a rat model of MS refining the information regarding the spatial dynamics of the inflammatory component in EAE. This method provides a powerful tool to investigate the effect of environmental and genetic forces and for assessing the therapeutic effects of drug therapy in animal models of MS and other neuroinflammatory/neurodegenerative disorders.

Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice.

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Buckman, Laura B; Thompson, Misty M; Lippert, Rachel N; Blackwell, Timothy S; Yull, Fiona E; Ellacott, Kate L J

2015-01-01

Introduction of a high-fat diet to mice results in a period of voracious feeding, known as hyperphagia, before homeostatic mechanisms prevail to restore energy intake to an isocaloric level. Acute high-fat diet hyperphagia induces astrocyte activation in the rodent hypothalamus, suggesting a potential role of these cells in the homeostatic response to the diet. The objective of this study was to determine physiologic role of astrocytes in the acute homeostatic response to high-fat feeding. We bred a transgenic mouse model with doxycycline-inducible inhibition of NFkappaB (NFκB) signaling in astrocytes to determine the effect of loss of NFκB-mediated astrocyte activation on acute high-fat hyperphagia. ELISA was used to measure the levels of markers of astrocyte activation, glial-fibrillary acidic protein (GFAP) and S100B, in the medial basal hypothalamus. Inhibition of NFκB signaling in astrocytes prevented acute high-fat diet-induced astrocyte activation and resulted in a 15% increase in caloric intake (P fat feeding.

Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa.

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Chowdhury, Tara Gunkali; Chen, Yi-Wen; Aoki, Chiye

2015-10-22

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A challenging illness to treat, due to the lack of understanding of the underlying neurobiology, AN has the highest mortality rate among psychiatric illnesses. To address this need, neuroscientists are using an animal model to study how neural circuits may contribute toward vulnerability to AN and may be affected by AN. Activity-based anorexia (ABA) is a bio-behavioral phenomenon described in rodents that models the key symptoms of anorexia nervosa. When rodents with free access to voluntary exercise on a running wheel experience food restriction, they become hyperactive - running more than animals with free access to food. Here, we describe the procedures by which ABA is induced in adolescent female C57BL/6 mice. On postnatal day 36 (P36), the animal is housed with access to voluntary exercise on a running wheel. After 4 days of acclimation to the running wheel, on P40, all food is removed from the cage. For the next 3 days, food is returned to the cage (allowing animals free food access) for 2 hr daily. After the fourth day of food restriction, free access to food is returned and the running wheel is removed from the cage to allow the animals to recover. Continuous multi-day analysis of running wheel activity shows that mice become hyperactive within 24 hr following the onset of food restriction. The mice run even during the limited time during which they have access to food. Additionally, the circadian pattern of wheel running becomes disrupted by the experience of food restriction. We have been able to correlate neurobiological changes with various aspects of the animals' wheel running behavior to implicate particular brain regions and neurochemical changes with resilience and vulnerability to food-restriction induced hyperactivity.

Can a native rodent species limit the invasive potential of a non-native rodent species in tropical agroforest habitats?

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Stuart, Alexander M; Prescott, Colin V; Singleton, Grant R

2016-06-01

Little is known about native and non-native rodent species interactions in complex tropical agroecosystems. We hypothesised that the native non-pest rodent Rattus everetti may be competitively dominant over the invasive pest rodent Rattus tanezumi within agroforests. We tested this experimentally by using pulse removal for three consecutive months to reduce populations of R. everetti in agroforest habitat, and assessed over 6 months the response of R. tanezumi and other rodent species. Following removal, R. everetti individuals rapidly immigrated into removal sites. At the end of the study period, R. tanezumi were larger and there was a significant shift in their microhabitat use with respect to the use of ground vegetation cover following the perturbation of R. everetti. Irrespective of treatment, R. tanezumi selected microhabitat with less tree canopy cover, indicative of severely disturbed habitat, whereas R. everetti selected microhabitat with a dense canopy. Our results suggest that sustained habitat disturbance in agroforests favours R. tanezumi, while the regeneration of agroforests towards a more natural state would favour native species and may reduce pest pressure in adjacent crops. In addition, the rapid recolonisation of R. everetti suggests this species would be able to recover from non-target impacts of short-term rodent pest control. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Calorie restriction in rodents: Caveats to consider.

Science.gov (United States)

Ingram, Donald K; de Cabo, Rafael

2017-10-01

The calorie restriction paradigm has provided one of the most widely used and most useful tools for investigating mechanisms of aging and longevity. By far, rodent models have been employed most often in these endeavors. Over decades of investigation, claims have been made that the paradigm produces the most robust demonstration that aging is malleable. In the current review of the rodent literature, we present arguments that question the robustness of the paradigm to increase lifespan and healthspan. Specifically, there are several questions to consider as follows: (1) At what age does CR no longer produce benefits? (2) Does CR attenuate cognitive decline? (3) Are there negative effects of CR, including effects on bone health, wound healing, and response to infection? (4) How important is schedule of feeding? (5) How long does CR need to be imposed to be effective? (6) How do genotype and gender influence CR? (7) What role does dietary composition play? Consideration of these questions produce many caveats that should guide future investigations to move the field forward. Published by Elsevier B.V.

Rodent model for assessing the long term safety and performance of peripheral nerve recording electrodes

Science.gov (United States)

Vasudevan, Srikanth; Patel, Kunal; Welle, Cristin

2017-02-01

Objective. In the US alone, there are approximately 185 000 cases of limb amputation annually, which can reduce the quality of life for those individuals. Current prosthesis technology could be improved by access to signals from the nervous system for intuitive prosthesis control. After amputation, residual peripheral nerves continue to convey motor signals and electrical stimulation of these nerves can elicit sensory percepts. However, current technology for extracting information directly from peripheral nerves has limited chronic reliability, and novel approaches must be vetted to ensure safe long-term use. The present study aims to optimize methods to establish a test platform using rodent model to assess the long term safety and performance of electrode interfaces implanted in the peripheral nerves. Approach. Floating Microelectrode Arrays (FMA, Microprobes for Life Sciences) were implanted into the rodent sciatic nerve. Weekly in vivo recordings and impedance measurements were performed in animals to assess performance and physical integrity of electrodes. Motor (walking track analysis) and sensory (Von Frey) function tests were used to assess change in nerve function due to the implant. Following the terminal recording session, the nerve was explanted and the health of axons, myelin and surrounding tissues were assessed using immunohistochemistry (IHC). The explanted electrodes were visualized under high magnification using scanning electrode microscopy (SEM) to observe any physical damage. Main results. Recordings of axonal action potentials demonstrated notable session-to-session variability. Impedance of the electrodes increased upon implantation and displayed relative stability until electrode failure. Initial deficits in motor function recovered by 2 weeks, while sensory deficits persisted through 6 weeks of assessment. The primary cause of failure was identified as lead wire breakage in all of animals. IHC indicated myelinated and unmyelinated axons

Testing the limits of Rodent Sperm Analysis: azoospermia in an otherwise healthy wild rodent population.

Science.gov (United States)

Tannenbaum, Lawrence V; Thran, Brandolyn H; Willams, Keith J

2009-01-01

By comparing the sperm parameters of small rodents trapped at contaminated terrestrial sites and nearby habitat-matched noncontaminated locations, the patent-pending Rodent Sperm Analysis (RSA) method provides a direct health status appraisal for the maximally chemical-exposed mammalian ecological receptor in the wild. RSA outcomes have consistently allowed for as definitive determinations of receptor health as are possible at the present time, thereby streamlining the ecological risk assessment (ERA) process. Here, we describe the unanticipated discovery, at a contaminated US EPA Superfund National Priorities List site, of a population of Hispid cotton rats (Sigmodon hispidus), with a high percentage of adult males lacking sperm entirely (azoospermia). In light of the RSA method's role in streamlining ERAs and in bringing contaminated Superfund-type site investigations to closure, we consider the consequences of the discovery. The two matters specifically discussed are (1) the computation of a population's average sperm count where azoospermia is present and (2) the merits of the RSA method and its sperm parameter thresholds-for-effect when azoospermia is masked in an otherwise apparently healthy rodent population.

Forecasting rodent outbreaks in Africa

DEFF Research Database (Denmark)

Leirs, Herwig; Verhagen, Ron; Verheyen, Walter

1996-01-01

1. Rainfall data were collated for years preceding historical outbreaks of Mastomys rats in East Africa in order to test the hypothesis that such outbreaks occur after long dry periods. 2. Rodent outbreaks were generally not preceded by long dry periods. 3. Population dynamics of Mastomys...... natalensis rats in Tanzania are significantly affected by the distribution of rainfall during the rainy season. 4. All previous rodent outbreaks in Tanzania were preceded by abundant rainfall early in the rainy season, i.e, towards the end of the year. 5. A flow chart is constructed to assess the likelihood...

Old World hantaviruses in rodents in New Orleans, Louisiana.

Science.gov (United States)

Cross, Robert W; Waffa, Bradley; Freeman, Ashley; Riegel, Claudia; Moses, Lina M; Bennett, Andrew; Safronetz, David; Fischer, Elizabeth R; Feldmann, Heinz; Voss, Thomas G; Bausch, Daniel G

2014-05-01

Seoul virus, an Old World hantavirus, is maintained in brown rats and causes a mild form of hemorrhagic fever with renal syndrome (HFRS) in humans. We captured rodents in New Orleans, Louisiana and tested them for the presence of Old World hantaviruses by reverse transcription polymerase chain reaction (RT-PCR) with sequencing, cell culture, and electron microscopy; 6 (3.4%) of 178 rodents captured--all brown rats--were positive for a Seoul virus variant previously coined Tchoupitoulas virus, which was noted in rodents in New Orleans in the 1980s. The finding of Tchoupitoulas virus in New Orleans over 25 years since its first discovery suggests stable endemicity in the city. Although the degree to which this virus causes human infection and disease remains unknown, repeated demonstration of Seoul virus in rodent populations, recent cases of laboratory-confirmed HFRS in some US cities, and a possible link with hypertensive renal disease warrant additional investigation in both rodents and humans.

Attenuation of ethanol abstinence-induced anxiety- and depressive-like behavior by the phosphodiesterase-4 inhibitor rolipram in rodents.

Science.gov (United States)

Gong, Mei-Fang; Wen, Rui-Ting; Xu, Ying; Pan, Jian-Chun; Fei, Ning; Zhou, Yan-Meng; Xu, Jiang-Ping; Liang, Jian-Hui; Zhang, Han-Ting

2017-10-01

Withdrawal symptoms stand as a core feature of alcohol dependence. Our previous results have shown that inhibition of phosphodiesterase-4 (PDE4) decreased ethanol seeking and drinking in alcohol-preferring rodents. However, little is known about whether PDE4 is involved in ethanol abstinence-related behavior. The objective of this study was to characterize the role of PDE4 in the development of anxiety- and depressive-like behavior induced by abstinence from ethanol exposure in different animal models. Using three rodent models of ethanol abstinence, we examined the effects of rolipram, a prototypical, selective PDE4 inhibitor, on (1) anxiety-like behavior induced by repeated ethanol abstinence in the elevated plus maze test in fawn-hooded (FH/Wjd) rats, (2) anxiety-like behavior in the open-field test and light-dark transition test following acute ethanol abstinence in C57BL/6J mice, and (3) anxiety- and depressive-like behavior induced by protracted ethanol abstinence in the elevated plus maze, forced-swim, and tail-suspension tests in C57BL/6J mice. Pretreatment with rolipram (0.1 or 0.2 mg/kg) significantly increased entries and time spent in the open arms of the elevated plus maze test in rats with repeated ethanol abstinence. Similarly, in mice with acute ethanol abstinence, administration of rolipram (0.25 or 0.5 mg/kg) dose-dependently increased the crossings in the central zone of the open-field test and duration and transitions on the light side of the light-dark transition test, suggesting anxiolytic-like effects of rolipram. Consistent with these, chronic treatment with rolipram (0.1, 0.3, or 1.0 mg/kg) increased entries in the open arms of the elevated plus maze test; it also reduced the increased duration of immobility in both the forced-swim and tail-suspension tests in mice after protracted ethanol abstinence, suggesting antidepressant-like effects of rolipram. These results provide the first demonstration for that PDE4 plays a role in modulating

Evaluating rodent motor functions: Which tests to choose?

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Schönfeld, Lisa-Maria; Dooley, Dearbhaile; Jahanshahi, Ali; Temel, Yasin; Hendrix, Sven

2017-12-01

Damage to the motor cortex induced by stroke or traumatic brain injury (TBI) can result in chronic motor deficits. For the development and improvement of therapies, animal models which possess symptoms comparable to the clinical population are used. However, the use of experimental animals raises valid ethical and methodological concerns. To decrease discomfort by experimental procedures and to increase the quality of results, non-invasive and sensitive rodent motor tests are needed. A broad variety of rodent motor tests are available to determine deficits after stroke or TBI. The current review describes and evaluates motor tests that fall into three categories: Tests to evaluate fine motor skills and grip strength, tests for gait and inter-limb coordination and neurological deficit scores. In this review, we share our thoughts on standardized data presentation to increase data comparability between studies. We also critically evaluate current methods and provide recommendations for choosing the best behavioral test for a new research line. Copyright © 2017 Elsevier Ltd. All rights reserved.

Specific and strain-independent effects of dexamethasone in the prevention and treatment of experimental autoimmune encephalomyelitis in rodents

DEFF Research Database (Denmark)

Donia, M; Mangano, K; Quattrocchi, C

2010-01-01

Experimental autoimmune encephalomyelitis in rodents (EAE) is a generally accepted in vivo model for immunopathogenic mechanisms underlying multiple sclerosis (MS). There are, however, different forms of rodent EAE, and therapeutic regimens may affect these forms differently. We have therefore te...... predictors of drug efficacy in at least some variants of human MS. Better understanding of the clinical and immunopharmacologic features of these models might prove useful when testing new drug candidates for MS treatment....

Effects of early life adverse experiences on brain activity: Implications from maternal separation models in rodents

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Mayumi eNishi

2014-06-01

Full Text Available During postnatal development, adverse early life experiences can affect the formation of neuronal circuits and exert long-lasting influences on neural function. Many studies have shown that daily repeated MS, an animal model of early life stress, can modulate the hypothalamic-pituitary-adrenal axis (HPA axis and can affect subsequent brain function and emotional behavior during adulthood. However, the molecular basis of the long-lasting effects of early life stress on brain function has not been completely elucidated. In this review, we introduce various cases of MS in rodents and illustrate the alterations in HPA axis activity by focusing on corticosterone (CORT, an end product of the HPA axis in rodents. We then present a characterization of the brain regions affected by various patterns of MS, including repeated MS and single time MS at various stages before weaning, by investigating c-Fos expression, a biological marker of neuronal activity. These CORT and c-Fos studies suggest that repeated early life stress may affect neuronal function in region- and temporal-specific manners, indicating a critical period for habituation to early life stress. Next, we discuss how early life stress can impact behavior, namely by inducing depression, anxiety or eating disorders. Furthermore, alterations in gene expression in adult mice exposed to MS, especially epigenetic changes of DNA methylation, are discussed.

Comparison of two rodent models of maternal separation on juvenile social behavior

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Betty eZimmerberg

2011-06-01

Full Text Available Early childhood deprivation is associated with an increased risk of attachment disorders and psychopathology. The neural consequences of exposure to stress early in life have used two major rodent models to provide important tools for translational research. Although both models have been termed Maternal Separation, the paradigms differ in ways that clearly shift the focus of stress between maternal and offspring units. The first model, here called Early Deprivation (ED, isolates pups individually while the dam is left not alone, but with a subset of littermates in the home nest (Stay-at-homes. The other model, here called Maternal Separation (MS, isolates the dam in a novel cage while the pups are separated together. In this study, these two early stress models were directly compared for their effects on social behaviors in male and female juvenile offspring. Although both models altered play behavior compared to controls, patterns of prosocial behaviors versus submissive behaviors differed by model and sex. Additionally, there were main effects of sex, with female ED subjects exhibited masculinizing effects of early stress during play sessions. Maternal behavior upon reunion with the isolated subjects was significantly increased in the MS condition compared to both ED and control conditions, which also differed but by a lesser magnitude. Stay-at-homes were tested since some laboratories use them for controls rather than undisturbed litters; they displayed significantly different sex-dependent play compared to undisturbed subjects. These results indicate that early stress effects vary by paradigm of separation. We suggest that MS produces greater stress on the dam and thus greater maternal mediation, while ED causes greater stress on the neonates, resulting in different behavioral sequela that warrant attention when using these models for translational research.

Establishing a cat model of acute optic nerve injury

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

BACKGROUND: In order to investigate the progress in optic nerve injury and the following regeneration and repair, many kinds of animal models of optic nerve injury have been established, such as models of acute and chronic ocular hypertension, compression, amputating wound, ischemia reperfusion or hypoxia,intravitreal injection of excitatory amino acids, etc. However, most of these models are established by squeezing intraorbital optic nerve, and suitable for ophthalmology, and there are fewer models suitable for the acute cranial contusion in neurosurgery.OBJECTIVE: To observe the changes of optic nerve after acute injury, and the characteristics of methods for establishing model of acute optic nerve injury in cats.DESIGN: A complete randomized grouping and controlled animal trial.SETTING: Department of Neurosurgery, General Hospital of Ji'nan Military Area Command of Chinese PLA.MATERIALS: Twenty-eight healthy adult cats, common degree, either sex, weighing 2.0 - 3.5 kg, were provided by the animal experimental center of Fudan University. The cats were randomly divided into control group (n =3) and model group (n =25), and 5 cats in the model group were observed at 6 hours and 1,3, 7 and 14 days after injury respectively. JX-2000 biological signal processing system (Department of Physiology, Second Military Medical University of Chinese PLA, Shanghai); Inverted phase contrast microscope (Olympus); Axioplan 2 imaging microgram analytical system (Labsystems).METHODS: The experiments were carried out in the Department of Neurosurgery, General Hospital of Jinan Military Area Command of Chinese PLA from June 2004 to June 2005. The cats in the model groups were made into models of acute optic nerve injury: The cats were anesthetized, then the limbs were fixed in a lateral recumbent position. Pterion approach in human was imitated, the operative incision was made along the line between lateral canthus and tragus, and it could be seen deep along the skull base that white

Bipolar electrocautery: A rodent model of Sunderland third-degree nerve injury.

Science.gov (United States)

Moradzadeh, Arash; Brenner, Michael J; Whitlock, Elizabeth L; Tong, Alice Y; Luciano, Janina P; Hunter, Daniel A; Myckatyn, Terence M; Mackinnon, Susan E

2010-01-01

To determine the Sunderland classification of a bipolar electrocautery injury. Twenty-two rats received crush (a reproducible Sunderland second-degree injury) or bipolar electrocautery injury and were evaluated for functional, histomorphometric, and immunohistochemical recovery at 21 or 42 days. Animal experiments were performed between July 3 and December 12, 2007. Axonal regeneration and end plate reinnervation were evaluated in double transgenic cyan fluorescent protein-conjugated Thy1 and green fluorescent protein-conjugated S100 mice. Compared with crush injury, bipolar electrocautery injury caused greater disruption of myelin and neurofilament architecture at the injury site and decreased nerve fiber counts and percentage of neural tissue distal to the injury (P =.007). Complete functional recovery was seen after crush but not bipolar electrocautery injury. Serial live imaging demonstrated axonal regeneration at week 1 after crush and at week 3 after bipolar electrocautery injury. Qualitative assessment of motor end plate reinnervation at 42 days demonstrated complete neuromuscular end plate reinnervation in the crush group and only limited reinnervation in the bipolar electrocautery group. Bipolar electrocautery injury in a rodent model resulted in a Sunderland third-degree injury, characterized by gradual, incomplete recovery without intervention.

Argininosuccinate synthetase as a plasma biomarker of liver injury after acetaminophen overdose in rodents and humans

Science.gov (United States)

McGill, Mitchell R.; Cao, Mengde; Svetlov, Archie; Sharpe, Matthew R.; Williams, C. David; Curry, Steven C.; Farhood, Anwar; Jaeschke, Hartmut; Svetlov, Stanislav I.

2014-01-01

Context New biomarkers are needed in acetaminophen (APAP) hepatotoxicity. Plasma argininosuccinate synthetase (ASS) is a promising candidate. Objective Characterize ASS in APAP hepatotoxicity. Methods ASS was measured in plasma from rodents and humans with APAP hepatotoxicity. Results In mice, ASS increased before injury, peaked before ALT, and decreased rapidly. Fischer rats had a greater increase in ASS relative to ALT. Patients with abnormal liver test results had very high ASS compared to controls. ASS appeared to increase early in some patients, and declined rapidly in all. Conclusions : ASS may be a useful biomarker of acute cell death in APAP hepatotoxicity. PMID:24597531

Multiple Co-infections of Rodents with Hantaviruses, Leptospira, and Babesia in Croatia

Science.gov (United States)

Turk, Nenad; Korva, Miša; Margaletić, Josip; Beck, Relja; Vucelja, Marko; Habuš, Josipa; Svoboda, Petra; Županc, Tatjana Avšič; Henttonen, Heikki; Markotić, Alemka

2012-01-01

Abstract Hantaviruses, Leptospira spp., and Babesia spp. are rodent-borne pathogens present worldwide. We studied multiple co-infections of small rodents in Croatia with all three pathogens. Twenty-eight Apodemus flavicollis and 16 Myodes glareolus were tested for the presence of hantavirus RNA by real-time RT-PCR, Leptospira strains by renoculture method and Babesia DNA by PCR. Anti-hantavirus antibodies and anti-Leptospira antibodies were detected by serological methods. Very high infection rates with each pathogen were found in A. flavicollis: 20 of 28 rodents (71%) were infected with Dobrava virus, 13 rodents (46%) were infected with Leptospira, and 5 rodents (18%) were infected with Babesia. Multiple co-infections with all three pathogens were found in 3 of 28 (11%) A. flavicollis animals, suggesting that the same rodent host can be infected with several pathogens at the same time. Dual infections with both hantaviruses and Leptospira were found in 7 of 44 rodents (16%), with hantaviruses and Babesia in 2 rodents (5%), and double infection with both Leptospira and Babesia were found in 1 rodent (2%). Since hantaviruses, Leptospira, and Babesia have similar geographical distributions, it is to be expected that in other parts of the world multiple co-infections, representing a serious threat to public health, can be found. PMID:22217170

Acute leukemia classification by ensemble particle swarm model selection.

Science.gov (United States)

Escalante, Hugo Jair; Montes-y-Gómez, Manuel; González, Jesús A; Gómez-Gil, Pilar; Altamirano, Leopoldo; Reyes, Carlos A; Reta, Carolina; Rosales, Alejandro

2012-07-01

Acute leukemia is a malignant disease that affects a large proportion of the world population. Different types and subtypes of acute leukemia require different treatments. In order to assign the correct treatment, a physician must identify the leukemia type or subtype. Advanced and precise methods are available for identifying leukemia types, but they are very expensive and not available in most hospitals in developing countries. Thus, alternative methods have been proposed. An option explored in this paper is based on the morphological properties of bone marrow images, where features are extracted from medical images and standard machine learning techniques are used to build leukemia type classifiers. This paper studies the use of ensemble particle swarm model selection (EPSMS), which is an automated tool for the selection of classification models, in the context of acute leukemia classification. EPSMS is the application of particle swarm optimization to the exploration of the search space of ensembles that can be formed by heterogeneous classification models in a machine learning toolbox. EPSMS does not require prior domain knowledge and it is able to select highly accurate classification models without user intervention. Furthermore, specific models can be used for different classification tasks. We report experimental results for acute leukemia classification with real data and show that EPSMS outperformed the best results obtained using manually designed classifiers with the same data. The highest performance using EPSMS was of 97.68% for two-type classification problems and of 94.21% for more than two types problems. To the best of our knowledge, these are the best results reported for this data set. Compared with previous studies, these improvements were consistent among different type/subtype classification tasks, different features extracted from images, and different feature extraction regions. The performance improvements were statistically significant

Transformation of the rodent malaria parasite Plasmodium chabaudi

OpenAIRE

Spence, Philip J; Cunningham, Deirdre; Jarra, William; Lawton, Jennifer; Langhorne, Jean; Thompson, Joanne

2011-01-01

The rodent malaria parasite Plasmodium chabaudi chabaudi shares many features with human malaria species, including P. falciparum, and is the in vivo model of choice for many aspects of malaria research in the mammalian host, from sequestration of parasitized erythrocytes, to antigenic variation and host immunity and immunopathology. this protocol describes an optimized method for the transformation of mature blood-stage P.c. chabaudi and a description of a vector that targets efficient, sing...

Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy

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Julia M. Post

2018-03-01

Full Text Available Research on the antiepileptic effects of (endo-cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]. Concomitant research has uncovered the contribution of neuroinflammatory processes and peripheral immunity to the onset and progression of epilepsy. Accordingly, modulation of inflammatory pathways such as cyclooxygenase-2 (COX-2 was pursued as alternative therapeutic strategy for epilepsy. Palmitoylethanolamide (PEA is an endogenous fatty acid amide related to the centrally and peripherally present eCB AEA, and is a naturally occurring nutrient that has long been recognized for its analgesic and anti-inflammatory properties. Neuroprotective and anti-hyperalgesic properties of PEA were evidenced in neurodegenerative diseases, and antiepileptic effects in pentylenetetrazol (PTZ, maximal electroshock (MES and amygdaloid kindling models of epileptic seizures. Moreover, numerous clinical trials in chronic pain revealed that PEA treatment is devoid of addiction potential, dose limiting side effects and psychoactive effects, rendering PEA an appealing candidate as antiepileptic compound or adjuvant. In the present study, we aimed at assessing antiepileptic properties of PEA in a mouse model of acute epileptic seizures induced by systemic administration of kainic acid (KA. KA-induced epilepsy in rodents is assumed to resemble to different extents human temporal lobe epilepsy (TLE depending on the route of KA administration; intracerebral (i

Leptospira and rodents in Cambodia : environmental determinants of infection

OpenAIRE

Ivanova, S.; Herbreteau, Vincent; Blasdell, K.; Chaval, Y.; Buchy, P.; Guillard, B.; Morand, S.

2012-01-01

We investigated infection of rodents and shrews by Leptospira spp. in two localities of Cambodia (Veal Renh, Kaev Seima) and in four types of habitat (forests, non-flooded lands, lowland rain-fed paddy fields, houses) during the wet and the dry seasons. Habitat preference was common, and rodent and shrew species were found only in houses or in rain-fed paddy fields or in forests. Among 649 small mammals trapped belonging to 12 rodent species and 1 shrew species, 71 of 642 animals tested were ...

Disruption of the Serotonergic System after Neonatal Hypoxia-Ischemia in a Rodent Model

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Kathryn M. Buller

2012-01-01

Full Text Available Identifying which specific neuronal phenotypes are vulnerable to neonatal hypoxia-ischemia, where in the brain they are damaged, and the mechanisms that produce neuronal losses are critical to determine the anatomical substrates responsible for neurological impairments in hypoxic-ischemic brain-injured neonates. Here we describe our current work investigating how the serotonergic network in the brain is disrupted in a rodent model of preterm hypoxia-ischemia. One week after postnatal day 3 hypoxia-ischemia, losses of serotonergic raphé neurons, reductions in serotonin levels in the brain, and reduced serotonin transporter expression are evident. These changes can be prevented using two anti-inflammatory interventions; the postinsult administration of minocycline or ibuprofen. However, each drug has its own limitations and benefits for use in neonates to stem damage to the serotonergic network after hypoxia-ischemia. By understanding the fundamental mechanisms underpinning hypoxia-ischemia-induced serotonergic damage we will hopefully move closer to developing a successful clinical intervention to treat neonatal brain injury.

Tularemia and plague survey in rodents in an earthquake zone in southeastern Iran

Science.gov (United States)

Gyuranecz, Miklós

2015-01-01

OBJECTIVES: Earthquakes are one the most common natural disasters that lead to increased mortality and morbidity from transmissible diseases, partially because the rodents displaced by an earthquake can lead to an increased rate of disease transmission. The aim of this study was to evaluate the prevalence of plague and tularemia in rodents in the earthquake zones in southeastern Iran. METHODS: In April 2013, a research team was dispatched to explore the possible presence of diseases in rodents displaced by a recent earthquake magnitude 7.7 around the cities of Khash and Saravan in Sistan and Baluchestan Province. Rodents were trapped near and in the earthquake zone, in a location where an outbreak of tularemia was reported in 2007. Rodent serums were tested for a serological survey using an enzyme-linked immunosorbent assay. RESULTS: In the 13 areas that were studied, nine rodents were caught over a total of 200 trap-days. Forty-eight fleas and 10 ticks were obtained from the rodents. The ticks were from the Hyalomma genus and the fleas were from the Xenopsylla genus. All the trapped rodents were Tatera indica. Serological results were negative for plague, but the serum agglutination test was positive for tularemia in one of the rodents. Tatera indica has never been previously documented to be involved in the transmission of tularemia. CONCLUSIONS: No evidence of the plague cycle was found in the rodents of the area, but evidence was found of tularemia infection in rodents, as demonstrated by a positive serological test for tularemia in one rodent. PMID:26602769

Assessment of cisplatin-induced kidney injury using an integrated rodent platform

Energy Technology Data Exchange (ETDEWEB)

Chen, Yafei [Global Safety Assessment, AstraZeneca R and D Waltham, MA 02451 (United States); Brott, David [Patient Safety, AstraZeneca R and D Wilmington, DE 19850 (United States); Luo, Wenli [Discovery Statistics, AstraZeneca R and D Waltham, MA 02451 (United States); Gangl, Eric [DMPK, AstraZeneca R and D Waltham, MA 02451 (United States); Kamendi, Harriet; Barthlow, Herbert; Lengel, David; Fikes, James; Kinter, Lewis [Global Safety Assessment, AstraZeneca R and D Waltham, MA 02451 (United States); Valentin, Jean-Pierre [Global Safety Assessment, AstraZeneca R and D Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Bialecki, Russell, E-mail: russell.bialecki@astrazeneca.com [Global Safety Assessment, AstraZeneca R and D Waltham, MA 02451 (United States)

2013-05-01

Current diagnosis of drug-induced kidney injury (DIKI) primarily relies on detection of elevated plasma creatinine (Cr) or blood urea nitrogen (BUN) levels; however, both are indices of overall kidney function and changes are delayed with respect to onset of nephron injury. Our aim was to investigate whether early changes in new urinary DIKI biomarkers predict plasma Cr, BUN, renal hemodynamic and kidney morphological changes associated with kidney injury following a single dose of cisplatin (CDDP) using an integrated platform in rodent. Conscious surgically prepared male Han Wistar rats were given a single intraperitoneal dose of CDDP (15 mg/kg). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urinalysis, DIKI biomarkers, CDDP pharmacokinetics, blood pressures, heart rate, body temperature and electroencephalogram (EEG) were measured in the same vehicle- or CDDP-treated animals over 72 h. Plasma chemistry (including Cr and BUN) and renal tissues were examined at study termination. Cisplatin caused progressive reductions of GFR, ERPF, heart rate and body temperature from day 1 (0–24 h). DIKI biomarkers including alpha-glutathione S-transferase (α-GST) significantly increased as early as 6 h post-dose, which preceded significant declines of GFR and ERPF (24 h), increased plasma Cr and BUN (72 h), and associated with renal acute tubular necrosis at 72 h post-dose. The present study adds to the current understanding of CDDP action by demonstrating that early increases in urinary excretion of α-GST predict DIKI risk following acute exposure to CDDP in rats, before changes in traditional DIKI markers are evident. - Highlights: ► CDDP causes direct damage to kidneys without affecting EEG or CVS function. ► α-GST and albumin detect DIKI earlier when compared with traditional indices. ► Integrated “cardiovascular-EEG-renal” model to better understand DIKI mechanisms ► Promotes 3R's principles in drug discovery and development.

Assessment of cisplatin-induced kidney injury using an integrated rodent platform

International Nuclear Information System (INIS)

Chen, Yafei; Brott, David; Luo, Wenli; Gangl, Eric; Kamendi, Harriet; Barthlow, Herbert; Lengel, David; Fikes, James; Kinter, Lewis; Valentin, Jean-Pierre; Bialecki, Russell

2013-01-01

Current diagnosis of drug-induced kidney injury (DIKI) primarily relies on detection of elevated plasma creatinine (Cr) or blood urea nitrogen (BUN) levels; however, both are indices of overall kidney function and changes are delayed with respect to onset of nephron injury. Our aim was to investigate whether early changes in new urinary DIKI biomarkers predict plasma Cr, BUN, renal hemodynamic and kidney morphological changes associated with kidney injury following a single dose of cisplatin (CDDP) using an integrated platform in rodent. Conscious surgically prepared male Han Wistar rats were given a single intraperitoneal dose of CDDP (15 mg/kg). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urinalysis, DIKI biomarkers, CDDP pharmacokinetics, blood pressures, heart rate, body temperature and electroencephalogram (EEG) were measured in the same vehicle- or CDDP-treated animals over 72 h. Plasma chemistry (including Cr and BUN) and renal tissues were examined at study termination. Cisplatin caused progressive reductions of GFR, ERPF, heart rate and body temperature from day 1 (0–24 h). DIKI biomarkers including alpha-glutathione S-transferase (α-GST) significantly increased as early as 6 h post-dose, which preceded significant declines of GFR and ERPF (24 h), increased plasma Cr and BUN (72 h), and associated with renal acute tubular necrosis at 72 h post-dose. The present study adds to the current understanding of CDDP action by demonstrating that early increases in urinary excretion of α-GST predict DIKI risk following acute exposure to CDDP in rats, before changes in traditional DIKI markers are evident. - Highlights: ► CDDP causes direct damage to kidneys without affecting EEG or CVS function. ► α-GST and albumin detect DIKI earlier when compared with traditional indices. ► Integrated “cardiovascular-EEG-renal” model to better understand DIKI mechanisms ► Promotes 3R's principles in drug discovery and development

Semi-Autonomous Rodent Habitat for Deep Space Exploration

Science.gov (United States)

Alwood, J. S.; Shirazi-Fard, Y.; Pletcher, D.; Globus, R.

2018-01-01

NASA has flown animals to space as part of trailblazing missions and to understand the biological responses to spaceflight. Mice traveled in the Lunar Module with the Apollo 17 astronauts and now mice are frequent research subjects in LEO on the ISS. The ISS rodent missions have focused on unravelling biological mechanisms, better understanding risks to astronaut health, and testing candidate countermeasures. A critical barrier for longer-duration animal missions is the need for humans-in-the-loop to perform animal husbandry and perform routine tasks during a mission. Using autonomous or telerobotic systems to alleviate some of these tasks would enable longer-duration missions to be performed at the Deep Space Gateway. Rodent missions performed using the Gateway as a platform could address a number of critical risks identified by the Human Research Program (HRP), as well as Space Biology Program questions identified by NRC Decadal Survey on Biological and Physical Sciences in Space, (2011). HRP risk areas of potentially greatest relevance that the Gateway rodent missions can address include those related to visual impairment (VIIP) and radiation risks to central nervous system, cardiovascular disease, as well as countermeasure testing. Space Biology focus areas addressed by the Gateway rodent missions include mechanisms and combinatorial effects of microgravity and radiation. The objectives of the work proposed here are to 1) develop capability for semi-autonomous rodent research in cis-lunar orbit, 2) conduct key experiments for testing countermeasures against low gravity and space radiation. The hardware and operations system developed will enable experiments at least one month in duration, which potentially could be extended to one year in duration. To gain novel insights into the health risks to crew of deep space travel (i.e., exposure to space radiation), results obtained from Gateway flight rodents can be compared to ground control groups and separate groups

Altered Tracer Distribution and Clearance in the Extracellular Space of the Substantia Nigra in a Rodent Model of Parkinson's Disease

Directory of Open Access Journals (Sweden)

Yuan Fang

2017-07-01

Full Text Available The relationship between extracellular space (ECS diffusion parameters and brain drug clearance is not well-studied, especially in the context of Parkinson's disease (PD. Therefore, we used a rodent model of PD to explore the distribution and clearance of a magnetic resonance tracer. Forty male Sprague Dawley rats were randomized into four different groups: a PD group, a Madopar group (PD + Madopar treatment, a sham group, and a control group. All rats received an injection of the extracellular tracer gadolinium-diethylene triaminepentacetic acid (Gd-DTPA directly into the substantia nigra (SN. ECS diffusion parameters including the effective diffusion coefficient (D*, clearance coefficient (k', ratio of the maximum distribution volume of the tracer (Vd-max%, and half-life (t1/2 were measured. We found that all parameters were significantly increased in the PD group compared to the other three groups (D*: F = 5.774, p = 0.0025; k': F = 20.00, P < 0.0001; Vd-max%: F = 12.81, P < 0.0001; and t1/2: F = 23.35, P < 0.0001. In conclusion, the PD group exhibited a wider distribution and lower clearance of the tracer compared to the other groups. Moreover, k' was more sensitive than D* for monitoring morphological and functional changes in the ECS in a rodent model of PD.

Study of hantavirus infection in captive breed colonies of wild rodents

Directory of Open Access Journals (Sweden)

RC Oliveira

2004-10-01

Full Text Available Wild sigmondontine rodents are known to be the reservoir of several serotypes of New World hantaviruses. The mechanism of viral transmission is by aerosol inhalation of the excreta from infected rodents. Considering that the captive breed colonies of various wild mammals may present a potencial risk for hantaviral transmission, we examined 85 speciemens of Thrichomys spp. (Echimyidae and 17 speciemens of Nectomys squamipes (Sigmodontinae from our colony for the presence of hantavirus infections. Blood samples were assayed for the presence of antibodies to Andes nucleocapsid antigen using enzyme-linked immunosorbent assay (ELISA. Additionally, serum samples from workers previously exposed to wild rodents, in the laboratories where the study was conducted, were also tested by ELISA to investigate prevalence of anti-hantavirus IgG antibodies. All blood samples were negative for hantavirus antibodies. Although these results suggest that those rodent's colonies are hantavirus free, the work emphasizes the need for hantavirus serological monitoring in wild colonized rodents and secure handling potentially infected rodents as important biosafety measures.

Thieving rodents as substitute dispersers of megafaunal seeds

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Jansen, Patrick A.; Hirsch, Ben T.; Emsens, Willem-Jan; Zamora-Gutierrez, Veronica; Wikelski, Martin; Kays, Roland

2012-01-01

The Neotropics have many plant species that seem to be adapted for seed dispersal by megafauna that went extinct in the late Pleistocene. Given the crucial importance of seed dispersal for plant persistence, it remains a mystery how these plants have survived more than 10,000 y without their mutualist dispersers. Here we present support for the hypothesis that secondary seed dispersal by scatter-hoarding rodents has facilitated the persistence of these large-seeded species. We used miniature radio transmitters to track the dispersal of reputedly megafaunal seeds by Central American agoutis, which scatter-hoard seeds in shallow caches in the soil throughout the forest. We found that seeds were initially cached at mostly short distances and then quickly dug up again. However, rather than eating the recovered seeds, agoutis continued to move and recache the seeds, up to 36 times. Agoutis dispersed an estimated 35% of seeds for >100 m. An estimated 14% of the cached seeds survived to the next year, when a new fruit crop became available to the rodents. Serial video-monitoring of cached seeds revealed that the stepwise dispersal was caused by agoutis repeatedly stealing and recaching each other’s buried seeds. Although previous studies suggest that rodents are poor dispersers, we demonstrate that communities of rodents can in fact provide highly effective long-distance seed dispersal. Our findings suggest that thieving scatter-hoarding rodents could substitute for extinct megafaunal seed dispersers of tropical large-seeded trees. PMID:22802644

A vapourized Δ(9)-tetrahydrocannabinol (Δ(9)-THC) delivery system part II: comparison of behavioural effects of pulmonary versus parenteral cannabinoid exposure in rodents.

Science.gov (United States)

Manwell, Laurie A; Ford, Brittany; Matthews, Brittany A; Heipel, Heather; Mallet, Paul E

2014-01-01

Studies of the rewarding and addictive properties of cannabinoids using rodents as animal models of human behaviour often fail to replicate findings from human studies. Animal studies typically employ parenteral routes of administration, whereas humans typically smoke cannabis, thus discrepancies may be related to different pharmacokinetics of parenteral and pulmonary routes of administration. Accordingly, a novel delivery system of vapourized Δ(9)-tetrahydrocannabinol (Δ(9)-THC) was developed and assessed for its pharmacokinetic, pharmacodynamic, and behavioural effects in rodents. A commercially available vapourizer was used to assess the effects of pulmonary (vapourized) administration of Δ(9)-THC and directly compared to parenteral (intraperitoneal, IP) administration of Δ(9)-THC. Sprague-Dawley rats were exposed to pure Δ(9)-THC vapour (1, 2, 5, 10, and 20mg/pad), using a Volcano® vapourizing device (Storz and Bickel, Germany) or IP-administered Δ(9)-THC (0.1, 0.3, 0.5, 1.0mg/kg), and drug effects on locomotor activity, food and water consumption, and cross-sensitization to morphine (5mg/kg) were measured. Vapourized Δ(9)-THC significantly increased feeding during the first hour following exposure, whereas IP-administered Δ(9)-THC failed to produce a reliable increase in feeding at all doses tested. Acute administration of 10mg of vapourized Δ(9)-THC induced a short-lasting stimulation in locomotor activity compared to control in the first of four hours of testing over 7days of repeated exposure; this chronic exposure to 10mg of vapourized Δ(9)-THC did not induce behavioural sensitization to morphine. These results suggest vapourized Δ(9)-THC administration produces behavioural effects qualitatively different from those induced by IP administration in rodents. Furthermore, vapourized Δ(9)-THC delivery in rodents may produce behavioural effects more comparable to those observed in humans. We conclude that some of the conflicting findings in animal

Measuring Motivation and Reward-Related Decision Making in the Rodent Operant Touchscreen System.

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Heath, Christopher J; Phillips, Benjamin U; Bussey, Timothy J; Saksida, Lisa M

2016-01-04

This unit is designed to facilitate implementation of the fixed and progressive ratio paradigms and the effort-related choice task in the rodent touchscreen apparatus to permit direct measurement of motivation and reward-related decision making in this equipment. These protocols have been optimized for use in the mouse and reliably yield stable performance levels that can be enhanced or suppressed by systemic pharmacological manipulation. Instructions are also provided for the adjustment of task parameters to permit use in mouse models of neurodegenerative disease. These tasks expand the utility of the rodent touchscreen apparatus beyond the currently available battery of cognitive assessment paradigms. Copyright © 2016 John Wiley & Sons, Inc.

Olfactory discrimination and memory deficits in the Flinders Sensitive Line rodent model of depression.

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Cook, A; Pfeiffer, L-M; Thiele, S; Coenen, V A; Döbrössy, M D

2017-10-01

Major Depressive Disorder (MDD) is a heterogeneous psychiatric disorder with broad symptomatic manifestations. The current study examined, for the first time, olfactory memory and discrimination in the Flinders Sensitive Line (FSL) rodent model of depression. Male FSL rats and controls were trained on an Olfactory Discrimination (OD) and a Social Interaction (SI) test. On the OD test, the FSL and controls performed similarly at the shortest inter-trial interval (5min), however, with extended delay of 30min, the FSLs had a recall and odour discrimination deficit. At the longest delay (60min) both groups performed poorly. The FSL rats i.) had a deficit in olfactory discrimination suggesting impairment in olfactory memory and recall; ii.) were less likely to socialize with unfamiliar rats. The data suggests that FSL animals have an impaired olfactory information processing capacity. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of rodents in avian influenza outbreaks in poultry farms: a review.

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Velkers, Francisca C; Blokhuis, Simon J; Veldhuis Kroeze, Edwin J B; Burt, Sara A

2017-12-01

Wild migratory birds are associated with global avian influenza virus (AIV) spread. Although direct contact with wild birds and contaminated fomites is unlikely in modern non-free range poultry farms applying biosecurity measures, AIV outbreaks still occur. This suggests involvement of other intermediate factors for virus transmission between wild birds and poultry. This review describes current evidence of the potential role of rodents in AIV transmission from wild birds to poultry and between poultry houses. Rodents can be abundant around poultry houses, share their habitat with waterfowl and can readily enter poultry houses. Survival of AIV from waterfowl in poultry house surroundings and on the coat of rodents suggests that rodents are likely to act as mechanical vector. AIVs can replicate in rodents without adaptation, resulting in high viral titres in lungs and nasal turbinates, virus presence in nasal washes and saliva, and transmission to naïve contact animals. Therefore, active AIV shedding by infected rodents may play a role in transmission to poultry. Further field and experimental studies are needed to provide evidence for a role of rodents in AIV epidemiology. Making poultry houses rodent-proof and the immediate surroundings unattractive for rodents are recommended as preventive measures against possible AIV introduction.

Insulin acutely upregulates protein expression of the fatty acid transporter CD36 in human skeletal muscle in vivo

NARCIS (Netherlands)

Corpeleijn, E.; Pelsers, M.M.A.L.; Soenen, S.; Mensink, M.; Bouwman, F.G.; Kooi, M.E.; Saris, W.H.M.; Glatz, J.F.C.; Blaak, E.E.

2008-01-01

Enhanced fatty acid uptake may lead to the accumulation of lipid intermediates. This is related to insulin resistance and type 2 diabetes mellitus. Rodent studies suggest that fatty acid transporters are acutely regulated by insulin. We investigated differences in fatty acid transporter content

Accelerated cognitive decline in a rodent model for temporal lobe epilepsy.

Science.gov (United States)

Schipper, Sandra; Aalbers, Marlien W; Rijkers, Kim; Lagiere, Melanie; Bogaarts, Jan G; Blokland, Arjan; Klinkenberg, Sylvia; Hoogland, Govert; Vles, Johan S H

2016-12-01

Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent model for temporal lobe epilepsy. Neurobehavioral assessment was performed before and after surgery, after the induction of self-sustaining limbic status epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent seizures. Furthermore, we assessed potential confounders of memory performance. Rats showed a deficit in spatial working memory after the induction of the SSLSE, which endured in the chronic phase. A progressive decline in recognition memory developed in SSLSE rats. Confounding factors were absent. Seizure frequency and also the severity of the status epilepticus were not correlated with the severity of cognitive deficits. The effect of the seizure frequency on cognitive comorbidity in epilepsy has long been debated, possibly because of confounders such as antiepileptic medication and the heterogeneity of epileptic etiologies. In an animal model of temporal lobe epilepsy, we showed that a decrease in spatial working memory does not relate to the seizure frequency. This suggests for other mechanisms are responsible for memory decline and potentially a common pathophysiology of cognitive deterioration and the occurrence and development of epileptic seizures. Identifying this common denominator will allow development of more targeted interventions treating cognitive decline in patients with epilepsy. The treatment of interictal symptoms will increase the quality of life of many patients with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Classification of Multiple Seizure-Like States in Three Different Rodent Models of Epileptogenesis.

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Guirgis, Mirna; Serletis, Demitre; Zhang, Jane; Florez, Carlos; Dian, Joshua A; Carlen, Peter L; Bardakjian, Berj L

2014-01-01

Epilepsy is a dynamical disease and its effects are evident in over fifty million people worldwide. This study focused on objective classification of the multiple states involved in the brain's epileptiform activity. Four datasets from three different rodent hippocampal preparations were explored, wherein seizure-like-events (SLE) were induced by the perfusion of a low - Mg(2+) /high-K(+) solution or 4-Aminopyridine. Local field potentials were recorded from CA3 pyramidal neurons and interneurons and modeled as Markov processes. Specifically, hidden Markov models (HMM) were used to determine the nature of the states present. Properties of the Hilbert transform were used to construct the feature spaces for HMM training. By sequentially applying the HMM training algorithm, multiple states were identified both in episodes of SLE and nonSLE activity. Specifically, preSLE and postSLE states were differentiated and multiple inner SLE states were identified. This was accomplished using features extracted from the lower frequencies (1-4 Hz, 4-8 Hz) alongside those of both the low- (40-100 Hz) and high-gamma (100-200 Hz) of the recorded electrical activity. The learning paradigm of this HMM-based system eliminates the inherent bias associated with other learning algorithms that depend on predetermined state segmentation and renders it an appropriate candidate for SLE classification.

Activity of nucleic acid polymers in rodent models of HBV infection.

Science.gov (United States)

Schöneweis, Katrin; Motter, Neil; Roppert, Pia L; Lu, Mengji; Wang, Baoju; Roehl, Ingo; Glebe, Dieter; Yang, Dongliang; Morrey, John D; Roggendorf, Michael; Vaillant, Andrew

2018-01-01

Nucleic acid polymers (NAPs) block the release of HBsAg from infected hepatocytes. These compounds have been previously shown to have the unique ability to eliminate serum surface antigen in DHBV-infected Pekin ducks and achieve multilog reduction of HBsAg or HBsAg loss in patients with chronic HBV infection and HBV/HDV coinfection. In ducks and humans, the blockage of HBsAg release by NAPs occurs by the selective targeting of the assembly and/or secretion of subviral particles (SVPs). The clinically active NAP species REP 2055 and REP 2139 were investigated in other relevant animal models of HBV infection including woodchucks chronically infected with WHV, HBV transgenic mice and HBV infected SCID-Hu mice. The liver accumulation of REP 2139 in woodchucks following subcutaneous administration was examined and was found to be similar to that observed in mice and ducks. However, in woodchucks, NAP treatment was associated with only mild (36-79% relative to baseline) reductions in WHsAg (4/10 animals) after 3-5 weeks of treatment without changes in serum WHV DNA. In HBV infected SCID-Hu mice, REP 2055 treatment was not associated with any reduction of HBsAg, HBeAg or HBV DNA in the serum after 28 days of treatment. In HBV transgenic mice, no reductions in serum HBsAg were observed with REP 2139 with up to 12 weeks of treatment. In conclusion, the antiviral effects of NAPs in DHBV infected ducks and patients with chronic HBV infection were weak or absent in woodchuck and mouse models despite similar liver accumulation of NAPs in all these species, suggesting that the mechanisms of SVP assembly and or secretion present in rodent models differs from that in DHBV and chronic HBV infections. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Identification of Alpha and Beta Coronavirus in Wildlife Species in France: Bats, Rodents, Rabbits, and Hedgehogs

Directory of Open Access Journals (Sweden)

Elodie Monchatre-Leroy

2017-11-01

Full Text Available Coronaviruses are closely monitored in the context of emerging diseases and, as illustrated with Severe Acute Respiratory Syndrome coronavirus (SARS-CoV and Middle East Respiratory Syndrome-coronavirus (MERS-CoV, are known to cross the species barrier and eventually to move from wildlife to humans. Knowledge of the diversity of coronaviruses in wildlife is therefore essential to better understand and prevent emergence events. This study explored the presence of coronaviruses in four wild mammal orders in France: Bats, rodents, lagomorphs, and hedgehogs. Betacoronavirus and Alphacoronavirus genera were identified. The results obtained suggest the circulation of potentially evolving virus strains, with the potential to cross the species barrier.

Landscape epidemiology in urban environments: The example of rodent-borne Trypanosoma in Niamey, Niger.

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Rossi, Jean-Pierre; Kadaouré, Ibrahima; Godefroid, Martin; Dobigny, Gauthier

2017-10-05

Trypanosomes are protozoan parasites found worldwide, infecting humans and animals. In the past decade, the number of reports on atypical human cases due to Trypanosoma lewisi or T. lewisi-like has increased urging to investigate the multiple factors driving the disease dynamics, particularly in cities where rodents and humans co-exist at high densities. In the present survey, we used a species distribution model, Maxent, to assess the spatial pattern of Trypanosoma-positive rodents in the city of Niamey. The explanatory variables were landscape metrics describing urban landscape composition and physiognomy computed from 8 land-cover classes. We computed the metrics around each data location using a set of circular buffers of increasing radii (20m, 40m, 60m, 80m and 100m). For each spatial resolution, we determined the optimal combination of feature class and regularization multipliers by fitting Maxent with the full dataset. Since our dataset was small (114 occurrences) we expected an important uncertainty associated to data partitioning into calibration and evaluation datasets. We thus performed 350 independent model runs with a training dataset representing a random subset of 80% of the occurrences and the optimal Maxent parameters. Each model yielded a map of habitat suitability over Niamey, which was transformed into a binary map implementing a threshold maximizing the sensitivity and the specificity. The resulting binary maps were combined to display the proportion of models that indicated a good environmental suitability for Trypanosoma-positive rodents. Maxent performed better with landscape metrics derived from buffers of 80m. Habitat suitability for Trypanosoma-positive rodents exhibited large patches linked to urban features such as patch richness and the proportion of landscape covered by concrete or tarred areas. Such inferences could be helpful in assessing areas at risk, setting of monitoring programs, public and medical staff awareness or even

Towards sustainable management of rodents in organic animal husbandry

NARCIS (Netherlands)

Meerburg, B.G.; Bonde, M.; Brom, F.W.A.; Endepols, S.; Jensen, A.N.; Leirs, H.; Lodal, J.; Singleton, G.R.; Pelz, H.J.; Rodenburg, T.B.; Kijlstra, A.

2004-01-01

From 26 to 28 May 2004 an international seminar was held in Wageningen, the Netherlands, about current knowledge and advice on rodent management on organic pig and poultry farms in Western Europe. This paper summarizes the discussions. Rodent management is necessary to protect the food production

Effect of combined doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea using rat (Sprague- Dawley) models of conditioned gaping.

Science.gov (United States)

Rock, Erin M; Limebeer, Cheryl L; Parker, Linda A

2015-12-01

Δ(9)-Tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) found in cannabis both reduce the distressing symptom of nausea, but their combined effects are not understood. The potential of combined doses of THC and CBDA to reduce acute nausea and anticipatory nausea in rodent models was assessed. For acute nausea, the potential of cannabinoid pretreatment(s) to reduce LiCl-induced nausea paired with saccharin was evaluated in a subsequent drug free taste reactivity test, followed by a taste avoidance test. For anticipatory nausea, the potential of the cannabinoid pretreatment(s) to reduce the expression of LiCl-induced contextually elicited conditioned gaping was evaluated. Combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) reduced acute nausea. Higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses also reduced acute nausea. THC (10 mg/kg) interfered with conditioned taste avoidance, an effect attenuated by CBDA (10 μg/kg). On the other hand, combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) did not suppress contextually elicited conditioned gaping in a test for anticipatory nausea. However, higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses, also reduced anticipatory nausea. Only at the highest dose (10 mg/kg) did THC impair locomotor activity, but CBDA did not at any dose. Combined subthreshold doses of THC:CBDA are particularly effective as a treatment for acute nausea. At higher doses, CBDA may attenuate THC-induced interference with learning.

Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions

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Tony Schountz

2014-03-01

Full Text Available Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships.

Central melanopsin projections in the diurnal rodent, Arvicanthis niloticus

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Jennifer Lou Langel

2015-07-01

Full Text Available The direct effects of photic stimuli on behavior are very different in diurnal and nocturnal species, as light stimulates an increase in activity in the former and a decrease in the latter. Studies of nocturnal mice have implicated a select population of retinal ganglion cells that are intrinsically photosensitive (ipRGCs in mediation of these acute responses to light. ipRGCs are photosensitive due to the expression of the photopigment melanopsin; these cells use glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP as neurotransmitters. PACAP is useful for the study of central ipRGC projections because, in the retina, it is found exclusively within melanopsin cells. Little is known about the central projections of ipRGCs in diurnal species. Here, we first characterized these cells in the retina of the diurnal Nile grass rat using immunohistochemistry (IHC. The same basic subtypes of melanopsin cells that have been described in other mammals were present, but nearly 25% of them were displaced, primarily in its superior region. PACAP was present in 87.7% of all melanopsin cells, while 97.4% of PACAP cells contained melanopsin. We then investigated central projections of ipRGCs by examining the distribution of immunoreactive PACAP fibers in intact and enucleated animals. This revealed evidence that these cells project to the suprachiasmatic nucleus, lateral geniculate nucleus (LGN, pretectum and superior colliculus. This distribution was confirmed with injections of cholera toxin subunit β coupled with Alexa Fluor 488 in one eye and Alexa Flour 594 in the other, combined with IHC staining of PACAP. These studies also revealed that the ventral and dorsal LGN and the caudal olivary pretectal nucleus receive less innervation from ipRGCs than that reported in nocturnal rodents. Overall, these data suggest that although ipRGCs and their projections are very similar in diurnal and nocturnal rodents, they may not be identical.

Effects of rodent community diversity and composition on prevalence of an endemic bacterial pathogen - Bartonella

Science.gov (United States)

Bai, Y.; Kosoy, M.Y.; Calisher, C.H.; Cully, J.F.; Collinge, S.K.

2009-01-01

By studying Bartonella prevalence in rodent communities from 23 geographic sites in the western United States and one site in northern Mexico, the present study focused on the effects of rodent community diversity (measured by richness and Shannon index) and composition on prevalence of Bartonella infections. The analysis showed negative correlations of Bartonella prevalence with rodent richness and Shannon index. Further, Bartonella prevalence varied among rodent genera/species. Three models were applied to explain the observations. (1) Within-species/genus transmission: Bartonella strains usually are host-specific and adding non-host species would decrease Bartonella prevalence in its principal host through reduction of host contact (encounter reduction); (2) Frequency-dependence: Adding hosts would decrease the proportion of all infected individuals in the community, resulting in a reduction in the number of contacts between susceptible and infected individuals that usually leads to transmission (transmission reduction); and (3) Dominant species effect: Dominant species, if not susceptible to Bartonellae, can constrain the abundance of susceptible hosts (susceptible host regulation). These mechanisms work in concert; and the level of Bartonella prevalence is an outcome of regulation of all of these mechanisms on the entire system.

An evidence-based approach to case management model selection for an acute care facility: is there really a preferred model?

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Terra, Sandra M

2007-01-01

This research seeks to determine whether there is adequate evidence-based justification for selection of one acute care case management model over another. Acute Inpatient Hospital. This article presents a systematic review of published case management literature, resulting in classification specific to terms of level of evidence. This review examines the best available evidence in an effort to select an acute care case management model. Although no single case management model can be identified as preferred, it is clear that adequate evidence-based literature exists to acknowledge key factors driving the acute care model and to form a foundation for the efficacy of hospital case management practice. Although no single case management model can be identified as preferred, this systematic review demonstrates that adequate evidence-based literature exists to acknowledge key factors driving the acute care model and forming a foundation for the efficacy of hospital case management practice. Distinctive aspects of case management frameworks can be used to guide the development of an acute care case management model. The study illustrates: * The effectiveness of case management when there is direct patient contact by the case manager regardless of disease condition: not only does the quality of care increase but also length of stay (LOS) decreases, care is defragmented, and both patient and physician satisfaction can increase. * The preferred case management models result in measurable outcomes that can directly relate to, and demonstrate alignment with, organizational strategy. * Acute care management programs reduce cost and LOS, and improve outcomes. * An integrated case management program that includes social workers, as well as nursing, is the most effective acute care management model. * The successful case management model will recognize physicians, as well as patients, as valued customers with whom partnership can positively affect financial outcomes in terms of

Population dynamics of Rodents and Insectivores in lowland tropical ...

African Journals Online (AJOL)

The community structure of rodents and insectivores in the lowland tropical rainforest of Okomu National Park, Edo State, Nigeria was assessed using a combination of live-trapping and sighting techniques during the dry and wet seasons. Seventeen species (14 species of rodent, 3 species of insectivores) were captured, ...

Multiple infections of rodents with zoonotic pathogens in Austria.

Science.gov (United States)

Schmidt, Sabrina; Essbauer, Sandra S; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald; Ulrich, Rainer G

2014-07-01

Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host-pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans.

Ossicular bone modeling in acute otitis media

DEFF Research Database (Denmark)

Salomonsen, Rasmus Lysholdt; Hermansson, Ann; Cayé-Thomasen, Per

2010-01-01

A number of middle ear diseases are associated with pathologic bone modeling, either formative or resorptive. As such, the pathogenesis of a sclerotic mastoid has been controversial for decades. Experimental studies on acute middle ear infection have shown progressive osteoneogenesis in the bone ...

Farmer survey in the hinterland of Kisangani (Democratic Republic of Congo) on rodent crop damage and rodent control techniques used

DEFF Research Database (Denmark)

Drazo, Nicaise Amundala; Kennis, Jan; Leirs, Herwig

2008-01-01

We conducted a survey on rodent crop damage among farmers in the hinterland of Kisangani (Democratic Republic of Congo). We studied the amount of crop damage, the rodent groups causing crop damage, the growth stages affected and the control techniques used. We conducted this survey in three...... municipalities using a standard questionnaire form translated into local languages, between November 2005 and June 2006 and during July 2007. We used the Quotas method and interviewed 70 households per municipality. Farmers indicated rodent groups implicated in crop damage on color photographs. Two types...... of survey techniques were used: individual and focus-group surveys. The sugar cane rat, Thryonomys sp. and Lemniscomys striatus caused most damage to crops, but inside granaries, Rattus rattus was the primary pest species eating stored food supplies and causing damage to stored goods. Cassava and maize were...

Effects of acute sleep deprivation on motor and reversal learning in mice.

Science.gov (United States)

Varga, Andrew W; Kang, Mihwa; Ramesh, Priyanka V; Klann, Eric

2014-10-01

Sleep supports the formation of a variety of declarative and non-declarative memories, and sleep deprivation often impairs these types of memories. In human subjects, natural sleep either during a nap or overnight leads to long-lasting improvements in visuomotor and fine motor tasks, but rodent models recapitulating these findings have been scarce. Here we present evidence that 5h of acute sleep deprivation impairs mouse skilled reach learning compared to a matched period of ad libitum sleep. In sleeping mice, the duration of total sleep time during the 5h of sleep opportunity or during the first bout of sleep did not correlate with ultimate gain in motor performance. In addition, we observed that reversal learning during the skilled reaching task was also affected by sleep deprivation. Consistent with this observation, 5h of sleep deprivation also impaired reversal learning in the water-based Y-maze. In conclusion, acute sleep deprivation negatively impacts subsequent motor and reversal learning and memory. Copyright © 2014 Elsevier Inc. All rights reserved.

Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology

NARCIS (Netherlands)

Liang, W.; Menke, A.L.; Driessen, A.; Koek, G.H.; Lindeman, J.H.; Stoop, R.; Havekes, L.M.; Kleemann., R.; Hoek, A.M. van den

2014-01-01

Results: The criteria macrovesicular steatosis, microvesicular steatosis, hepatocellular hypertrophy, inflammation and fibrosis were generally applicable to rodent NAFLD. The inter-observer reproducibility (evaluated using the Intraclass Correlation Coefficient) between the ten observers was high

Gut microbiome may contribute to insulin resistance and systemic inflammation in obese rodents: a meta-analysis.

Science.gov (United States)

Jiao, Na; Baker, Susan S; Nugent, Colleen A; Tsompana, Maria; Cai, Liting; Wang, Yong; Buck, Michael J; Genco, Robert J; Baker, Robert D; Zhu, Ruixin; Zhu, Lixin

2018-04-01

A number of studies have associated obesity with altered gut microbiota, although results are discordant regarding compositional changes in the gut microbiota of obese animals. Herein we used a meta-analysis to obtain an unbiased evaluation of structural and functional changes of the gut microbiota in diet-induced obese rodents. The raw sequencing data of nine studies generated from high-fat diet (HFD)-induced obese rodent models were processed with QIIME to obtain gut microbiota compositions. Biological functions were predicted and annotated with KEGG pathways with PICRUSt. No significant difference was observed for alpha diversity and Bacteroidetes-to-Firmicutes ratio between obese and lean rodents. Bacteroidia, Clostridia, Bacilli, and Erysipelotrichi were dominant classes, but gut microbiota compositions varied among studies. Meta-analysis of the nine microbiome data sets identified 15 differential taxa and 57 differential pathways between obese and lean rodents. In obese rodents, increased abundance was observed for Dorea, Oscillospira, and Ruminococcus, known for fermenting polysaccharide into short chain fatty acids (SCFAs). Decreased Turicibacter and increased Lactococcus are consistent with elevated inflammation in the obese status. Differential functional pathways of the gut microbiome in obese rodents included enriched pyruvate metabolism, butanoate metabolism, propanoate metabolism, pentose phosphate pathway, fatty acid biosynthesis, and glycerolipid metabolism pathways. These pathways converge in the function of carbohydrate metabolism, SCFA metabolism, and biosynthesis of lipid. HFD-induced obesity results in structural and functional dysbiosis of gut microbiota. The altered gut microbiome may contribute to obesity development by promoting insulin resistance and systemic inflammation.

Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.

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Inna Sukhotinsky

Full Text Available Epilepsy is a devastating disease, currently treated with medications, surgery or electrical stimulation. None of these approaches is totally effective and our ability to control seizures remains limited and complicated by frequent side effects. The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats. Hippocampal pyramidal neurons were transduced in vivo with a virus carrying an enhanced halorhodopsin (eNpHR, a yellow light activated chloride pump, and acute seizure progression was then monitored behaviorally and electrophysiologically in the presence and absence of illumination delivered via an optical fiber. Inhibition of those neurons with illumination prior to seizure onset significantly delayed electrographic and behavioral initiation of status epilepticus, and altered the dynamics of ictal activity development. These results reveal an essential role of hippocampal excitatory neurons in this model of ictogenesis and illustrate the power of optogenetic approaches for elucidation of seizure mechanisms. This early success in controlling seizures also suggests future therapeutic avenues.

Ecology of rodents at an old quarry in Zambia

African Journals Online (AJOL)

Ecology of rodents at an old quarry in Zambia. E.N. Chidumayo. Livingstone Museum, Zambia. An old quarry, 2,5 hain size near Livingstone in southern. Zambia was kill- and live-trapped between September 1974 and December 1976 to determine ecological relations among. rodent species inhabiting it. Seven species ...

Sleep in the Cape Mole Rat: A Short-Sleeping Subterranean Rodent.

Science.gov (United States)

Kruger, Jean-Leigh; Gravett, Nadine; Bhagwandin, Adhil; Bennett, Nigel C; Archer, Elizabeth K; Manger, Paul R

2016-01-01

The Cape mole rat Georychus capensis is a solitary subterranean rodent found in the western and southern Cape of South Africa. This approximately 200-gram bathyergid rodent shows a nocturnal circadian rhythm, but sleep in this species is yet to be investigated. Using telemetric recordings of the electroencephalogram (EEG) and electromyogram (EMG) in conjunction with video recordings, we were able to show that the Cape mole rat, like all other rodents, has sleep periods composed of both rapid eye movement (REM) and slow-wave (non-REM) sleep. These mole rats spent on average 15.4 h awake, 7.1 h in non-REM sleep and 1.5 h in REM sleep each day. Cape mole rats sleep substantially less than other similarly sized terrestrial rodents but have a similar percentage of total sleep time occupied by REM sleep. In addition, the duration of both non-REM and REM sleep episodes was markedly shorter in the Cape mole rat than has been observed in terrestrial rodents. Interestingly, these features (total sleep time and episode duration) are similar to those observed in another subterranean bathyergid mole rat, i.e. Fukomys mechowii. Thus, there appears to be a bathyergid type of sleep amongst the rodents that may be related to their environment and the effect of this on their circadian rhythm. Investigating further species of bathyergid mole rats may fully define the emerging picture of sleep in these subterranean African rodents. © 2016 S. Karger AG, Basel.

Natural Intestinal Protozoa in Rodents (Rodentia: Gerbillinae, Murinae, Cricetinae in Northwestern Iran

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Mehdi MOHEBALI

2017-09-01

Full Text Available Background: Majority of parasitic infections in rodents have zoonotic importance. This study aimed to determine the frequency and intensity of intestinal protozoa infections of rodents including Meriones persicus, Mus musculus and, Cricetulus migratorius.Methods: This survey was conducted in Meshkin Shahr district in northwestern Iran from Mar. to Dec. of 2014. Intestinal samples of 204 rodents including M. persicus (n=117, M. musculus (n=63 and C. migratorius (n=24 were parasitologically examined. Formalin-ether concentration method was done for all of rodents stool samples and observed with light microscope. All of suspected cases were stained with trichorome staining Method. Cultivation in dichromate potassium 2.5% was carried out for all of coccidian positive samples. Acid fast and aniline blue staining methods were used for detecting of coccidian oocysts and intestinal microsporidial spores, respectively.Results: About 121(59.3% of the caught rodents were generally infected with intestinal protozoa. Entamoeba muris 14(6.9%, Trichomonas muris 55(27.0%, Chilomastix betencourtti 17 (8.3%, Giardia muris 19(9.3%, Eimeria spp. 46(22.5%, Isospora spp. 4(2% and Cryptosporidium spp. 1(0.5% were found from the collected rodents. Microsporidian spores were identified in 63 (31% out of the 204 collected rodents using aniline blue staining method.Conclusion: Since some of the infections are zoonotic importance thus, control of rodents can be decreased new cases of the parasitic zoonoses in humans.

Natural Intestinal Protozoa in Rodents (Rodentia: Gerbillinae, Murinae, Cricetinae) in Northwestern Iran

Science.gov (United States)

MOHEBALI, Mehdi; ZAREI, Zabiholah; Khanaliha, Khadijeh; KIA, Eshrat Beigom; MOTAVALLI-HAGHI, Afsaneh; DAVOODI, Jaber; REZAEIAN, Tahereh; TARIGHI, Fathemeh; REZAEIAN, Mostafa

2017-01-01

Background: Majority of parasitic infections in rodents have zoonotic importance. This study aimed to determine the frequency and intensity of intestinal protozoa infections of rodents including Meriones persicus, Mus musculus and, Cricetulus migratorius. Methods: This survey was conducted in Meshkin Shahr district in northwestern Iran from Mar. to Dec. of 2014. Intestinal samples of 204 rodents including M. persicus (n=117), M. musculus (n=63) and C. migratorius (n=24) were parasitologically examined. Formalin-ether concentration method was done for all of rodents stool samples and observed with light microscope. All of suspected cases were stained with trichorome staining Method. Cultivation in dichromate potassium 2.5% was carried out for all of coccidian positive samples. Acid fast and aniline blue staining methods were used for detecting of coccidian oocysts and intestinal microsporidial spores, respectively. Results: About 121(59.3%) of the caught rodents were generally infected with intestinal protozoa. Entamoeba muris 14(6.9%), Trichomonas muris 55(27.0%), Chilomastix betencourtti 17 (8.3%), Giardia muris 19(9.3%), Eimeria spp. 46(22.5%), Isospora spp. 4(2%) and Cryptosporidium spp. 1(0.5%) were found from the collected rodents. Microsporidian spores were identified in 63 (31%) out of the 204 collected rodents using aniline blue staining method. Conclusion: Since some of the infections are zoonotic importance thus, control of rodents can be decreased new cases of the parasitic zoonoses in humans. PMID:28979348

Early Eocene rodents (Mammalia) from the Subathu Formation of ...

Indian Academy of Sciences (India)

1997a, b). Most of the rodents from this stratigraphic level have been referred to a rather diverse family Cha- pattimyidae ... Herein we describe a new early Eocene rodent assemblage .... thick zone of brownish red shales that occur as a ..... 1997b;. Plate 3, figure 31). ...... northwestern Pakistan and remarks on the collision.

Manipulation of nitric oxide in an animal model of acute liver injury ...

African Journals Online (AJOL)

We evaluated the impact of altering nitric oxide release on acute liver injury, the associated gut injury and bacterial translocation, at different time intervals. Methods: An acute rat liver injury model induced by D-galactosamine was used. Sprague Dawley rats were divided into four main groups: normal control, acute liver ...

Research Note. Occurrence of gastrointestinal helminths in commensal rodents from Tabasco, Mexico

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Cigarroa-Toledo N.

2017-06-01

Full Text Available The aim of this study was to determine the prevalence and species composition of helminths in commensal rodents captured inside private residences in the city of Villahermosa in Tabasco, Mexico. Trapping was performed at each house for three consecutive nights from October to December 2015. Fifty commensal rodents were captured: 23 Rattus norvegicus, 16 Mus musculus and 11 Rattus rattus. Rodents were transported alive to the laboratory and held in cages until they defecated. Feces were analyzed for helminth eggs using the Sheather’s flotation technique. The overall prevalence of helminths in rodents was 60 %: R. norvegicus was more likely to be parasitized (87.0 % than R. rattus (63.6 % and M. musculus (18.8 %. Eggs from at least 13 species of helminths were identified: Hymenolepis diminuta, Rodentolepis nana, Moniliformis moniliformis, Heligmosomoides polygyrus, Heterakis spumosa, Mastophorus muris, Nippostrongylus brasiliensis, Strongyloides ratti, Syphacia obvelata, Syphacia muris, Toxocara sp., Trichosomoides crassicauda, and Trichuris muris. This is the first study to report the presence of H. polygyrus, S. ratti and T. crassicauda in commensal rodents in Mexico. In conclusion, our results suggest that helminths commonly infect commensal rodents in Villahermosa and therefore rodents present a health risk to inhabitants in this region.

A Functional Analysis of Circadian Pacemakers in Nocturnal Rodents. IV. Entrainment : Pacemaker as Clock

NARCIS (Netherlands)

Pittendrigh, Colin S.; Daan, Serge

1976-01-01

1. In the first part of the paper, the model of non-parametric entrainment of circadian pacemakers is tested for the case of nocturnal rodents. The model makes use of the available data on freerunning period (τ) in constant darkness and on phase response curves (PRC) for short light pulses. It is

Wild rodents as a model to discover genes and pathways underlying natural variation in infectious disease susceptibility.

Science.gov (United States)

Turner, A K; Paterson, S

2013-11-01

Individuals vary in their susceptibility to infectious disease, and it is now well established that host genetic factors form a major component of this variation. The discovery of genes underlying susceptibility has the potential to lead to improved disease control, through the identification and management of vulnerable individuals and the discovery of novel therapeutic targets. Laboratory rodents have proved invaluable for ascertaining the function of genes involved in immunity to infection. However, these captive animals experience conditions very different to the natural environment, lacking the genetic diversity and environmental pressures characteristic of natural populations, including those of humans. It has therefore often proved difficult to translate basic laboratory research to the real world. In order to further our understanding of the genetic basis of infectious disease resistance, and the evolutionary forces that drive variation in susceptibility, we propose that genetic research traditionally conducted on laboratory animals is expanded to the more ecologically valid arena of natural populations. In this article, we highlight the potential of using wild rodents as a new resource for biomedical research, to link the functional genetic knowledge gained from laboratory rodents with the variation in infectious disease susceptibility observed in humans and other natural populations. © 2013 John Wiley & Sons Ltd.

Vitamin D depletion does not affect key aspects of the preeclamptic phenotype in a transgenic rodent model for preeclampsia

DEFF Research Database (Denmark)

Andersen, Louise Bjørkholt; Golic, Michaela; Przybyl, Lukasz

2016-01-01

Maternal vitamin D deficiency is proposed as a risk factor for preeclampsia in humans. We tested the hypothesis that vitamin D depletion aggravates and high supplementation ameliorates the preeclampsia phenotype in an established transgenic rat model of human renin-angiotensin system......-mediated preeclampsia. Adult rat dams, transgenic for human angiotensinogen (hAGT) and mated with male rats transgenic for human renin (hREN), were fed either vitamin D-depleted chow (VDd) or enriched chow (VDh) 2 weeks before mating and during pregnancy. Mean blood pressure was recorded by tail-cuff, and 24-hour urine...... of the preeclampsia phenotype using the transgenic rodent model of human renin-angiotensin system-mediated pre-eclampsia, plausibly due to altered vitamin D metabolism or excretion in the transgenic rats....

Bile salt-stimulated lipase plays an unexpected role in arthritis development in rodents.

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Susanne Lindquist

Full Text Available OBJECTIVE: The present study aimed to explore the hypothesis that bile salt-stimulated lipase (BSSL, in addition to being a key enzyme in dietary fat digestion during early infancy, plays an important role in inflammation, notably arthritis. METHODS: Collagen-induced arthritis (CIA and pristane-induced arthritis (PIA in rodents are commonly used experimental models that reproduce many of the pathogenic mechanisms of human rheumatoid arthritis, i.e. increased cellular infiltration, synovial hyperplasia, pannus formation, and erosion of cartilage and bone in the distal joints. We used the CIA model to compare the response in BSSL wild type (BSSL-WT mice with BSSL-deficient 'knock-out' (BSSL-KO and BSSL-heterozygous (BSSL-HET littermates. We also investigated if intraperitoneal injection of BSSL-neutralizing antibodies affected the development or severity of CIA and PIA in mice and rats, respectively. RESULTS: In two consecutive studies, we found that BSSL-KO male mice, in contrast to BSSL-WT littermates, were significantly protected from developing arthritis. We also found that BSSL-HET mice were less prone to develop disease compared to BSSL-WT mice, but not as resistant as BSSL-KO mice, suggesting a gene-dose effect. Moreover, we found that BSSL-neutralizing antibody injection reduced both the incidence and severity of CIA and PIA in rodents. CONCLUSION: Our data strongly support BSSL as a key player in the inflammatory process, at least in rodents. It also suggests the possibility that BSSL-neutralizing agents could serve as a therapeutic model to reduce the inflammatory response in humans.

Hypericum perforatum as a cognitive enhancer in rodents: A meta-analysis

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Ben-Eliezer, Daniel; Yechiam, Eldad

2016-01-01

Considered an antidepressant and anti-anxiety agent, Hypericum perforatum affects multiple neurotransmitters in a non-competitive synergistic manner, and may have nootropic potential. We quantitatively reviewed the pre-clinical literature to examine if there is a cognitive-enhancing effect of H. perforatum in healthy rodents. Additionally, within these studies, we compared the effects observed in intact rodents versus those whose performance has been impaired, mostly through stress manipulations. The meta-analysis incorporated studies that examined the effect of H. perforatum versus placebo on memory indices of task performance. All analyses were based on weighting different studies according to their inverse variance. Thirteen independent studies (published 2000–2014) involving 20 experimental comparisons met our inclusion criteria. The results showed a large positive effect of H. perforatum on cognitive performance for intact, healthy rodents (d = 1.11), though a larger effect emerged for stress-impaired rodents (d = 3.10 for restraint stress). The positive effect on intact rodents was observed in tasks assessing reference memory as well as working memory, and was not moderated by the type of memory or motivation (appetitive versus aversive). Thus, while primarily considered as a medication for depression, H. perforatum shows considerable nootropic potential in rodents. PMID:27762349

Neurogenic inflammation in human and rodent skin

DEFF Research Database (Denmark)

Schmelz, M; Petersen, Lars Jelstrup

2001-01-01

The combination of vasodilation and protein extravasation following activation of nociceptors has been termed "neurogenic inflammation." In contrast to rodents, no neurogenic protein extravasation can be elicited in healthy human skin. Dermal microdialysis has considerably increased our knowledge...... about neurogenic inflammation in human skin, including the involvement of mast cells.......The combination of vasodilation and protein extravasation following activation of nociceptors has been termed "neurogenic inflammation." In contrast to rodents, no neurogenic protein extravasation can be elicited in healthy human skin. Dermal microdialysis has considerably increased our knowledge...

Public Health Implications of Changing Rodent Importation Patterns - United States, 1999-2013.

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Lankau, E W; Sinclair, J R; Schroeder, B A; Galland, G G; Marano, N

2017-04-01

The United States imports a large volume of live wild and domestic animal species; these animals pose a demonstrated risk for introduction of zoonotic diseases. Rodents are imported for multiple purposes, including scientific research, zoo exhibits and the pet trade. Current U.S. public health regulatory restrictions specific to rodent importation pertain only to those of African origin. To understand the impacts of these regulations and the potential public health risks of international rodent trade to the United States, we evaluated live rodent import records during 1999-2013 by shipment volume and geographic origin, source (e.g. wild-caught versus captive- or commercially bred), intended purpose and rodent taxonomy. Live rodent imports increased from 2737 animals during 1999 to 173 761 animals during 2013. Increases in both the number and size of shipments contributed to this trend. The proportion of wild-captured imports declined from 75% during 1999 to guinea pigs and hamsters arriving from other countries in North America were predominant taxa underlying this trend. After 2003, African-origin imports became sporadic events under the federal permit process. These patterns suggest development of large-scale captive rodent breeding markets abroad for commercial sale in the United States. While the shift from wild-captured imports alleviates many conservation concerns and risks for novel disease emergence, such consolidated sourcing might elevate exposure risks for zoonotic diseases associated with high-density rodent breeding (e.g. lymphocytic choriomeningitis or salmonellosis). A responsive border health system must periodically re-evaluate importation regulations in conjunction with key stakeholders to ensure a balance between the economic benefits of rodent trade against the potential public health risks. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Effects of Climate and Rodent Factors on Hemorrhagic Fever with Renal Syndrome in Chongqing, China, 1997-2008.

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Yuntao Bai

Full Text Available China has the highest global incidence of hemorrhagic fever with renal syndrome (HFRS, constituting 90% of the cases in the world. Chongqing, located in the Three Gorges Reservoir Region, has been experiencing differences in the occurrence of HFRS from 1997 to 2008. The current study was designed to explore the effects of climate and rodent factors on the transmission of HFRS in Chongqing. Data on monthly HFRS cases, rodent strains, and climatic factors were collected from 1997 to 2008. Spatio-temporal analysis indicated that most HFRS cases were clustered in central Chongqing and that the incidence of HFRS decreased from 1997 to 2008. Poisson regression models showed that temperature (with lagged months of 0 and 5 and rainfall (with 2 lagged months were key climatic factors contributing to the transmission of HFRS. A zero-inflated negative binomial model revealed that rodent density was also significantly associated with the occurrence of HFRS in the Changshou district. The monthly trend in HFRS incidence was positively associated with rodent density and rainfall and negatively associated with temperature. Possible mechanisms are proposed through which construction of the dam influenced the incidence of HFRS in Chongqing. The findings of this study may contribute to the development of early warning systems for the control and prevention of HFRS in the Three Gorges Reservoir Region.

Multiparameter rodent chronic model for complex evaluation of alcoholism-mediated metabolic violations.

Science.gov (United States)

Shayakhmetova, Ganna M; Bondarenko, Larysa B; Kovalenko, Valentina M; Kharchenko, Olga I; Bohun, Larisa I; Omelchenko, Yuliya O

2015-01-01

Despite of the wide spectrum of alcoholism experimental models, the majority of them are very specialized on the short list of investigated parameters and could not provide reproduction of complex metabolic changes in the rats. The aim of the present study was to estimate whether rats selected by high alcohol preference, allowed free access to 15% alcohol for 150 days, develop simultaneous multilevel disturbances of cell macromolecules structure, metabolism and oxidative/nitrosative stress. Wistar albino male rats were divided into groups: I - rats selected by preferences to alcohol were used for chronic alcoholism modeling by replacing water with 15% ethanol (150 days), II - control. Contents of amino acids in serum, liver mRNA CYP2E1 and CYP3A2 expression, DNA fragmentation and lipid peroxidation levels, the reduced glutathione content, superoxide dismutase, catalase, iNOS and cNOS activities were evaluated. In serum of ethanol-treated rats contents of aspartic acid, serine, glycine, alanine and valine were decreased whereas contents of histidine, methionine and phenylalanine were increased. Liver CYP2E1, CYP3A2 mRNA expression, DNA fragmentation levels significantly elevated. Level of cNOS in ethanol-treated rat's hepatocytes was within the normal limits, whereas iNOS activity was raised 1.6 times. Liver pro- and anti-oxidant system alterations were shown. Rats' chronic 15% alcohol consumption (150 days) led solely to complex metabolomic changes at different levels, which simultaneously characterized cell macromolecules structure, metabolism, and oxidative/nitrosative stress. Rodent model of chronic alcoholism in the proposed modification could be an adequate and reasonably priced tool for further preclinical development and testing of pharmacotherapeutic agents.

Acute central neuropeptide Y administration increases food intake but does not affect hepatic very low-density lipoprotein (VLDL) production in mice

NARCIS (Netherlands)

Geerling, Janine J.; Wang, Yanan; Havekes, Louis M.; Romijn, Johannes A.; Rensen, Patrick C. N.

2013-01-01

Central neuropeptide Y (NPY) administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL)-triglyceride (TG) in rats. As hypertriglyceridemia is an important risk factor for

Effects of Erdosteine on Experimental Acute Pancreatitis Model.

Science.gov (United States)

Karapolat, Banu; Karapolat, Sami; Gurleyik, Emin; Yasar, Mehmet

2017-10-01

To create acute pancreatitis condition experimentally in rats using cerulein, and to reveal histopathological effects in pancreatic tissue with erdosteine. An experimental study. Department of General Surgery, Duzce University, Turkey, from June to October 2014. Thirty male Wistar albino rats were divided into three groups. No procedures were applied to Group 1. The rats in Group 2 and Group 3 were injected cerulein, to establish an experimental pancreatitis model and the blood amylase and lipase values were examined. The rats in Group 3 were given 10 mg/kg erdosteine. This treatment was continued for another 2 days and the rats were sacrificed. The pancreatic tissues were examined histopathologically for edema, inflammation, acinar necrosis, fat necrosis, and vacuolization. The lipase and amylase values and the histopathological examination of pancreatic tissues evidenced that the experimental acute pancreatitis model was established and edema, inflammation, acinar necrosis, fat necrosis, and vacuolization were observed in the pancreatic tissues. The statistical results suggest that erdosteine can decrease the edema, inflammation, acinar necrosis, fat necrosis and vacuolization scores in the tissues. The severity of acute pancreatitis, induced by cerulein in rats, is reduced with the use of erdosteine.

Large scale serial two-photon microscopy to investigate local vascular changes in whole rodent brain models of Alzheimer's disease

Science.gov (United States)

Delafontaine-Martel, P.; Lefebvre, J.; Damseh, R.; Castonguay, A.; Tardif, P.; Lesage, F.

2018-02-01

In this study, an automated serial two-photon microscope was used to image a fluorescent gelatin filled rodent's brain in 3D. A method to compute vascular density using automatic segmentation was combined with coregistration techniques to build group-level vasculature metrics. By studying the medial prefrontal cortex and the hippocampal formation of 3 age groups (2, 4.5 and 8 months old), we compared vascular density for both WT and an Alzheimer model transgenic brain (APP/PS1). We observe a loss of vascular density caused by the ageing process and we propose further analysis to confirm our results.

Public Health and Rodents: A Game of Cat and Mouse

NARCIS (Netherlands)

Meerburg, B.G.

2015-01-01

Rodents are the most abundant order of living mammals, distributed on every continent except Antarctic and represent 43 % of all mammalian species. Beside causing food losses and infrastructural damage, rodents can harbour pathogens that may cause serious problems to human and animal health.

A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD.

Science.gov (United States)

Davidsen, Peter K; Herbert, John M; Antczak, Philipp; Clarke, Kim; Ferrer, Elisabet; Peinado, Victor I; Gonzalez, Constancio; Roca, Josep; Egginton, Stuart; Barberá, Joan A; Falciani, Francesco

2014-01-01

A relatively large percentage of patients with chronic obstructive pulmonary disease (COPD) develop systemic co-morbidities that affect prognosis, among which muscle wasting is particularly debilitating. Despite significant research effort, the pathophysiology of this important extrapulmonary manifestation is still unclear. A key question that remains unanswered is to what extent systemic inflammatory mediators might play a role in this pathology. Cigarette smoke (CS) is the main risk factor for developing COPD and therefore animal models chronically exposed to CS have been proposed for mechanistic studies and biomarker discovery. Although mice have been successfully used as a pre-clinical in vivo model to study the pulmonary effects of acute and chronic CS exposure, data suggest that they may be inadequate models for studying the effects of CS on peripheral muscle function. In contrast, recent findings indicate that the guinea pig model (Cavia porcellus) may better mimic muscle wasting. We have used a systems biology approach to compare the transcriptional profile of hindlimb skeletal muscles from a Guinea pig rodent model exposed to CS and/or chronic hypoxia to COPD patients with muscle wasting. We show that guinea pigs exposed to long-term CS accurately reflect most of the transcriptional changes observed in dysfunctional limb muscle of severe COPD patients when compared to matched controls. Using network inference, we could then show that the expression profile in whole lung of genes encoding for soluble inflammatory mediators is informative of the molecular state of skeletal muscles in the guinea pig smoking model. Finally, we show that CXCL10 and CXCL9, two of the candidate systemic cytokines identified using this pre-clinical model, are indeed detected at significantly higher levels in serum of COPD patients, and that their serum protein level is inversely correlated with the expression of aerobic energy metabolism genes in skeletal muscle. We conclude that

Noninvasive Biomonitoring Approaches to Determine Dosimetry and Risk Following Acute Chemical Exposure: Analysis of Lead or Organophosphate Insecticide in Saliva

International Nuclear Information System (INIS)

Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.; Campbell, James A.; Lin, Yuehe

2004-01-01

There is a need to develop approaches for assessing risk associated with acute exposures to a broad-range of chemical agents and to rapidly determine the potential implications to human health. Non-invasive biomonitoring approaches are being developed using reliable portable analytical systems to quantitate dosimetry utilizing readily obtainable body fluids, such as saliva. Saliva has been used to evaluate a broad range of biomarkers, drugs, and environmental contaminants including heavy metals and pesticides. To advance the application of non-invasive biomonitoring a microfluidic/ electrochemical device has also been developed for the analysis of lead (Pb), using square wave anodic stripping voltammetry. The system demonstrates a linear response over a broad concentration range (1 2000 ppb) and is capable of quantitating saliva Pb in rats orally administered acute doses of Pb-acetate. Appropriate pharmacokinetic analyses have been used to quantitate systemic dosimetry based on determination of saliva Pb concentrations. In addition, saliva has recently been used to quantitate dosimetry following exposure to the organophosphate insecticide chlorpyrifos in a rodent model system by measuring the major metabolite, trichloropyridinol, and saliva cholinesterase inhibition following acute exposures. These results suggest that technology developed for non-invasive biomonitoring can provide a sensitive, and portable analytical tool capable of assessing exposure and risk in real-time. By coupling these non-invasive technologies with pharmacokinetic modeling it is feasible to rapidly quantitate acute exposure to a broad range of chemical agents. In summary, it is envisioned that once fully developed, these monitoring and modeling approaches will be useful for accessing acute exposure and health risk

First Isolates of Leptospira spp., from Rodents Captured in Angola

Science.gov (United States)

Fortes-Gabriel, Elsa; Carreira, Teresa; Vieira, Maria Luísa

2016-01-01

Rodents play an important role in the transmission of pathogenic Leptospira spp. However, in Angola, neither the natural reservoirs of these spirochetes nor leptospirosis diagnosis has been considered. Regarding this gap, we captured rodents in Luanda and Huambo provinces to identify circulating Leptospira spp. Rodent kidney tissue was cultured and DNA amplified and sequenced. Culture isolates were evaluated for pathogenic status and typing with rabbit antisera; polymerase chain reaction (PCR) and sequencing were also performed. A total of 37 rodents were captured: Rattus rattus (15, 40.5%), Rattus norvegicus (9, 24.3%), and Mus musculus (13, 35.2%). Leptospiral DNA was amplified in eight (21.6%) kidney samples. From the cultures, we obtained four (10.8%) Leptospira isolates belonging to the Icterohaemorrhagiae and Ballum serogroups of Leptospira interrogans and Leptospira borgpetersenii genospecies, respectively. This study provides information about circulating leptospires spread by rats and mice in Angola. PMID:26928840

Acute Central Neuropeptide Y Administration Increases Food Intake but Does Not Affect Hepatic Very Low-Density Lipoprotein (Vldl) Production in Mice

NARCIS (Netherlands)

Geerling, J.J.; Wang, Y.; Havekes, L.M.; Romijn, J.A.; Rensen, P.C.N.

2013-01-01

Objective: Central neuropeptide Y (NPY) administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL)-triglyceride (TG) in rats. As hypertriglyceridemia is an important risk factor for

Rhythmic 24 h variation of core body temperature and locomotor activity in a subterranean rodent (Ctenomys aff. knighti, the tuco-tuco.

Directory of Open Access Journals (Sweden)

Patricia Tachinardi

Full Text Available The tuco-tuco Ctenomys aff. knighti is a subterranean rodent which inhabits a semi-arid area in Northwestern Argentina. Although they live in underground burrows where environmental cycles are attenuated, they display robust, 24 h locomotor activity rhythms that are synchronized by light/dark cycles, both in laboratory and field conditions. The underground environment also poses energetic challenges (e.g. high-energy demands of digging, hypoxia, high humidity, low food availability that have motivated thermoregulation studies in several subterranean rodent species. By using chronobiological protocols, the present work aims to contribute towards these studies by exploring day-night variations of thermoregulatory functions in tuco-tucos, starting with body temperature and its temporal relationship to locomotor activity. Animals showed daily, 24 h body temperature rhythms that persisted even in constant darkness and temperature, synchronizing to a daily light/dark cycle, with highest values occurring during darkness hours. The range of oscillation of body temperature was slightly lower than those reported for similar-sized and dark-active rodents. Most rhythmic parameters, such as period and phase, did not change upon removal of the running wheel. Body temperature and locomotor activity rhythms were robustly associated in time. The former persisted even after removal of the acute effects of intense activity on body temperature by a statistical method. Finally, regression gradients between body temperature and activity were higher in the beginning of the night, suggesting day-night variation in thermal conductance and heat production. Consideration of these day-night variations in thermoregulatory processes is beneficial for further studies on thermoregulation and energetics of subterranean rodents.

Molecular Survey of Zoonotic Agents in Rodents and Other Small Mammals in Croatia.

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Tadin, Ante; Tokarz, Rafal; Markotić, Alemka; Margaletić, Josip; Turk, Nenad; Habuš, Josipa; Svoboda, Petra; Vucelja, Marko; Desai, Aaloki; Jain, Komal; Lipkin, W Ian

2016-02-01

Croatia is a focus for many rodent-borne zoonosis. Here, we report a survey of 242 rodents and small mammals, including 43 Myodes glareolus, 131 Apodemus flavicollis, 53 Apodemus agrarius, three Apodemus sylvaticus, six Sorex araneus, four Microtus arvalis, one Microtus agrestis, and one Muscardinus avellanarius, collected at eight sites in Croatia over an 8-year period. Multiplex MassTag polymerase chain reaction (PCR) was used for detection of Borrelia, Rickettsia, Bartonella, Babesia, Ehrlichia, Anaplasma, Francisella tularensis, and Coxiella burnetii. Individual PCR assays were used for detection of Leptospira, lymphocytic choriomeningitis virus, orthopoxviruses, flaviviruses, hantaviruses, and Toxoplasma gondii. Of the rodents, 52 (21.5%) were infected with Leptospira, 9 (3.7%) with Borrelia miyamotoi, 5 (2%) with Borrelia afzelii, 29 (12.0%) with Bartonella, 8 (3.3%) with Babesia microti, 2 (0.8%) with Ehrlichia, 4 (1.7%) with Anaplasma, 2 (0.8%) with F. tularensis, 43 (17.8%) with hantaviruses, and 1 (0.4%) with an orthopoxvirus. Other agents were not detected. Multiple infections were found in 32 rodents (13.2%): dual infections in 26 rodents (10.7%), triple infections in four rodents (2.9%), and quadruple infections in two rodents (0.8%). Our findings indicate that rodents in Croatia harbor a wide range of bacteria and viruses that are pathogenic to humans. © The American Society of Tropical Medicine and Hygiene.

Intraoperative laser speckle contrast imaging improves the stability of rodent middle cerebral artery occlusion model

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Yuan, Lu; Li, Yao; Li, Hangdao; Lu, Hongyang; Tong, Shanbao

2015-09-01

Rodent middle cerebral artery occlusion (MCAO) model is commonly used in stroke research. Creating a stable infarct volume has always been challenging for technicians due to the variances of animal anatomy and surgical operations. The depth of filament suture advancement strongly influences the infarct volume as well. We investigated the cerebral blood flow (CBF) changes in the affected cortex using laser speckle contrast imaging when advancing suture during MCAO surgery. The relative CBF drop area (CBF50, i.e., the percentage area with CBF less than 50% of the baseline) showed an increase from 20.9% to 69.1% when the insertion depth increased from 1.6 to 1.8 cm. Using the real-time CBF50 marker to guide suture insertion during the surgery, our animal experiments showed that intraoperative CBF-guided surgery could significantly improve the stability of MCAO with a more consistent infarct volume and less mortality.

Translational rodent models of Korsakoff syndrome reveal the critical neuroanatomical substrates of memory dysfunction and recovery.

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Savage, Lisa M; Hall, Joseph M; Resende, Leticia S

2012-06-01

Investigation of the amnesic disorder Korsakoff Syndrome (KS) has been vital in elucidating the critical brain regions involved in learning and memory. Although the thalamus and mammillary bodies are the primary sites of neuropathology in KS, functional deactivation of the hippocampus and certain cortical regions also contributes to the chronic cognitive dysfunction reported in KS. The rodent pyrithiamine-induced thiamine deficiency (PTD) model has been used to study the extent of hippocampal and cortical neuroadaptations in KS. In the PTD model, the hippocampus, frontal and retrosplenial cortical regions display loss of cholinergic innervation, decreases in behaviorally stimulated acetylcholine release and reductions in neurotrophins. While PTD treatment results in significant impairment in measures of spatial learning and memory, other cognitive processes are left intact and may be recruited to improve cognitive outcome. In addition, behavioral recovery can be stimulated in the PTD model by increasing acetylcholine levels in the medial septum, hippocampus and frontal cortex, but not in the retrosplenial cortex. These data indicate that although the hippocampus and frontal cortex are involved in the pathogenesis of KS, these regions retain neuroplasticity and may be critical targets for improving cognitive outcome in KS.

Wild Rodents as Experimental Intermediate Hosts of Lagochilascaris minor Leiper, 1909

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Julieta Machado Paçô

1999-07-01

Full Text Available A total of 25 specimens of Cavia porcellus (guinea pig, 5 Dasyprocta agouti (agouti, and 22 Calomys callosus (vesper mice were inoculated with infective eggs of Lagochilascaris minor. The inoculum was prepared with embryonated eggs and orally administered to each individual animal through an esophagus probe. In parallel, 100 specimens of Felis catus domesticus were individually fed with 55-70 nodules containing 3rd-stage larvae encysted in tissues of infected rodents. Animals were examined and necropsied at different time intervals. The migration and encystment of L3 larva was observed in viscera, skeletal muscle, adipose and subcutaneous tissues from all rodents. Adult worms localized at abscesses in the cervical region, rhino, and oropharynx were recovered from domestic cats inoculated with infected rodent tissues. Through this study we can conclude that: (1 wild rodents act as intermediate hosts, characterizing this ascarid heteroxenic cycle; (2 in natural conditions rodents could possibly act as either intermediate hosts or paratenic hosts of Lagochilascaris minor; (3 despite the occurrence of an auto-infecting cycle, in prime-infection of felines (definite hosts the cycle is only completed when intermediate hosts are provided; and (4 in the wild, rodents could serve as a source of infection for humans as they are frequently used as food in regions with the highest incidence of human lagochilascariasis.

Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors

DEFF Research Database (Denmark)

Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J

2017-01-01

to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect......Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads...... in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e...

Responses of nocturnal rodents to shrub encroachment in Banni grasslands, Gujarat, India

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Jayadevan, A.

2016-12-01

Shrub encroachment is one of the greatest threats to grasslands globally. These woodlands can strongly influence the behaviour of small mammals adapted to more open habitats, which rely on high visibility for early detection of predators. In semi-arid grasslands, rodents are considered keystone species. Although shrub encroachment is known to negatively affect rodent assemblages, its impact on the foraging behaviour of rodents, which is known to vary in response to risky situations, is unknown. Understanding whether shrub encroachment alters such antipredator behaviour is important as antipredator behaviour can alter the distribution, abundance and ultimately, survival of prey species. In this study, I explored the effects of shrub encroachment on the foraging behaviour of nocturnal rodent communities in the Banni grasslands, India. I examined foraging behaviour, quantified using the giving-up density (GUD) framework and the number of rodent crossings around food patches, in two habitats that differed in the extent of shrub encroachment. Under the GUD framework, the amount of food left behind by a forager in a food patch reflects the costs of feeding at the patch. Higher GUDs imply higher foraging costs. I also investigated how removal of an invasive woody plant, Prosopis juliflora would affect foraging behaviour of nocturnal rodents. High shrub encroachment was associated with higher foraging costs (higher GUDs) and lower activity than the sparsely wooded habitat, likely due to low visibility in the densely wooded habitat. The dense habitat also supported a higher richness and relative abundance of generalist rodents than the sparse habitat, likely due to the increased heterogeneity of the habitat. The tree removal experiment revealed that rodents had lower GUDs (i.e., low foraging costs) after the event of tree cutting. This may be due to the reduction of cover in the habitat, leading to higher visibility and lower predation risk. My results suggest that shrub

Effect of woodland patch size on rodent seed predation in a fragmented landscape

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J. Loman

2007-05-01

Full Text Available Predation on large woody plant seeds; chestnuts, acorns and sloe kernels, was studied in deciduous forests of two size classes: small woodlots (<1 ha and large woods (at least 25 ha in southern Sweden. Seeds used for the study were artificially distributed on the forest ground and seed predation measured as seed removal. Predation rate was similar in both types of woods. However, rodent density was higher in small woodlots and a correction for differences in rodent density showed that predation rate per individual rodent was higher in the large woods. This suggests that the small woodlots (including the border zone and their adjacent fields have more rodent food per area unit. A small woodlot cannot be considered a representative sample of a large continuous forest, even if the habitats appear similar. There was a strong effect of rodent density on seed predation rate. This suggests that rodents are major seed predators in this habitat.

Rodent Species Distribution and Hantavirus Seroprevalence in Residential and Forested areas of Sarawak, Malaysia.

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Hamdan, Nur Elfieyra Syazana; Ng, Yee Ling; Lee, Wei Bin; Tan, Cheng Siang; Khan, Faisal Ali Anwarali; Chong, Yee Ling

2017-01-01

Rodents belong to the order Rodentia, which consists of three families in Borneo (i.e., Muridae, Sciuridae and Hystricidae). These include rats, mice, squirrels, and porcupines. They are widespread throughout the world and considered pests that harm humans and livestock. Some rodent species are natural reservoirs of hantaviruses (Family: Bunyaviridae) that can cause zoonotic diseases in humans. Although hantavirus seropositive human sera were reported in Peninsular Malaysia in the early 1980s, information on their infection in rodent species in Malaysia is still lacking. The rodent populations in residential and forested areas in Sarawak were sampled. A total of 108 individuals from 15 species of rodents were collected in residential ( n = 44) and forested ( n = 64) areas. The species diversity of rodents in forested areas was significantly higher (H = 2.2342) compared to rodents in residential areas (H = 0.64715) ( p Sarawak, East Malaysia. The results suggested that hantavirus was not circulating in the studied rodent populations in Sarawak, or it was otherwise at a low prevalence that is below the detection threshold. It is important to remain vigilant because of the zoonotic potential of this virus and its severe disease outcome. Further studies, such as molecular detection of viral genetic materials, are needed to fully assess the risk of hantavirus infection in rodents and humans in this region of Malaysia.

Nutritional Evaluation of NASA's Rodent Food Bar Diet

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Barrett, Joyce E.; Yu, Diane S.; Dalton, Bonnie P.

2000-01-01

Tests are being conducted on NASA's rodent Food Bar in preparation for long-term use as the rat and mouse diet aboard the International Space Station. Nutritional analyses are performed after the bars are manufactured and then repeated periodically to determine nutritional stability. The primary factors analyzed are protein, ash, fat, fiber, moisture, amino acids, fatty acids, and minerals. Nutrient levels are compared to values published in the National Research Council's dietary requirements for rodents, and also to those contained in several commonly used commercial rodent lab diets. The Food Bar is manufactured from a powdered diet to which moisture is added as it is processed through an extruder. The bars are dipped into potassium sorbate, vacuum-sealed, and irradiated. In order to determine nutrient changes during extrusion and irradiation, the powdered diet, the non-irradiated bars, and the irradiated bars are all analyzed. We have observed lower values for some nutrients (iodine, vitamin K, and iron) in the Food Bars compared with NRC requirements. Many nutrients in the Food Bars are contained at a higher level than levels in the NRC requirements. An additional factor we are investigating is the 26% moisture level in the Food Bars, which drops to about 15% within a week, compared to a stable 10% moisture in many standard lab chow diets. In addition to the nutritional analyses, the food bar is being fed to several strains of rats and mice, and feeding study and necropsy results are being observed (Barrett et al, unpublished data). Information from the nutritional analyses and from the rodent studies will enable us to recommend the formulation that will most adequately meet the rodent Food Bar requirements for long-term use aboard the Space Station.

Considerations for the optimization of induced white matter injury preclinical models

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Abdullah Shafique Ahmad

2015-08-01

Full Text Available The white matter injury in relation to acute neurologic conditions, especially stroke, has remained obscure until recently. Current advances in the imaging technologies in the field of stroke have confirmed that white matter injury plays an important role in the prognosis of stroke and suggest that white matter protection is essential for functional recovery and post-stroke rehabilitation. However, due to the lack of a reproducible animal model of white matter injury, the pathophysiology and mechanisms of this injury are not well studied. Moreover, producing selective white matter injury in animals, especially in rodents, has proven to be challenging. Problems associated with inducing selective white matter ischemic injury in the rodent derive from differences in the architecture of the brain, most particularly the ratio of white matter to gray matter in rodents compared to humans, the agents used to induce the injury, and the location of the injury. Aging, gender differences, and comorbidities further add to this complexity. This review provides a brief account of the techniques commonly used to induce general white matter injury in animal models (stroke and non-stroke related and highlights relevance, optimization issues, and translational potentials associated with this particular form of injury.

The hip adductor muscle group in caviomorph rodents: anatomy and homology.

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García-Esponda, César M; Candela, Adriana M

2015-06-01

Anatomical comparative studies including myological data of caviomorph rodents are relatively scarce, leading to a lack of use of muscular features in cladistic and morphofunctional analyses. In rodents, the hip adductor muscles constitute an important group of the hindlimb musculature, having an important function during the beginning of the stance phase. These muscles are subdivided in several distinct ways in the different clades of rodents, making the identification of their homologies hard to establish. In this contribution we provide a detailed description of the anatomical variation of the hip adductor muscle group of different genera of caviomorph rodents and identify the homologies of these muscles in the context of Rodentia. On this basis, we identify the characteristic pattern of the hip adductor muscles in Caviomorpha. Our results indicate that caviomorphs present a singular pattern of the hip adductor musculature that distinguishes them from other groups of rodents. They are characterized by having a single m. adductor brevis that includes solely its genicular part. This muscle, together with the m. gracilis, composes a muscular sheet that is medial to all other muscles of the hip adductor group. Both muscles probably have a synergistic action during locomotion, where the m. adductor brevis reinforces the multiple functions of the m. gracilis in caviomorphs. Mapping of analyzed myological characters in the context of Rodentia indicates that several features are recovered as potential synapomorphies of caviomorphs. Thus, analysis of the myological data described here adds to the current knowledge of caviomorph rodents from anatomical and functional points of view, indicating that this group has features that clearly differentiate them from other rodents. Copyright © 2015 Elsevier GmbH. All rights reserved.

Helminth Infections of Rodents and Their Zoonotic Importance in Boyer-Ahmad District, Southwestern Iran.

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Ranjbar, Mohammad Javad; Sarkari, Bahador; Mowlavi, Gholam Reza; Seifollahi, Zeinab; Moshfe, Abdolali; Abdolahi Khabisi, Samaneh; Mobedi, Iraj

2017-01-01

Rodents are considered as reservoirs of various zoonotic diseases including helminthic infections. The current study aimed to evaluate the prevalence of helminth infections in rodents, in Boyer-Ahmad district, Southwestern Iran. Overall, 52 rodents were captured from various areas of the district by Sherman live traps. The animals were then euthanized and dissected. During necropsy, each organ was examined macroscopically for presence of any cyst or visible parasite. The gastrointestinal tract was removed and their contents were evaluated for larva or adult worms. Trichinella larvae in the rodents' muscles were investigated by both digestion and pathological methods. Twenty-eight (53.8%) of the trapped rodents were male. The rodents were including 25 (48.1%) Meriones persicus , 1(1.9%) Calomyscus bailwardi , 1 (1.9%) Arvicola terresterris , 7 (13.5%) Rattus rattus , 8 (15.4%) R. norvegicus , and 10 (19.2%) Apodemus sylvaticus . Of them, 38 (73.0%) were infected with at least one helminth. Collected rodents were infected with Hymenolepis diminuta (50%), Hymenolepis nana fraterna (28.8%), Skrjabinotaenia sp. (15.4%), Anoplocephalidae sp. (15.4%), Cysticercus fasciolaris (5.8%), Trichuris muris (36.5%), Aspiculuris tetraptera (15.4%), Syphacia sp. (5.7%), Rictularia sp. (15.4%), Trichostrongylus sp. (3.8%), and Gongylonema sp. (3.8%). M. persicus was the most (84%) infected rodent, yet the differences between rodent genus and helminth infectivity were not statistically significant ( P >0.05). The rodents in Boyer-Ahmad district are infected with different helminths infections that some of them are recognized as threat to human health.

First Isolates of Leptospira spp., from Rodents Captured in Angola.

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Fortes-Gabriel, Elsa; Carreira, Teresa; Vieira, Maria Luísa

2016-05-04

Rodents play an important role in the transmission of pathogenic Leptospira spp. However, in Angola, neither the natural reservoirs of these spirochetes nor leptospirosis diagnosis has been considered. Regarding this gap, we captured rodents in Luanda and Huambo provinces to identify circulating Leptospira spp. Rodent kidney tissue was cultured and DNA amplified and sequenced. Culture isolates were evaluated for pathogenic status and typing with rabbit antisera; polymerase chain reaction (PCR) and sequencing were also performed. A total of 37 rodents were captured: Rattus rattus (15, 40.5%), Rattus norvegicus (9, 24.3%), and Mus musculus (13, 35.2%). Leptospiral DNA was amplified in eight (21.6%) kidney samples. From the cultures, we obtained four (10.8%) Leptospira isolates belonging to the Icterohaemorrhagiae and Ballum serogroups of Leptospira interrogans and Leptospira borgpetersenii genospecies, respectively. This study provides information about circulating leptospires spread by rats and mice in Angola. © The American Society of Tropical Medicine and Hygiene.

Rodent Research on the International Space Station - A Look Forward

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Kapusta, A. B.; Smithwick, M.; Wigley, C. L.

2014-01-01

Rodent Research on the International Space Station (ISS) is one of the highest priority science activities being supported by NASA and is planned for up to two flights per year. The first Rodent Research flight, Rodent Research-1 (RR-1) validates the hardware and basic science operations (dissections and tissue preservation). Subsequent flights will add new capabilities to support rodent research on the ISS. RR-1 will validate the following capabilities: animal husbandry for up to 30 days, video downlink to support animal health checks and scientific analysis, on-orbit dissections, sample preservation in RNA. Later and formalin, sample transfer from formalin to ethanol (hindlimbs), rapid cool-down and subsequent freezing at -80 of tissues and carcasses, sample return and recovery. RR-2, scheduled for SpX-6 (Winter 20142015) will add the following capabilities: animal husbandry for up to 60 days, RFID chip reader for individual animal identification, water refill and food replenishment, anesthesia and recovery, bone densitometry, blood collection (via cardiac puncture), blood separation via centrifugation, soft tissue fixation in formalin with transfer to ethanol, and delivery of injectable drugs that require frozen storage prior to use. Additional capabilities are also planned for future flights and these include but are not limited to male mice, live animal return, and the development of experiment unique equipment to support science requirements for principal investigators that are selected for flight. In addition to the hardware capabilities to support rodent research the Crew Office has implemented a training program in generic rodent skills for all USOS crew members during their pre-assignment training rotation. This class includes training in general animal handling, euthanasia, injections, and dissections. The dissection portion of this training focuses on the dissection of the spleen, liver, kidney with adrenals, brain, eyes, and hindlimbs. By achieving and

Swim stress exaggerates the hyperactive mesocortical dopamine system in a rodent model of autism.

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Nakasato, Akane; Nakatani, Yasushi; Seki, Yoshinari; Tsujino, Naohisa; Umino, Masahiro; Arita, Hideho

2008-02-08

Several clinical reports have suggested that there is a hyperactivation of the dopaminergic system in people with autism. Using rats exposed prenatally to valproic acid (VPA) as an animal model of autism, we measured dopamine (DA) levels in samples collected from the frontal cortex (FC) using in vivo microdialysis and HPLC. The basal DA level in FC was significantly higher in VPA-exposed rats relative to controls. Since the mesocortical DA system is known to be sensitive to physical and psychological stressors, we measured DA levels in FC before, during, and after a 60-min forced swim test (FST). There were further gradual increases in FC DA levels during the FST in the VPA-exposed rats, but not in the control rats. Behavioral analysis during the last 10 min of the FST revealed a significant decrease in active, escape-oriented behavior and an increase in immobility, which is thought to reflect the development of depressive behavior that disengages the animal from active forms of coping with stressful stimuli. These results suggest that this rodent model of autism exhibits a hyperactive mesocortical DA system, which is exaggerated by swim stress. This abnormality may be responsible for depressive and withdrawal behavior observed in autism.

Spatial memory: Theoretical basis and comparative review on experimental methods in rodents.

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Paul, Carrillo-Mora; Magda, Giordano; Abel, Santamaría

2009-11-05

The assessment of learning and memory in animal models has been widely employed in scientific research for a long time. Among these models, those representing diseases with primary processes of affected memory - such as amnesia, dementia, brain aging, etc. - studies dealing with the toxic effects of specific drugs, and other exploring neurodevelopment, trauma, epilepsy and neuropsychiatric disorders, are often called on to employ these tools. There is a diversity of experimental methods assessing animal learning and memory skills. Overall, mazes are the devices mostly used today to test memory in rodents; there are several types of them, but their real usefulness, advantages and applications remain to be fully established and depend on the particular variant selected by the experimenter. The aims of the present article are first, to briefly review the accumulated knowledge in regard to spatial memory tasks; second, to bring the reader information on the different types of rodent mazes available to test spatial memory; and third, to elucidate the usefulness and limitations of each of these devices.

Glycoprotein 130 receptor signaling mediates α-cell dysfunction in a rodent model of type 2 diabetes

DEFF Research Database (Denmark)

Chow, Samuel Z; Speck, Madeleine; Yoganathan, Piriya

2014-01-01

Dysregulated glucagon secretion accompanies islet inflammation in type 2 diabetes. We recently discovered that interleukin (IL)-6 stimulates glucagon secretion from human and rodent islets. IL-6 family cytokines require the glycoprotein 130 (gp130) receptor to signal. In this study, we elucidated...

Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice

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Buckman, Laura B.; Thompson, Misty M.; Lippert, Rachel N.; Blackwell, Timothy S.; Yull, Fiona E.; Ellacott, Kate L.J.

2014-01-01

Objective Introduction of a high-fat diet to mice results in a period of voracious feeding, known as hyperphagia, before homeostatic mechanisms prevail to restore energy intake to an isocaloric level. Acute high-fat diet hyperphagia induces astrocyte activation in the rodent hypothalamus, suggesting a potential role of these cells in the homeostatic response to the diet. The objective of this study was to determine physiologic role of astrocytes in the acute homeostatic response to high-fat feeding. Methods We bred a transgenic mouse model with doxycycline-inducible inhibition of NFkappaB (NFκB) signaling in astrocytes to determine the effect of loss of NFκB-mediated astrocyte activation on acute high-fat hyperphagia. ELISA was used to measure the levels of markers of astrocyte activation, glial-fibrillary acidic protein (GFAP) and S100B, in the medial basal hypothalamus. Results Inhibition of NFκB signaling in astrocytes prevented acute high-fat diet-induced astrocyte activation and resulted in a 15% increase in caloric intake (P < 0.01) in the first 24 h after introduction of the diet. Conclusions These data reveal a novel homeostatic role for astrocytes in the acute physiologic regulation of food intake in response to high-fat feeding. PMID:25685690

Public health implications of changing rodent importation patterns— United States, 1999–2013

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Lankau, Emily W.; Sinclair, Julie R.; Schroeder, Betsy A.; Galland, G. Gale; Marano, Nina

2015-01-01

Summary The United States imports a large volume of live wild and domestic animal species; these animals pose a demonstrated risk for introduction of zoonotic diseases. Rodents are imported for multiple purposes, including scientific research, zoo exhibits, and the pet trade. Current U.S. public health regulatory restrictions specific to rodent importation pertain only to those of African origin. To understand the impacts of these regulations and the potential public health risks of international rodent trade to the United States, we evaluated live rodent import records during 1999 –2013 by shipment volume and geographic origin, source (e.g., wild -caught versus captive-or commercially bred), intended purpose, and rodent taxonomy. Live rodent imports increased from 2,737 animals during 1999 to 173,761 animals during 2013. Increases in both the number and size of shipments contributed to this trend. The proportion of wild-captured imports declined from 75% during 1999 to guinea pigs, and hamsters arriving from other countries in North America were predominant taxa underlying this trend . After 2003, African-origin imports became sporadic events under the federal permit process. These patterns suggest development of large -scale captive rodent breeding markets abroad for commercial sale in the United States. While the shift from wild-captured imports alleviates many conservation concerns and risks for novel disease emergence, such consolidated sourcing might elevate exposure risks for zoonotic diseases associated with high-density rodent breeding(e.g. , lymphocytic choriomeningitis or salmonellosis). A responsive border health system must periodically re-evaluate importation regulations in conjunction with key stakeholders to ensure a balance between the economic benefits of rodent trade against the potential public health risks. PMID:26245515

Tissue expander stimulated lengthening of arteries (TESLA) induces early endothelial cell proliferation in a novel rodent model.

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Potanos, Kristina; Fullington, Nora; Cauley, Ryan; Purcell, Patricia; Zurakowski, David; Fishman, Steven; Vakili, Khashayar; Kim, Heung Bae

2016-04-01

We examine the mechanism of aortic lengthening in a novel rodent model of tissue expander stimulated lengthening of arteries (TESLA). A rat model of TESLA was examined with a single stretch stimulus applied at the time of tissue expander insertion with evaluation of the aorta at 2, 4 and 7day time points. Measurements as well as histology and proliferation assays were performed and compared to sham controls. The aortic length was increased at all time points without histologic signs of tissue injury. Nuclear density remained unchanged despite the increase in length suggesting cellular hyperplasia. Cellular proliferation was confirmed in endothelial cell layer by Ki-67 stain. Aortic lengthening may be achieved using TESLA. The increase in aortic length can be achieved without tissue injury and results at least partially from cellular hyperplasia. Further studies are required to define the mechanisms involved in the growth of arteries under increased longitudinal stress. Copyright © 2015 Elsevier Inc. All rights reserved.

Harvesting behaviour of three central European rodents: Identifying the rodent pest in cereals

Czech Academy of Sciences Publication Activity Database

Heroldová, Marta; Tkadlec, Emil

2011-01-01

Roč. 30, č. 1 (2011), s. 82-84 ISSN 0261-2194 R&D Projects: GA MZe QH72075 Institutional research plan: CEZ:AV0Z60930519 Keywords : Apodemus sylvaticus * Apodemus uralensis * feeding behaviour * lab experiments * Microtus arvalis * rodent pest control Subject RIV: GF - Plant Pathology, Vermin, Weed, Plant Protection Impact factor: 1.402, year: 2011

Experimental sleep deprivation as a tool to test memory deficits in rodents

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VALERIA eCOLAVITO

2013-12-01

Full Text Available Paradigms of sleep deprivation (SD and memory testing in rodents (laboratory rats and mice are here reviewed. The vast majority of these studies have been aimed at understanding the contribution of sleep to cognition, and in particular to memory. Relatively little attention, instead, has been devoted to SD as a challenge to induce a transient memory impairment, and therefore as a tool to test cognitive enhancers in drug discovery. The purpose of this article is to provide an overview of the studies that have accurately described methodological aspects of the SD protocol and behavioral paradigm in order to critically assess them and propose SD protocols that could be employed as cognitive challenge. Total SD, partial or state-selective SD (rapid eye movement SD procedures are first reviewed, followed by procedures to investigate SD-induced impairment of learning and memory consolidation. Thus, a platform of knowledge is here provided for laboratory protocols that could be used to assess the efficacy of drugs designed to improve memory performance in rodents, including rodent models of neurodegenerative diseases that cause cognitive deficits, and Alzheimer’s disease in particular. Issues in the interpretation of such preclinical data and their predictive value for clinical translation are also discussed.

The response of human and rodent cells to hyperthermia

International Nuclear Information System (INIS)

Roizin-Towle, L.; Pirro, J.P.

1991-01-01

Inherent cellular radiosensitivity in vitro has been shown to be a good predictor of human tumor response in vivo. In contrast, the importance of the intrinsic thermosensitivity of normal and neoplastic human cells as a factor in the responsiveness of human tumors to adjuvant hyperthermia has never been analyzed systematically. A comparison of thermal sensitivity and thermo-radiosensitization in four rodent and eight human-derived cell lines was made in vitro. Arrhenius plots indicated that the rodent cells were more sensitive to heat killing than the human, and the break-point was 0.5 degrees C higher for the human than rodent cells. The relationship between thermal sensitivity and the interaction of heat with X rays at low doses was documented by thermal enhancement ratios (TER's). Cells received either a 1 hr exposure to 43 degrees C or a 20 minute treatment at 45 degrees C before exposure to 300 kVp X rays. Thermal enhancement ratios ranged from 1.0 to 2.7 for human cells heated at 43 degrees C and from 2.1 to 5.3 for heat exposures at 45 degrees C. Thermal enhancement ratios for rodent cells were generally 2 to 3 times higher than for human cells, because of the fact that the greater thermosensitivity of rodent cells results in a greater enhancement of radiation damage. Intrinsic thermosensitivity of human cells has relevance to the concept of thermal dose; intrinsic thermo-radiosensitization of a range of different tumor cells is useful in documenting the interactive effects of radiation combined with heat

Visual Landmarks Facilitate Rodent Spatial Navigation in Virtual Reality Environments

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Youngstrom, Isaac A.; Strowbridge, Ben W.

2012-01-01

Because many different sensory modalities contribute to spatial learning in rodents, it has been difficult to determine whether spatial navigation can be guided solely by visual cues. Rodents moving within physical environments with visual cues engage a variety of nonvisual sensory systems that cannot be easily inhibited without lesioning brain…

Impact of anesthesia, analgesia, and euthanasia technique on the inflammatory cytokine profile in a rodent model of severe burn injury.

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Al-Mousawi, Ahmed M; Kulp, Gabriela A; Branski, Ludwik K; Kraft, Robert; Mecott, Gabriel A; Williams, Felicia N; Herndon, David N; Jeschke, Marc G

2010-09-01

Anesthetics used in burn and trauma animal models may be influencing results by modulating inflammatory and acute-phase responses. Accordingly, we determined the effects of various anesthetics, analgesia, and euthanasia techniques in a rodent burn model. Isoflurane (ISO), ketamine-xylazine (KX), or pentobarbital (PEN) with or without buprenorphine were administered before scald-burn in 72 rats that were euthanized without anesthesia by decapitation after 24 h and compared with unburned shams. In a second experiment, 120 rats underwent the same scald-burn injury using KX, and 24 h later were euthanized under anesthesia or carbon dioxide (CO2). In addition, we compared euthanasia by exsanguination with that of decapitation. Serum cytokine levels were determined by an enzyme-linked immunosorbent assay. In the first experiment, ISO was associated with elevation of cytokine-induced neutrophil chemoattractant 2 (CINC-2) and monocyte chemotactic protein 1 (MCP-1), and KX and PEN was associated with elevation of CINC-1,CINC-2, IL-6, and MCP-1. Pentobarbital also decreased IL-1". IL-6 increased significantly when ISO or PEN were combined with buprenorphine. In the second experiment, euthanasia performed by exsanguination under ISO was associated with reduced levels of IL-1", CINC-1, CINC-2, and MCP-1, whereas KX reduced CINC-2 and increased IL-6 levels. Meanwhile, PEN reduced levels of IL-1" and MCP-1, and CO2 reduced CINC-2 and MCP-1. In addition,decapitation after KX, PEN, or CO2 decreased IL-1" and MCP-1, although we found no significant difference between ISO and controls. Euthanasia by exsanguination compared with decapitation using the same agent also led to modulation of several cytokines. Differential expression of inflammatory markers with the use of anesthetics and analgesics should be considered when designing animal studies and interpreting results because these seem to have a significant modulating impact. Our findings indicate that brief anesthesia with ISO

VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

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Carapau, Daniel; Pena, Ana C.; Ataíde, Ricardo; Monteiro, Carla A. A.; Félix, Nuno; Costa-Silva, Artur; Marinho, Claudio R. F.; Dias, Sérgio; Mota, Maria M.

2010-01-01

The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies. PMID:20502682

The Ethics of Rodent Control

NARCIS (Netherlands)

Meerburg, B.G.; Brom, F.W.A.; Kijlstra, A.

2008-01-01

Because western societies generally see animals as objects of moral concern, demands have been made on the way they are treated, e.g. during animal experimentation. In the case of rodent pests, however, inhumane control methods are often applied. This inconsistency in the human-animal relationship

ROLE OF THE MATERNAL ACUTE PHASE RESPONSE AND TUMOR NECROSIS FACTOR ALPHA IN THE DEVELOPMENTAL TOXICITY OF LIPOPOLYSACCHARIDE IN THE CD-1 MOUSE

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ABSTRACT The acute phase response (APR) functions to reset metabolic homeostasis following infectious, toxic or traumatic insult. TNF- , a putative mediator of the APR, has been associated with fetal death in rodents and preterm labor and delivery in humans. We hypothesized...

PAIN IN A PARKINSON`S DISEASE RODENT ANIMAL MODEL INDUCED WITH 6-HYDROXYDOPAMINE

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Antioch, I

2017-06-01

Full Text Available Pain phenomenon, the unpleasant sensory and emotional event, appears to evidently intrude in Parkinson disease (PD, a disease formally considered to be restricted only to motor deficits. Although over a half of persons with PD suffer from pain manifestations, there are very few reports targeting this issue. Considering the cases when motor symptoms of PD are eclipsed by severe pain disclosure, there is an obvious need of clarifying the intricate implications of pain in PD context. Because there are few studies researching the link between pain and PD in clinical context, but as well in animal models we chose to explore the effects of pain stimuli on a rodent model of PD. Materials and methods: We experimentally induced a PD model in Wistar rats (n=12 by injecting in the substantia nigra, a brain area known to be involved in PD occurrence, one dose of a 6-hydroxidopamine (6-OHDA solution (8µm 6-OHDA base and 4µm physiological saline, utilizing neurosurgery, while their control peers received same dose of saline solution. Two weeks after the intervention the animals were subjected to the hot-plate test, a behavioral task for acquiring pain sensitivity. Results: There was noticed a statistical significant (F(1,10 = 5.67, p=0.038 sensibility of the 6-OHDA rats to thermal pain stimuli (8.2 s ± 0.8 s in 6-OHDA group as compared to their peers (13.8 s ± 1.6 s in controls. Conclusions: The involvement of pain in PD animal models is demonstrated raising questions of how it influences PD evolution. Moreover, this result increases awareness of deficient diagnostic methods of pain in PD and as a consequence, poor treatment of pain manifestations.

New Development in NASA's Rodent Research Hardware for Conducting Long Duration Biomedical and Basic Research in Space

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Shirazi-Fard, Y.; Choi, S.; Harris, C.; Gong, C.; Beegle, J. E.; Stube, K. C.; Martin, K. J.; Nevitt, R. G.; Globus, R. G.

2017-01-01

Animal models, particularly rodents, are the foundation of pre-clinical research to understand human diseases and evaluate new therapeutics, and play a key role in advancing biomedical discoveries both on Earth and in space. The National Research Councils Decadal survey emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA Ames Research Center (ARC) to enhance science return for both commercial (CASIS) and government-sponsored rodent research. The Rodent Research program at NASA ARC has pioneered a new research capability on the International Space Station and has progressed toward translating research to the ISS utilizing commercial rockets, collaborating with academia and science industry, while training crewmembers to assist in performing research on orbit. Throughout phases of these missions, our practices, hardware and operations have evolved from tested to developed standards, and we are able to modify and customize our procedure and operations for mission specific requirements. The Rodent Research Habitat is capable of providing a living environment for animals on ISS according to standard animal welfare requirements. Using the cameras in the Habitat, the Rodent Research team has the ability to perform daily health checks on animals, and further analyze the collected videos for behavioral studies. A recent development of the Rodent Research hardware is inclusion of enrichment, to provide the animals the ability to rest and huddle. The Enrichment Hut is designed carefully for adult mice (up to 35 week old) within animal welfare, engineering, and operations constraints. The Hut is made out of the same stainless steel mesh as the cage interior, it has an ingress and an egress to allow animals move freely, and a hinge door to allow crewmembers remove the

Deep brain stimulation of the ventral hippocampus restores deficits in processing of auditory evoked potentials in a rodent developmental disruption model of schizophrenia.

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Ewing, Samuel G; Grace, Anthony A

2013-02-01

Existing antipsychotic drugs are most effective at treating the positive symptoms of schizophrenia but their relative efficacy is low and they are associated with considerable side effects. In this study deep brain stimulation of the ventral hippocampus was performed in a rodent model of schizophrenia (MAM-E17) in an attempt to alleviate one set of neurophysiological alterations observed in this disorder. Bipolar stimulating electrodes were fabricated and implanted, bilaterally, into the ventral hippocampus of rats. High frequency stimulation was delivered bilaterally via a custom-made stimulation device and both spectral analysis (power and coherence) of resting state local field potentials and amplitude of auditory evoked potential components during a standard inhibitory gating paradigm were examined. MAM rats exhibited alterations in specific components of the auditory evoked potential in the infralimbic cortex, the core of the nucleus accumbens, mediodorsal thalamic nucleus, and ventral hippocampus in the left hemisphere only. DBS was effective in reversing these evoked deficits in the infralimbic cortex and the mediodorsal thalamic nucleus of MAM-treated rats to levels similar to those observed in control animals. In contrast stimulation did not alter evoked potentials in control rats. No deficits or stimulation-induced alterations were observed in the prelimbic and orbitofrontal cortices, the shell of the nucleus accumbens or ventral tegmental area. These data indicate a normalization of deficits in generating auditory evoked potentials induced by a developmental disruption by acute high frequency, electrical stimulation of the ventral hippocampus. Copyright © 2012 Elsevier B.V. All rights reserved.

Experimental evidence of obesity as a risk factor for severe acute pancreatitis.

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Frossard, Jean-Louis; Lescuyer, Pierre; Pastor, Catherine M

2009-11-14

The incidence of acute pancreatitis, an inflammation of the pancreas, is increasing worldwide. Pancreatic injury is mild in 80%-90% of patients who recover without complications. The remaining patients may develop a severe disease with local complications such as acinar cell necrosis, abscess and remote organ injury including lung injury. The early prediction of the severity of the disease is an important goal for physicians in management of patients with acute pancreatitis in order to optimize the therapy and to prevent organ dysfunction and local complications. For that purpose, multiple clinical scale scores have been applied to patients with acute pancreatitis. Recently, a new problem has emerged: the increased severity of the disease in obese patients. However, the mechanisms by which obesity increases the severity of acute pancreatitis are unclear. Several hypotheses have been suggested: (1) obese patients have an increased inflammation within the pancreas; (2) obese patients have an increased accumulation of fat within and around the pancreas where necrosis is often located; (3) increase in both peri- and intra-pancreatic fat and inflammatory cells explain the high incidence of pancreatic inflammation and necrosis in obese patients; (4) hepatic dysfunction associated with obesity might enhance the systemic inflammatory response by altering the detoxification of inflammatory mediators; and (5) ventilation/perfusion mismatch leading to hypoxia associated with a low pancreatic flow might reduce the pancreatic oxygenation and further enhance pancreatic injury. Recent experimental investigations also show an increased mortality and morbidity in obese rodents with acute pancreatitis and the implication of the adipokines leptin and adiponectin. Such models are important to investigate whether the inflammatory response of the disease is enhanced by obesity. It is exciting to speculate that manipulation of the adipokine milieu has the potential to influence the

The water economy of South American desert rodents: from integrative to molecular physiological ecology.

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Bozinovic, Francisco; Gallardo, Pedro

2006-01-01

Rodents from arid and semi-arid habitats live under conditions where the spatial and temporal availability of free water is limited, or scarce, thus forcing these rodents to deal with the problem of water conservation. The response of rodents to unproductive desert environments and water deficits has been intensively investigated in many deserts of the world. However, current understanding of the cellular, systemic and organismal physiology of water economy relies heavily on short-term, laboratory-oriented experiments, which usually focus on responses at isolated levels of biological organization. In addition, studies in small South American mammals are scarce. Indeed xeric habitats have existed in South America for a long time and it is intriguing why present day South American desert rodents do not show the wide array of adaptive traits to desert life observed for rodents on other continents. Several authors have pointed out that South American desert rodents lack physiological and energetic specialization for energy and water conservation, hypothesizing that their success is based more on behavioral and ecological strategies. We review phenotypic flexibility and physiological diversity in water flux rate, urine osmolality, and expression of water channels in South American desert-dwelling rodents. As far as we know, this is the first review of integrative studies at cellular, systemic and organismal levels. Our main conclusion is that South American desert rodents possess structural as well as physiological systems for water conservation, which are as remarkable as those found in "classical" rodents inhabiting other desert areas of the world.

Helminth Infections of Rodents and Their Zoonotic Importance in Boyer-Ahmad District, Southwestern Iran

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Mohammad Javad RANJBAR

2017-12-01

Full Text Available AbstractBackground: Rodents are considered as reservoirs of various zoonotic diseases including helminthic infections. The current study aimed to evaluate the prevalence of helminth infections in rodents, in Boyer-Ahmad district, Southwestern Iran.Methods: Overall, 52 rodents were captured from various areas of the district by Sherman live traps. The animals were then euthanized and dissected. During necropsy, each organ was examined macroscopically for presence of any cyst or visible parasite. The gastrointestinal tract was removed and their contents were evaluated for larva or adult worms. Trichinella larvae in the rodents’ muscles were investigated by both digestion and pathological methods.Results: Twenty-eight (53.8% of the trapped rodents were male. The rodents were including 25 (48.1% Meriones persicus, 1(1.9% Calomyscus bailwardi, 1 (1.9% Arvicola terresterris, 7 (13.5% Rattus rattus, 8 (15.4% R. norvegicus, and 10 (19.2% Apodemus sylvaticus. Of them, 38 (73.0% were infected with at least one helminth. Collected rodents were infected with Hymenolepis diminuta (50%, Hymenolepis nana fraterna (28.8%, Skrjabinotaenia sp. (15.4%, Anoplocephalidae sp. (15.4%, Cysticercus fasciolaris (5.8%, Trichuris muris (36.5%, Aspiculuris tetraptera (15.4%, Syphacia sp. (5.7%, Rictularia sp. (15.4%, Trichostrongylus sp. (3.8%, and Gongylonema sp. (3.8%. M. persicus was the most (84% infected rodent, yet the differences between rodent genus and helminth infectivity were not statistically significant (P>0.05.Conclusion: The rodents in Boyer-Ahmad district are infected with different helminths infections that some of them are recognized as threat to human health.

Rodent Models of Non-classical Progesterone Action Regulating Ovulation

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Melinda A. Mittelman-Smith

2017-07-01

Full Text Available It is becoming clear that steroid hormones act not only by binding to nuclear receptors that associate with specific response elements in the nucleus but also by binding to receptors on the cell membrane. In this newly discovered manner, steroid hormones can initiate intracellular signaling cascades which elicit rapid effects such as release of internal calcium stores and activation of kinases. We have learned much about the translocation and signaling of steroid hormone receptors from investigations into estrogen receptor α, which can be trafficked to, and signal from, the cell membrane. It is now clear that progesterone (P4 can also elicit effects that cannot be exclusively explained by transcriptional changes. Similar to E2 and its receptors, P4 can initiate signaling at the cell membrane, both through progesterone receptor and via a host of newly discovered membrane receptors (e.g., membrane progesterone receptors, progesterone receptor membrane components. This review discusses the parallels between neurotransmitter-like E2 action and the more recently investigated non-classical P4 signaling, in the context of reproductive behaviors in the rodent.

Long-term Hyperglycemia Naturally Induces Dental Caries but Not Periodontal Disease in Type 1 and Type 2 Diabetic Rodents.

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Nakahara, Yutaka; Ozaki, Kiyokazu; Matsuura, Tetsuro

2017-11-01

Periodontal disease (PD) in patients with diabetes is described as the sixth complication of diabetes. We have previously shown that diabetes increases dental caries, and carious inflammation might have a strong effect on the adjacent periodontal tissue in diabetic rodent models. However, the possibility that hyperglycemia may induce PD in diabetic animals could not be completely eliminated. The goal of this study was to confirm the presence of PD in diabetic animal models by preventing carious inflammation with fluoride administration. F344 rats injected with alloxan (type 1 diabetic model) and db/db mice (type 2 diabetic model) were given either tap water alone or tap water containing fluoride. A cariostatic effect of fluoride was evident in the diabetic animals. Meanwhile, fluoride treatment drastically attenuated periodontal inflammation in addition to preventing dental caries. Furthermore, with fluoride treatment, periodontitis was notably nonexistent in the periodontal tissue surrounding the normal molars, whereas the caries-forming process was clearly observed in the teeth that were enveloped with persistent periodontitis, suggesting that enhanced periodontal inflammation might have been derived from the dental caries in the diabetic rodents rather than from the PD. In conclusion, long-term hyperglycemia naturally induces dental caries but not PD in type 1 and type 2 diabetic rodents. © 2017 by the American Diabetes Association.

Assessing the Diversity of Rodent-Borne Viruses: Exploring of High-Throughput Sequencing and Classical Amplification/Sequencing Approaches.

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Drewes, Stephan; Straková, Petra; Drexler, Jan F; Jacob, Jens; Ulrich, Rainer G

2017-01-01

Rodents are distributed throughout the world and interact with humans in many ways. They provide vital ecosystem services, some species are useful models in biomedical research and some are held as pet animals. However, many rodent species can have adverse effects such as damage to crops and stored produce, and they are of health concern because of the transmission of pathogens to humans and livestock. The first rodent viruses were discovered by isolation approaches and resulted in break-through knowledge in immunology, molecular and cell biology, and cancer research. In addition to rodent-specific viruses, rodent-borne viruses are causing a large number of zoonotic diseases. Most prominent examples are reemerging outbreaks of human hemorrhagic fever disease cases caused by arena- and hantaviruses. In addition, rodents are reservoirs for vector-borne pathogens, such as tick-borne encephalitis virus and Borrelia spp., and may carry human pathogenic agents, but likely are not involved in their transmission to human. In our days, next-generation sequencing or high-throughput sequencing (HTS) is revolutionizing the speed of the discovery of novel viruses, but other molecular approaches, such as generic RT-PCR/PCR and rolling circle amplification techniques, contribute significantly to the rapidly ongoing process. However, the current knowledge still represents only the tip of the iceberg, when comparing the known human viruses to those known for rodents, the mammalian taxon with the largest species number. The diagnostic potential of HTS-based metagenomic approaches is illustrated by their use in the discovery and complete genome determination of novel borna- and adenoviruses as causative disease agents in squirrels. In conclusion, HTS, in combination with conventional RT-PCR/PCR-based approaches, resulted in a drastically increased knowledge of the diversity of rodent viruses. Future improvements of the used workflows, including bioinformatics analysis, will further

Stress, social behavior, and resilience: Insights from rodents

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Beery, Annaliese K.; Kaufer, Daniela

2014-01-01

The neurobiology of stress and the neurobiology of social behavior are deeply intertwined. The social environment interacts with stress on almost every front: social interactions can be potent stressors; they can buffer the response to an external stressor; and social behavior often changes in response to stressful life experience. This review explores mechanistic and behavioral links between stress, anxiety, resilience, and social behavior in rodents, with particular attention to different social contexts. We consider variation between several different rodent species and make connections to research on humans and non-human primates. PMID:25562050

Optical coherence tomography based microangiography for quantitative monitoring of structural and vascular changes in a rat model of acute uveitis in vivo: a preliminary study

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Choi, Woo June; Pepple, Kathryn L.; Zhi, Zhongwei; Wang, Ruikang K.

2015-01-01

Uveitis models in rodents are important in the investigation of pathogenesis in human uveitis and the development of appropriate therapeutic strategies for treatment. Quantitative monitoring of ocular inflammation in small animal models provides an objective metric to assess uveitis progression and/or therapeutic effects. We present a new application of optical coherence tomography (OCT) and OCT-based microangiography (OMAG) to a rat model of acute anterior uveitis induced by intravitreal injection of a killed mycobacterial extract. OCT/OMAG is used to provide noninvasive three-dimensional imaging of the anterior segment of the eyes prior to injection (baseline) and two days post-injection (peak inflammation) in rats with and without steroid treatments. OCT imaging identifies characteristic structural and vascular changes in the anterior segment of the inflamed animals when compared to baseline images. Characteristics of inflammation identified include anterior chamber cells, corneal edema, pupillary membranes, and iris vasodilation. In contrast, no significant difference from the control is observed for the steroid-treated eye. These findings are compared with the histology assessment of the same eyes. In addition, quantitative measurements of central corneal thickness and iris vessel diameter are determined. This pilot study demonstrates that OCT-based microangiography promises to be a useful tool for the assessment and management of uveitis in vivo.

Contrasting Patterns in Mammal–Bacteria Coevolution: Bartonella and Leptospira in Bats and Rodents

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Lei, Bonnie R.; Olival, Kevin J.

2014-01-01

Background Emerging bacterial zoonoses in bats and rodents remain relatively understudied. We conduct the first comparative host–pathogen coevolutionary analyses of bacterial pathogens in these hosts, using Bartonella spp. and Leptospira spp. as a model. Methodology/Principal Findings We used published genetic data for 51 Bartonella genotypes from 24 bat species, 129 Bartonella from 38 rodents, and 26 Leptospira from 20 bats. We generated maximum likelihood and Bayesian phylogenies for hosts and bacteria, and tested for coevoutionary congruence using programs ParaFit, PACO, and Jane. Bartonella spp. and their bat hosts had a significant coevolutionary fit (ParaFitGlobal = 1.9703, P≤0.001; m2 global value = 7.3320, P≤0.0001). Bartonella spp. and rodent hosts also indicated strong overall patterns of cospeciation (ParaFitGlobal = 102.4409, P≤0.001; m2 global value = 86.532, P≤0.0001). In contrast, we were unable to reject independence of speciation events in Leptospira and bats (ParaFitGlobal = 0.0042, P = 0.84; m2 global value = 4.6310, P = 0.5629). Separate analyses of New World and Old World data subsets yielded results congruent with analysis from entire datasets. We also conducted event-based cophylogeny analyses to reconstruct likely evolutionary histories for each group of pathogens and hosts. Leptospira and bats had the greatest number of host switches per parasite (0.731), while Bartonella and rodents had the fewest (0.264). Conclusions/Significance In both bat and rodent hosts, Bartonella exhibits significant coevolution with minimal host switching, while Leptospira in bats lacks evolutionary congruence with its host and has high number of host switches. Reasons underlying these variable coevolutionary patterns in host range are likely due to differences in disease-specific transmission and host ecology. Understanding the coevolutionary patterns and frequency of host-switching events between bacterial pathogens and

Research Note. Occurrence of gastrointestinal helminths in commensal rodents from Tabasco, Mexico

OpenAIRE

Cigarroa-Toledo N.; Santos-Martinez Y. De Los; Zaragoza-Vera C. V.; Garcia-Rodriguez M. M.; Baak-Baak C. M.; Machain-Williams C.; Garcia-Rejon J. E.; Panti-May J. A.; Torres-Chable O. M.

2017-01-01

The aim of this study was to determine the prevalence and species composition of helminths in commensal rodents captured inside private residences in the city of Villahermosa in Tabasco, Mexico. Trapping was performed at each house for three consecutive nights from October to December 2015. Fifty commensal rodents were captured: 23 Rattus norvegicus, 16 Mus musculus and 11 Rattus rattus. Rodents were transported alive to the laboratory and held in cages until they defecated. Feces were analyz...

Glibenclamide for the Treatment of Acute CNS Injury

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J. Marc Simard

2013-10-01

Full Text Available First introduced into clinical practice in 1969, glibenclamide (US adopted name, glyburide is known best for its use in the treatment of diabetes mellitus type 2, where it is used to promote the release of insulin by blocking pancreatic KATP [sulfonylurea receptor 1 (Sur1-Kir6.2] channels. During the last decade, glibenclamide has received renewed attention due to its pleiotropic protective effects in acute CNS injury. Acting via inhibition of the recently characterized Sur1-Trpm4 channel (formerly, the Sur1-regulated NCCa-ATP channel and, in some cases, via brain KATP channels, glibenclamide has been shown to be beneficial in several clinically relevant rodent models of ischemic and hemorrhagic stroke, traumatic brain injury, spinal cord injury, neonatal encephalopathy of prematurity, and metastatic brain tumor. Glibenclamide acts on microvessels to reduce edema formation and secondary hemorrhage, it inhibits necrotic cell death, it exerts potent anti-inflammatory effects and it promotes neurogenesis—all via inhibition of Sur1. Two clinical trials, one in TBI and one in stroke, currently are underway. These recent findings, which implicate Sur1 in a number of acute pathological conditions involving the CNS, present new opportunities to use glibenclamide, a well-known, safe pharmaceutical agent, for medical conditions that heretofore had few or no treatment options.

Wild rodents (Dipodomys merriami) used as biomonitors in contaminated mining sites.

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Espinosa-Reyes, Guillermo; Torres-Dosal, Arturo; Ilizaliturri, Cesar; Gonzalez-Mille, Donaji; Diaz-Barriga, Fernando; Mejia-Saavedra, Jesus

2010-01-01

Mining is one of the most important industrial activities globally; however, mining processes have critical environmental impacts, as mining is a major source of metals and metalloids that contribute significantly to the pollution of soil, sediment, water and air. Heavy metals can impact the health of exposed human populations and nonhuman receptors. This study focused on arsenic because its genotoxicity is well-known. Previously, we proposed a methodology to evaluate and integrate risk from a single source affecting different biologic receptors. Here, we propose an alternative approach estimating arsenic exposure in children and kangaroo rats using probabilistic simulation with Monte Carlo modeling. The estimates are then associated to measured DNA damage and compared to both populations of children and rodents living in contaminated and in reference areas. Finally, based on the integrated analysis of the generated information, we evaluate the potential use of wild rodents (Dipodomys merriami) as a biomonitor at mining sites. Results indicate that the variation of genotoxicity in children of the reference site is approximately 2 units when compared to the children of the contaminated site. In the rodents we observed a variation of approximately 4 units between those of the reference site when compared to those living on the contaminated site. We propose that D. merriami can be used as a biomonitor organism in sites with mining activity, and that a non-lethal test can be used to evaluate risk from metal exposure.

Comparison of food hoarding of two sympatric rodent species under interspecific competition.

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Zhang, Yi-Feng; Tong, Lei; Ji, Wei-Hong; Lu, Ji-Qi

2013-01-01

Competition can greatly affect the food hoarding strategies of rodents and the fate of seeds hoarded. In order to understand the influence of interspecific competition on food caching behavior of sympatric rodents, we investigated food hoarding patterns of two sympatric rodent species, buff-breasted rat (Rattus flavipectus) and Chinese white-bellied rat (Niviventor confucianus), and compared their responses and adjustment in hoarding behavior under interspecific competition. The results showed that: (1) the buff-breasted rat larder hoarded seeds only, while Chinese white-bellied rat hoarded seeds in both larder and scatter forms; (2) two species of rodents both larder hoarded more seeds when competitors were present; and (3) the Chinese white-bellied rats adjusted their seed hoarding from scatter to larder when competitors were introduced, which reduced the seed availability. Therefore, we concluded that rodents would adjust their food hoarding strategy when interspecific competitors were present, and this may produce a different effect on the fate of seeds and the recruitment of plants. This article is part of a Special Issue entitled: insert SI title. Copyright © 2012. Published by Elsevier B.V.

Navigating to new frontiers in behavioral neuroscience: Traditional neuropsychological tests predict human performance on a rodent-inspired radial-arm maze

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Sarah E. Mennenga

2014-09-01

Full Text Available We constructed an 11-arm, walk-through, human radial-arm maze (HRAM as a translational instrument to compare existing methodology in the areas of rodent and human learning and memory research. The HRAM, utilized here, serves as an intermediary test between the classic rat radial-arm maze (RAM and standard human neuropsychological and cognitive tests. We show that the HRAM is a useful instrument to examine working memory ability, explore the relationships between rodent and human memory and cognition models, and evaluate factors that contribute to human navigational ability. One-hundred-and-fifty-seven participants were tested on the HRAM, and scores were compared to performance on a standard cognitive battery focused on episodic memory, working memory capacity, and visuospatial ability. We found that errors on the HRAM increased as working memory demand became elevated, similar to the pattern typically seen in rodents, and that for this task, performance appears similar to Miller’s classic description of human working memory capacity of 7±2 items. Regression analysis revealed that measures of working memory capacity and visuospatial ability accounted for a large proportion of variance in HRAM scores, while measures of episodic memory and general intelligence did not serve as significant predictors of HRAM performance. We present the HRAM as a novel instrument for measuring navigational behavior in humans, as is traditionally done in basic science studies evaluating rodent learning and memory, thus providing a useful tool to help connect and translate between human and rodent models of cognitive functioning.

Tick parasites of rodents in Romania: host preferences, community structure and geographical distribution.

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Mihalca, Andrei D; Dumitrache, Mirabela O; Sándor, Attila D; Magdaş, Cristian; Oltean, Miruna; Györke, Adriana; Matei, Ioana A; Ionică, Angela; D'Amico, Gianluca; Cozma, Vasile; Gherman, Călin M

2012-11-21

Ticks are among the most important vectors of zoonotic diseases in temperate regions of Europe, with widespread distribution and high densities, posing an important medical risk. Most ticks feed on a variety of progressively larger hosts, with a large number of small mammal species typically harbouring primarily the immature stages. However, there are certain Ixodidae that characteristically attack micromammals also during their adult stage. Rodents are widespread hosts of ticks, important vectors and competent reservoirs of tick-borne pathogens. Micromammal-tick associations have been poorly studied in Romania, and our manuscript shows the results of a large scale study on tick infestation epidemiology in rodents from Romania. Rodents were caught using snap-traps in a variety of habitats in Romania, between May 2010 and November 2011. Ticks were individually collected from these rodents and identified to species and development stage. Frequency, mean intensity, prevalence and its 95% confidence intervals were calculated using the EpiInfo 2000 software. A p value of Romania for the presence of ticks. Each collected tick was identified to species level and the following epidemiological parameters were calculated: prevalence, mean intensity and mean abundance. The total number of ticks collected from rodents was 483, with eight species identified: Ixodes ricinus, I. redikorzevi, I. apronophorus, I. trianguliceps, I. laguri, Dermacentor marginatus, Rhipicephalus sanguineus and Haemaphysalis sulcata. The overall prevalence of tick infestation was 29.55%, with a mean intensity of 3.86 and a mean abundance of 1.14. Only two polyspecific infestations were found: I. ricinus + I. redikorzevi and I. ricinus + D. marginatus. Our study showed a relatively high diversity of ticks parasitizing rodents in Romania. The most common tick in rodents was I. ricinus, followed by I. redikorzevi. Certain rodents seem to host a significantly higher number of tick species than others, the

The need to implement the landscape of fear within rodent pest management strategies.

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Krijger, Inge M; Belmain, Steven R; Singleton, Grant R; Groot Koerkamp, Peter Wg; Meerburg, Bastiaan G

2017-12-01

Current reactive pest management methods have serious drawbacks such as the heavy reliance on chemicals, emerging genetic rodenticide resistance and high secondary exposure risks. Rodent control needs to be based on pest species ecology and ethology to facilitate the development of ecologically based rodent management (EBRM). An important aspect of EBRM is a strong understanding of rodent pest species ecology, behaviour and spatiotemporal factors. Gaining insight into the behaviour of pest species is a key aspect of EBRM. The landscape of fear (LOF) is a mapping of the spatial variation in the foraging cost arising from the risk of predation, and reflects the levels of fear a prey species perceives at different locations within its home range. In practice, the LOF maps habitat use as a result of perceived fear, which shows where bait or traps are most likely to be encountered and used by rodents. Several studies have linked perceived predation risk of foraging animals with quitting-harvest rates or giving-up densities (GUDs). GUDs have been used to reflect foraging behaviour strategies of predator avoidance, but to our knowledge very few papers have directly used GUDs in relation to pest management strategies. An opportunity for rodent control strategies lies in the integration of the LOF of rodents in EBRM methodologies. Rodent management could be more efficient and effective by concentrating on those areas where rodents perceive the least levels of predation risk. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Why can't rodents vomit? A comparative behavioral, anatomical, and physiological study.

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Charles C Horn

Full Text Available The vomiting (emetic reflex is documented in numerous mammalian species, including primates and carnivores, yet laboratory rats and mice appear to lack this response. It is unclear whether these rodents do not vomit because of anatomical constraints (e.g., a relatively long abdominal esophagus or lack of key neural circuits. Moreover, it is unknown whether laboratory rodents are representative of Rodentia with regards to this reflex. Here we conducted behavioral testing of members of all three major groups of Rodentia; mouse-related (rat, mouse, vole, beaver, Ctenohystrica (guinea pig, nutria, and squirrel-related (mountain beaver species. Prototypical emetic agents, apomorphine (sc, veratrine (sc, and copper sulfate (ig, failed to produce either retching or vomiting in these species (although other behavioral effects, e.g., locomotion, were noted. These rodents also had anatomical constraints, which could limit the efficiency of vomiting should it be attempted, including reduced muscularity of the diaphragm and stomach geometry that is not well structured for moving contents towards the esophagus compared to species that can vomit (cat, ferret, and musk shrew. Lastly, an in situ brainstem preparation was used to make sensitive measures of mouth, esophagus, and shoulder muscular movements, and phrenic nerve activity-key features of emetic episodes. Laboratory mice and rats failed to display any of the common coordinated actions of these indices after typical emetic stimulation (resiniferatoxin and vagal afferent stimulation compared to musk shrews. Overall the results suggest that the inability to vomit is a general property of Rodentia and that an absent brainstem neurological component is the most likely cause. The implications of these findings for the utility of rodents as models in the area of emesis research are discussed.

Stress as a one-armed bandit: Differential effects of stress paradigms on the morphology, neurochemistry and behavior in the rodent amygdala

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Marlene A. Wilson

2015-01-01

Full Text Available Neuroplasticity may be defined as the ability of the central nervous system (CNS to respond to changes in the internal and external environment and it is well established that some stimuli have the ability to facilitate or impair neuroplasticity depending on the pre-existing milieu. A classic example of a stimulus that can both facilitate and impair neuroplasticity is stress. Indeed, the ability of CNS to respond to acute stress is often dependent upon the prior stress history of the individual. While responses to acute stress are often viewed as adaptive in nature, stress reactivity in subjects with prior chronic stress experiences are often linked to neuropsychiatric disorders, including major depressive disorder, post-traumatic stress disorder (PTSD and anxiety. In rodent studies, chronic stress exposure produces structural and functional alterations in the hippocampus and medial prefrontal cortex that are consistent across different types of stress paradigms. Conversely, the amygdala appears to exhibit differential structural and functional responses to stress that are dependent on a variety of factors, including the type of stressor performed and the duration of the stress paradigm. This is most evident in output measures including morphological analysis of amygdala neurons, measurement of glutamatergic tone in amygdalar subdivisions and the analysis of amygdala-centric behaviors. Accordingly, this review will provide an overview of the effects of stress on the structural and functional plasticity of the rodent amygdala, especially in relation to the differential effects of repeated or chronic stress paradigms on dendritic architecture, neurochemistry of the glutamatergic system and behavior.

Stress as a one-armed bandit: Differential effects of stress paradigms on the morphology, neurochemistry and behavior in the rodent amygdala

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Wilson, Marlene A.; Grillo, Claudia A.; Fadel, Jim R.; Reagan, Lawrence P.

2015-01-01

Neuroplasticity may be defined as the ability of the central nervous system (CNS) to respond to changes in the internal and external environment and it is well established that some stimuli have the ability to facilitate or impair neuroplasticity depending on the pre-existing milieu. A classic example of a stimulus that can both facilitate and impair neuroplasticity is stress. Indeed, the ability of CNS to respond to acute stress is often dependent upon the prior stress history of the individual. While responses to acute stress are often viewed as adaptive in nature, stress reactivity in subjects with prior chronic stress experiences are often linked to neuropsychiatric disorders, including major depressive disorder, post-traumatic stress disorder (PTSD) and anxiety. In rodent studies, chronic stress exposure produces structural and functional alterations in the hippocampus and medial prefrontal cortex that are consistent across different types of stress paradigms. Conversely, the amygdala appears to exhibit differential structural and functional responses to stress that are dependent on a variety of factors, including the type of stressor performed and the duration of the stress paradigm. This is most evident in output measures including morphological analysis of amygdala neurons, measurement of glutamatergic tone in amygdalar subdivisions and the analysis of amygdala-centric behaviors. Accordingly, this review will provide an overview of the effects of stress on the structural and functional plasticity of the rodent amygdala, especially in relation to the differential effects of repeated or chronic stress paradigms on dendritic architecture, neurochemistry of the glutamatergic system and behavior. PMID:26844236

Zoonotic pathogens in Atlantic Forest wild rodents in Brazil: Bartonella and Coxiella infections.

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Rozental, Tatiana; Ferreira, Michelle Santos; Guterres, Alexandro; Mares-Guia, Maria Angélica; Teixeira, Bernardo R; Gonçalves, Jonathan; Bonvicino, Cibele Rodrigues; D'Andrea, Paulo Sergio; de Lemos, Elba Regina Sampaio

2017-04-01

Zoonotic pathogens comprise a significant and increasing fraction of all emerging and re-emerging infectious diseases that plague humans. Identifying host species is one of the keys to controlling emerging infectious diseases. From March 2007 until April 2012, we collected a total of 131 wild rodents in eight municipalities of Rio de Janeiro, Brazil. We investigated these rodents for infection with Coxiella burnetii, Bartonella spp. and Rickettsia spp. In total, 22.1% (29/131) of the rodents were infected by at least one pathogen; co-infection was detected in 1.5% (2/131) of rodents. Coxiella burnetii was detected in 4.6% (6/131) of the wild animals, 17.6% of the rodents harbored Bartonella spp. No cases of Rickettsia were identified. Bartonella doshiae and Bartonella vinsonii were the species found on the wild mammals. This report is the first to note C. burnetii, B. doshiae and B. vinsonii natural infections in Atlantic Forest wild rodents in Brazil. Our work highlights the potential risk of transmission to humans, since most of the infected specimens belong to generalist species that live near human dwellings. Copyright © 2017 Elsevier B.V. All rights reserved.

An in-vitro–in-vivo model for the transdermal delivery of cholecalciferol for the purposes of rodent management

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Davies, J.; Ingham, A.

2015-01-01

The natural selection of anticoagulant resistant rats has resulted in a need for an alternative to anticoagulant rodenticides which differs in both active ingredient and in the method of dosing. Cholecalciferol toxicity to rodents using the dermal route is demonstrated using a variety of penetration enhancing formulations in two in-vitro models and finally in-vivo. A 1 ml dose of 50/50 (v/v) DMSO/ethanol containing 15% (v/v) PEG 200 and 20% (w/v) cholecalciferol was judged as ‘sufficiently effective’ in line with the European Union’s Biocidal Products Regulation (No. 528/2012) during in-vivo studies. This dose was found to cause 100% mortality in a rat population in 64.4 h (±22 h). PMID:25835266

A New Variational Method for Bias Correction and Its Applications to Rodent Brain Extraction.

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Chang, Huibin; Huang, Weimin; Wu, Chunlin; Huang, Su; Guan, Cuntai; Sekar, Sakthivel; Bhakoo, Kishore Kumar; Duan, Yuping

2017-03-01

Brain extraction is an important preprocessing step for further analysis of brain MR images. Significant intensity inhomogeneity can be observed in rodent brain images due to the high-field MRI technique. Unlike most existing brain extraction methods that require bias corrected MRI, we present a high-order and L 0 regularized variational model for bias correction and brain extraction. The model is composed of a data fitting term, a piecewise constant regularization and a smooth regularization, which is constructed on a 3-D formulation for medical images with anisotropic voxel sizes. We propose an efficient multi-resolution algorithm for fast computation. At each resolution layer, we solve an alternating direction scheme, all subproblems of which have the closed-form solutions. The method is tested on three T2 weighted acquisition configurations comprising a total of 50 rodent brain volumes, which are with the acquisition field strengths of 4.7 Tesla, 9.4 Tesla and 17.6 Tesla, respectively. On one hand, we compare the results of bias correction with N3 and N4 in terms of the coefficient of variations on 20 different tissues of rodent brain. On the other hand, the results of brain extraction are compared against manually segmented gold standards, BET, BSE and 3-D PCNN based on a number of metrics. With the high accuracy and efficiency, our proposed method can facilitate automatic processing of large-scale brain studies.

Guide to Commensal Rodent Control

Science.gov (United States)

1991-12-01

in many detergents also fluoresce. For positive identification, place the suspect material on Urease Siom lhymol Blue test paper, moisten with water...are applied in a thin layer in protected rat and mouse r’unways, baitboxes, or tubes along walls. The powder is picked up by the rodents on their feet

Occurrence and distribution of Giardia species in wild rodents in Germany.

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Helmy, Yosra A; Spierling, Nastasja G; Schmidt, Sabrina; Rosenfeld, Ulrike M; Reil, Daniela; Imholt, Christian; Jacob, Jens; Ulrich, Rainer G; Aebischer, Toni; Klotz, Christian

2018-03-27

Giardiasis is an important gastrointestinal parasitic disease in humans and other mammals caused by the protozoan Giardia duodenalis. This species complex is represented by genetically distinct groups (assemblages A-H) with varying zoonotic potential and host preferences. Wild rodents can harbor potentially zoonotic assemblages A and B, and the rodent-specific assemblage G. Other Giardia spp. found in these animals are Giardia muris and Giardia microti. For the latter, only limited information on genetic typing is available. It has been speculated that wild rodents might represent an important reservoir for parasites causing human giardiasis. The aim of this study was to investigate the occurrence and distribution of Giardia spp. and assemblage types in wild rodents from different study sites in Germany. Screening of 577 wild rodents of the genera Apodemus, Microtus and Myodes, sampled at eleven study sites in Germany, revealed a high overall Giardia prevalence. Giardia species determination at the SSU rDNA gene locus revealed that Apodemus mice, depending on species, were predominantly infected with one of two distinct G. muris sequence types. Giardia microti was the predominant parasite species found in voles of the genera Microtus and Myodes. Only a few animals were positive for potentially zoonotic G. duodenalis. Subtyping at the beta-giardin (bg) and glutamine dehydrogenase (gdh) genes strongly supported the existence of different phylogenetic subgroups of G. microti that are preferentially harbored by distinct host species. The present study highlights the preference of G. muris for Apodemus, and G. microti for Microtus and Myodes hosts and argues for a very low prevalence of zoonotic G. duodenalis assemblages in wild rodents in Germany. It also provides evidence that G. muris and G. microti subdivide into several phylogenetically distinguishable subgroups, each of which appears to be preferentially harbored by species of a particular rodent host genus

Modeling specific phobias and posttraumatic stress disorder in rodents: the challenge to convey both cognitive and emotional features.

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Berardi, Andrea; Trezza, Viviana; Campolongo, Campolongo

2012-01-01

Aberrant emotional memory processing is a core, disabling feature of both specific phobias and posttraumatic stress disorder (PTSD), two psychiatric diseases of significant prevalence and morbidity whose cognitive symptoms cannot be adequately treated by current psychopharmacological tools. Elucidating the neurobiological mechanisms involved in the etiology of these diseases is of great interest for the identification of new therapeutics that improve not only the symptomatology but also the full recovery from the pathology. To this aim, several animal models have been proposed based on substantial resemblance between the behavioral alterations seen in animals and the human pathology. The purpose of this review is to describe and comment on the most commonly used rodent models of specific phobias and PTSD. A particular focus will be reserved to the cued version of fear conditioning, as the highly specific stimulus-bound conditioned fear response seems to fit well with clinical descriptions of phobic fear.Moreover, animal models of PTSD will be evaluated by referring to three elements that are considered essential ina valid model of this disease: stressor exposure, memory for the stressor, and anxiety-related behaviors. Finally, current therapeutic directions, with a focus on cannabinoid and glucocorticoid compounds, will be briefly outlined.

Domestic cats and dogs create a landscape of fear for pest rodents around rural homesteads.

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Themb'alilahlwa A M Mahlaba

Full Text Available Using domestic predators such as cats to control rodent pest problems around farms and homesteads is common across the world. However, practical scientific evidence on the impact of such biological control in agricultural settings is often lacking. We tested whether the presence of domestic cats and/or dogs in rural homesteads would affect the foraging behaviour of pest rodents. We estimated giving up densities (GUDs from established feeding patches and estimated relative rodent activity using tracking tiles at 40 homesteads across four agricultural communities. We found that the presence of cats and dogs at the same homestead significantly reduced activity and increased GUDs (i.e. increased perception of foraging cost of pest rodent species. However, if only cats or dogs alone were present at the homestead there was no observed difference in rodent foraging activity in comparison to homesteads with no cats or dogs. Our results suggest that pest rodent activity can be discouraged through the presence of domestic predators. When different types of predator are present together they likely create a heightened landscape of fear for foraging rodents.

Protozoan Parasites of Rodents and Their Zoonotic Significance in Boyer-Ahmad District, Southwestern Iran

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Zeinab Seifollahi

2016-01-01

Full Text Available Backgrounds. Wild rodents are reservoirs of various zoonotic diseases, such as toxoplasmosis, babesiosis, and leishmaniasis. The current study aimed to assess the protozoan infection of rodents in Boyer-Ahmad district, southwestern Iran. Materials and Methods. A total of 52 rodents were collected from different parts of Boyer-Ahmad district, in Kohgiluyeh and Boyer-Ahmad province, using Sherman live traps. Each rodent was anesthetized with ether, according to the ethics of working with animals, and was dissected. Samples were taken from various tissues and stool samples were collected from the contents of the colon and small intestines. Moreover, 2 to 5 mL of blood was taken from each of the rodents and the sera were examined for anti-Leishmania antibodies, by ELISA, or anti-T. gondii antibodies, by modified agglutination test (MAT. DNA was extracted from brain tissue samples of each rodent and PCR was used to identify the DNA of T. gondii. Results. Of the 52 stool samples of rodents studied by parasitological methods, intestinal protozoa infection was seen in 28 cases (53.8%. From 52 rodents, 19 (36.5% were infected with Trichomonas, 10 (19.2% with Giardia muris, and 11 (21.2% with Entamoeba spp. Also, 10 cases (19.2% were infected with Blastocystis, 3 (5.8% were infected with Chilomastix, 7 (13.5% were infected with Endolimax, 1 (1.9% was infected with Retortamonas, 3 (5.77% were infected with T. gondii, and 6 (11.54% were infected with Trypanosoma lewisi. Antibodies to T. gondii were detected in the sera of 5 (9.61% cases. Results of the molecular study showed T. gondii infection in 3 (5.77% of the rodents. Findings of this study showed that rodents in Kohgiluyeh and Boyer-Ahmad province, southwestern Iran, are infected with several blood and intestinal parasites; some of them might be potential risks to residents and domestic animals in the region.

Population response of rodents to control with rodenticides

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A.V. TCHABOVSKY

2009-04-01

Full Text Available We summarize theoretical approaches and practice of rodent pest control in Russia and former USSR during last 50 years. We review literature as well as original data to understand mechanisms of rodent populations recovery after chemical control campaigns in urban areas, agricultural lands and natural foci of plague. Laboratory and field experiments indicate that inherent individual variation in behavioural, physiological and life-history traits provides survival of heterogeneous mix of individuals in residual population with increased resistance to poisonous baits and high reproductive potential that leads to fast recovery of a population. In a series of field experiments with various rodent and lagomorph species (Mus musculus, Rattus norvegicus, Meriones unguiculatus, M.meridianus, M.tamariscinus, Ochotona pallasii we have shown that patterns of recolonization of depopulated area and mechanisms of population recovery vary among species and depend on species-specific social organization. After control territorial and group-living species demonstrated an increase in mobility and affiliative and marking behaviour and a decrease in intraspecific aggression. The rate of recolonization of treated areas was high due to redistribution of survived individuals and immigration by neighbors. Population recovered to original level due to increased breeding performance and fecundity of both survived residents and immigrants. In contrast, socially-independent species exhibited minor changes in behaviour. Recolonization was mainly due to better survival and recruitment of youngs, so the rate of recolonization was low. Species-specificity of behavioural compensation mechanisms to control should be considered when developing ecologically based rodent management strategies.

an ecological study on rodents of natural vegetation and farm lands ...

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habitat association of rodents was conducted in Siltie natural vegetation and nearby farmlands ... In each habitat type, one representative grid was selected for live trapping. In addition, rodents were also snap- trapped from these habitats. A total of 562 captures was made .... into seeds, leaves, roots, earthworms and arthro-.

Small rodents as paratenic or intermediate hosts of carnivore parasites in Berlin, Germany.

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Krücken, Jürgen; Blümke, Julia; Maaz, Denny; Demeler, Janina; Ramünke, Sabrina; Antolová, Daniela; Schaper, Roland; von Samson-Himmelstjerna, Georg

2017-01-01

Rodents are important intermediate and paratenic hosts for carnivore parasites, including the important zoonotic agents Toxoplasma, Echinococcus and Toxocara. Monitoring of such parasites in rodents can be used to detect increasing risks for human and veterinary public health. Rodents were trapped at four sites in Berlin, two near the city center, two at the periphery. PCRs were conducted to detect Coccidia (target ITS-1) and specifically Toxoplasma gondii (repetitive element) in brain and ascarids (ITS-2) in muscle or brain tissue. During necropsies, metacestodes were collected and identified using ITS-2 and 12S rRNA PCRs. An ELISA to detect antibodies against Toxocara canis ES antigens was performed. Within the 257 examined rodents, the most frequently observed parasite was Frenkelia glareoli predominantly found in Myodes glareolus. T. gondii was only detected in 12 rodents and Microtus spp. (although strongly underrepresented) had a significantly increased chance of being positive. Neither Echinococcus nor typical Taenia parasites of dogs and cats were found but Mesocestoides litteratus and Taenia martis metacestodes were identified which can cause severe peritoneal or ocular cysticercosis in dogs, primates and humans. Using PCR, the ascarids T. canis (n = 8), Toxocara cati (4) and Parascaris sp. (1) were detected predominantly in muscles. Seroprevalence of T. canis was 14.2% and ELISA was thus more sensitive than PCR to detect infection with this parasite. Non-parametric multidimensional scaling and cluster analysis revealed that parasite communities could be grouped into an urban and a peri-urban cluster with high frequency of ascarid-positive rodents in urban and high frequency of F. glareoli in peri-urban sites. Prevalence rates of parasites in rodents with potential impact for human or veterinary public health are considerable and the monitoring of transmission cycles of carnivore parasites in intermediate rodent hosts is recommended to estimate the health

Small rodents as paratenic or intermediate hosts of carnivore parasites in Berlin, Germany.

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Jürgen Krücken

Full Text Available Rodents are important intermediate and paratenic hosts for carnivore parasites, including the important zoonotic agents Toxoplasma, Echinococcus and Toxocara. Monitoring of such parasites in rodents can be used to detect increasing risks for human and veterinary public health. Rodents were trapped at four sites in Berlin, two near the city center, two at the periphery. PCRs were conducted to detect Coccidia (target ITS-1 and specifically Toxoplasma gondii (repetitive element in brain and ascarids (ITS-2 in muscle or brain tissue. During necropsies, metacestodes were collected and identified using ITS-2 and 12S rRNA PCRs. An ELISA to detect antibodies against Toxocara canis ES antigens was performed. Within the 257 examined rodents, the most frequently observed parasite was Frenkelia glareoli predominantly found in Myodes glareolus. T. gondii was only detected in 12 rodents and Microtus spp. (although strongly underrepresented had a significantly increased chance of being positive. Neither Echinococcus nor typical Taenia parasites of dogs and cats were found but Mesocestoides litteratus and Taenia martis metacestodes were identified which can cause severe peritoneal or ocular cysticercosis in dogs, primates and humans. Using PCR, the ascarids T. canis (n = 8, Toxocara cati (4 and Parascaris sp. (1 were detected predominantly in muscles. Seroprevalence of T. canis was 14.2% and ELISA was thus more sensitive than PCR to detect infection with this parasite. Non-parametric multidimensional scaling and cluster analysis revealed that parasite communities could be grouped into an urban and a peri-urban cluster with high frequency of ascarid-positive rodents in urban and high frequency of F. glareoli in peri-urban sites. Prevalence rates of parasites in rodents with potential impact for human or veterinary public health are considerable and the monitoring of transmission cycles of carnivore parasites in intermediate rodent hosts is recommended to

Evaluation of optic nerve head blood flow in normal rats and a rodent model of non-arteritic ischemic optic neuropathy using laser speckle flowgraphy.

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Takako, Hidaka; Hideki, Chuman; Nobuhisa, Nao-I

2017-10-01

To evaluate optic nerve head (ONH) blood flow in normal rats and a rodent model of non-arteritic ischemic optic neuropathy (rNAION) in vivo using laser speckle flowgraphy (LSFG). Rats were under general anesthesia; to induce NAION, Rose Bengal (RB) was injected into the tail vein. After the administration of RB, the left ONH was photoactivated using an argon green laser. We measured ONH blood flow in the normal rats and the rNAION group (at 1, 3, 7, 14, and 28 days after the induction of NAION) using an LSFG-Micro. We used the mean blur rate (MBR) of the vessel region (MV) and MBR of the tissue region (MT) as indicators of blood flow. We compared the MBR of the right and left eyes in both the normal rats and the rNAION group. In the normal rats, there were no significant differences in MV or MT between the right and left eyes. In the rNAION group, the MV and MT of the affected eyes were significantly lower than those of the unaffected eyes at all time points. There were significant differences between the left/right MV and MT ratios seen before the induction of NAION and those observed at 1, 3, 7, 14, and 28 days after the induction of NAION. However, there were no significant differences in these parameters among any of post-NAION induction time points. Our results indicated that the ONH blood flow of the rNAION rats fell in the acute and chronic phases.

Prevalence and genetic diversity of Bartonella strains in rodents from northwestern Mexico.

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Rubio, André V; Ávila-Flores, Rafael; Osikowicz, Lynn M; Bai, Ying; Suzán, Gerardo; Kosoy, Michael Y

2014-12-01

Bartonella infections were investigated in wild rodents from northwestern Chihuahua, Mexico. A total of 489 rodents belonging to 14 species were surveyed in four areas. Bartonella bacteria were cultured from 50.1% of rodent samples (245/489). Infection rates ranged from 0% to 83.3% per rodent species, with no significant difference between sites except for Cynomys ludovicianus. Phylogenetic analyses of the citrate synthase gene (gltA) of the Bartonella isolates revealed 23 genetic variants (15 novel and 8 previously described), clustering into five phylogroups. Three phylogroups were associated with Bartonella vinsonii subsp. vinsonii, B. vinsonii subsp. arupensis, and B. washoensis, respectively. The other two phylogroups were not genetically related to any known Bartonella species. The genetic variants and phylogenetic groups exhibited a high degree of host specificity, mainly at the genus and family levels. This is the first study that describes the genetic diversity of Bartonella strains in wild rodents from Mexico. Considering that some variants found in this study are associated with Bartonella species that have been reported as zoonotic, more investigations are needed to further understand the ecology of Bartonella species in Mexican wildlife and their implications for human health.

The establishment of animal model of acute massive pulmonary embolism

International Nuclear Information System (INIS)

Lu Junliang; Yang Ning; Yang Jianping; Ma Junshan; Zhao Shijun

2008-01-01

Objective: To find a way of establishing the model of acute massive pulmonary embolism in dog. Methods: Seven dogs were selected with self-clots made outside the body transferring through a 10 F guiding catheter into the central branch of pulmonary artery via the femoral vein approach on one side and then under pressure monitor of pulmonary artery until the very branch of pulmonary artery was occluded. Blood gas and pulmonary arterial pressure were tested before and after the embolization, Pulmonary artery pressure was continuously monitored together with the examinations of angiography. The bilateral lung specimens were resected for histological examination 12 hours in average after the embolization for comparative study. Results: One animal died of cardiogenic shock after clots injection; the other one presented with tachycardia and premature ventricular beat causing partial recanalization 12 h later. The others were occluded successfully in central branch of pulmonary artery and the pulmonary arterial pressure reached above 50 mmHg after occlusion. Pathologic examination showed the formation of red and mix thrombi within the vascular lumens. Conclusions: This method for making acute massive pulmonary embolism animal model was reliable, feasible and reproducible, and could provide an animal model of acute massive pulmonary embolism for other correlative experiments. (authors)

Transcutaneous measurement of glomerular filtration rate in small rodents: through the skin for the win?

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Ellery, Stacey J; Cai, Xiaochu; Walker, David D; Dickinson, Hayley; Kett, Michelle M

2015-03-01

Rodent models of renal physiology and pathology are crucial to our understanding of the molecular, histological and functional sequelae that contribute to kidney diseases. One of the most important measures of renal function is glomerular filtration rate (GFR). While the accurate determination of GFR is pivotal to understanding the progression of disease and/or the benefits of treatment strategies, in rodents the conventional methods for assessment of GFR are inconvenient and cumbersome, not the least because they involve stress and often anaesthesia. The legitimacy of assay-based assessment of plasma and urine markers of GFR in mice has also been heavily scrutinized for their insensitivity to minor declines in GFR and inaccurate detection of renal biomarkers. While infusion-based clearance methods of GFR assessment are thus the gold standard in terms of accuracy, they are limited by the fact that they are primarily non-recovery procedures. This presents a dilemma when trying to document the progression of renal disease, as these measures cannot be taken in the same experimental subject. Here we review a technique of transcutaneous measurement of fluorescein isothiocyanate-labelled sinistrin to calculate GFR in small rodents, using a non-invasive clearance device (NIC-Kidney Device). This is a recently validated non-invasive technique for measuring GFR in small rodents that allows for the real-time measurement of GFR in conscious animals, without the need for plasma and urine assays. © 2014 Asian Pacific Society of Nephrology.

Phencyclidine-induced Loss of Asymmetric Spine Synapses in Rodent Prefrontal Cortex is Reversed by Acute and Chronic Treatment with Olanzapine

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Elsworth, John D; Morrow, Bret A; Hajszan, Tibor; Leranth, Csaba; Roth, Robert H

2011-01-01

Enduring cognitive deficits exist in schizophrenic patients, long-term abusers of phencyclidine (PCP), as well as in animal PCP models of schizophrenia. It has been suggested that cognitive performance and memory processes are coupled with remodeling of pyramidal dendritic spine synapses in prefrontal cortex (PFC), and that reduced spine density and number of spine synapses in the medial PFC of PCP-treated rats may potentially underlie, at least partially, the cognitive dysfunction previously observed in this animal model. The present data show that the decrease in number of asymmetric (excitatory) spine synapses in layer II/III of PFC, previously noted at 1-week post PCP treatment also occurs, to a lesser degree, in layer V. The decrease in the number of spine synapses in layer II/III was sustained and persisted for at least 4 weeks, paralleling the observed cognitive deficits. Both acute and chronic treatment with the atypical antipsychotic drug, olanzapine, starting at 1 week after PCP treatment at doses that restore cognitive function, reversed the asymmetric spine synapse loss in PFC of PCP-treated rats. Olanzapine had no significant effect on spine synapse number in saline-treated controls. These studies demonstrate that the effect of PCP on asymmetric spine synapse number in PFC lasts at least 4 weeks in this model. This spine synapse loss in PFC is reversed by acute treatment with olanzapine, and this reversal is maintained by chronic oral treatment, paralleling the time course of the restoration of the dopamine deficit, and normalization of cognitive function produced by olanzapine. PMID:21677652

Synanthropic rodents as possible reservoirs of shigatoxigenic Escherichia coli strains

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Ximena eBlanco Crivelli

2012-11-01

Full Text Available Shigatoxigenic Escherichia coli (STEC strains are worldwide zoonotic pathogen responsible for different cases of human disease including hemolytic uremic syndrome (HUS. Transmission of STEC to humans occurs through the consumption of food and water contaminated by faeces of carriers and by person-to-person contact.The objective of this study was twofold: (a to investigate whether synanthropic rodents are possible reservoirs of STEC in the urban area and (b whether a particular genus out of synanthropic rodent is the principal carrier of STEC.One hundred forty-five rodents were captured in Buenos Aires City. Screening for stx1/stx2 and rfbO157 was done by PCR from the confluence zone. STEC isolates were further characterized with biochemical tests by standard methods. Additional virulence factors (eae, ehxA and saa were also determined by PCR. Forty-one of the rodents were necropsied and sample of kidney and small and large intestine were taken for histopathological diagnosis. The samples sections were stained with hematoxylin-eosin, and observed by light microscopy to evaluate the systemic involvement of these species in natural infections. STEC was isolated from seven out of twenty seven suspect animals at screening. The following genotypes were found in the STEC strains: stx1/stx2/ehxA (1, stx2 (4, stx2/ehxA (1, stx2/ehxA/eae (1. Neither gross nor microscopic lesions compatible with those produced by Shiga toxin were observed in the studied organs of necropsied rodents.The bivariate analysis including the hundred forty-five rodents data showed that the isolation of STEC is associated positively to Rattus genus. This synanthropic species may play a role in the transmissibility of the agent thus being a risk to the susceptible population. Their control should be included specifically in actions to dismiss the contamination of food and water by STEC in the urban area, as additional strategies for epidemiological control.

Microvascular anastomosis in rodent model evaluated by Fourier domain Doppler optical coherence tomography

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Huang, Yong; Tong, Dedi; Zhu, Shan; Wu, Lehao; Ibrahim, Zuhaib; Lee, WP Andrew; Brandacher, Gerald; Kang, Jin U.

2014-03-01

Vascular and microvascular anastomosis are critical components of reconstructive microsurgery, vascular surgery and transplant surgery. Imaging modality that provides immediate, real-time in-depth view and 3D structure and flow information of the surgical site can be a great valuable tool for the surgeon to evaluate surgical outcome following both conventional and innovative anastomosis techniques, thus potentially increase the surgical success rate. Microvascular anastomosis for vessels with outer diameter smaller than 1.0 mm is extremely challenging and effective evaluation of the outcome is very difficult if not impossible using computed tomography (CT) angiograms, magnetic resonance (MR) angiograms and ultrasound Doppler. Optical coherence tomography (OCT) is a non-invasive high-resolution (micron level), high-speed, 3D imaging modality that has been adopted widely in biomedical and clinical applications. Phaseresolved Doppler OCT that explores the phase information of OCT signals has been shown to be capable of characterizing dynamic blood flow clinically. In this work, we explore the capability of Fourier domain Doppler OCT as an evaluation tool to detect commonly encountered post-operative complications that will cause surgical failure and to confirm positive result with surgeon's observation. Both suture and cuff based techniques were evaluated on the femoral artery and vein in the rodent model.

BEHAVIOURAL STUDIES ON SOME RHODESIAN RODENTS

African Journals Online (AJOL)

behaviour, . courtship, parental and juvenile behaviour and activity patterns. ... behavioural observations were facilitated by the development of a glass-fronted ~'double-storey" cage which ..... Adolescent siblings in both single sex and mixed groups ..... Wild rodents as Laboratory Animals and their contribution to medical.

A test of five mechanisms of species coexistence between rodents in ...

African Journals Online (AJOL)

A test of five mechanisms of species coexistence between rodents in a southern African savanna. M.R. Perrin, B.P. Kotler. Abstract. The operation of five different mechanisms of species coexistence in a community of rodents was examined in a semi-arid Kalahari savanna in southern Africa. The two most common species ...

The G protein-coupled receptor subset of the dog genome is more similar to that in humans than rodents.

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Haitina, Tatjana; Fredriksson, Robert; Foord, Steven M; Schiöth, Helgi B; Gloriam, David E

2009-01-15

The dog is an important model organism and it is considered to be closer to humans than rodents regarding metabolism and responses to drugs. The close relationship between humans and dogs over many centuries has lead to the diversity of the canine species, important genetic discoveries and an appreciation of the effects of old age in another species. The superfamily of G protein-coupled receptors (GPCRs) is one of the largest gene families in most mammals and the most exploited in terms of drug discovery. An accurate comparison of the GPCR repertoires in dog and human is valuable for the prediction of functional similarities and differences between the species. We searched the dog genome for non-olfactory GPCRs and obtained 353 full-length GPCR gene sequences, 18 incomplete sequences and 13 pseudogenes. We established relationships between human, dog, rat and mouse GPCRs resolving orthologous pairs and species-specific duplicates. We found that 12 dog GPCR genes are missing in humans while 24 human GPCR genes are not part of the dog GPCR repertoire. There is a higher number of orthologous pairs between dog and human that are conserved as compared with either mouse or rat. In almost all cases the differences observed between the dog and human genomes coincide with other variations in the rodent species. Several GPCR gene expansions characteristic for rodents are not found in dog. The repertoire of dog non-olfactory GPCRs is more similar to the repertoire in humans as compared with the one in rodents. The comparison of the dog, human and rodent repertoires revealed several examples of species-specific gene duplications and deletions. This information is useful in the selection of model organisms for pharmacological experiments.

The G protein-coupled receptor subset of the dog genome is more similar to that in humans than rodents

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Schiöth Helgi B

2009-01-01

Full Text Available Abstract Background The dog is an important model organism and it is considered to be closer to humans than rodents regarding metabolism and responses to drugs. The close relationship between humans and dogs over many centuries has lead to the diversity of the canine species, important genetic discoveries and an appreciation of the effects of old age in another species. The superfamily of G protein-coupled receptors (GPCRs is one of the largest gene families in most mammals and the most exploited in terms of drug discovery. An accurate comparison of the GPCR repertoires in dog and human is valuable for the prediction of functional similarities and differences between the species. Results We searched the dog genome for non-olfactory GPCRs and obtained 353 full-length GPCR gene sequences, 18 incomplete sequences and 13 pseudogenes. We established relationships between human, dog, rat and mouse GPCRs resolving orthologous pairs and species-specific duplicates. We found that 12 dog GPCR genes are missing in humans while 24 human GPCR genes are not part of the dog GPCR repertoire. There is a higher number of orthologous pairs between dog and human that are conserved as compared with either mouse or rat. In almost all cases the differences observed between the dog and human genomes coincide with other variations in the rodent species. Several GPCR gene expansions characteristic for rodents are not found in dog. Conclusion The repertoire of dog non-olfactory GPCRs is more similar to the repertoire in humans as compared with the one in rodents. The comparison of the dog, human and rodent repertoires revealed several examples of species-specific gene duplications and deletions. This information is useful in the selection of model organisms for pharmacological experiments.

Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil's Amazon Rainforest.

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Guimarães Marques, Marcia J; Reyes-Garcia, Selvin Z; Marques-Carneiro, José E; Lopes-Silva, Leonardo B; Andersen, Monica L; Cavalheiro, Esper A; Scorza, Fulvio A; Scorza, Carla A

2018-01-01

Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed

Having your cake and eating it too: A habit of comfort food may link chronic social stress exposure and acute stress-induced cortisol hyporesponsiveness.

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Stress has been tied to changes in eating behavior and food choice. Previous studies in rodents have shown that chronic stress increases palatable food intake which, in turn, increases mesenteric fat and inhibits acute stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity. The effect of...

New activity-based funding model for Australian private sector overnight rehabilitation cases: the rehabilitation Australian National Sub-Acute and Non-Acute Patient (AN-SNAP) model.

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Hanning, Brian; Predl, Nicolle

2015-09-01

Traditional overnight rehabilitation payment models in the private sector are not based on a rigorous classification system and vary greatly between contracts with no consideration of patient complexity. The payment rates are not based on relative cost and the length-of-stay (LOS) point at which a reduced rate applies (step downs) varies markedly. The rehabilitation Australian National Sub-Acute and Non-Acute Patient (AN-SNAP) model (RAM), which has been in place for over 2 years in some private hospitals, bases payment on a rigorous classification system, relative cost and industry LOS. RAM is in the process of being rolled out more widely. This paper compares and contrasts RAM with traditional overnight rehabilitation payment models. It considers the advantages of RAM for hospitals and Australian Health Service Alliance. It also considers payment model changes in the context of maintaining industry consistency with Electronic Claims Lodgement and Information Processing System Environment (ECLIPSE) and health reform generally.

An in-vitro-in-vivo model for the transdermal delivery of cholecalciferol for the purposes of rodent management.

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Davies, J; Ingham, A

2015-06-20

The natural selection of anticoagulant resistant rats has resulted in a need for an alternative to anticoagulant rodenticides which differs in both active ingredient and in the method of dosing. Cholecalciferol toxicity to rodents using the dermal route is demonstrated using a variety of penetration enhancing formulations in two in-vitro models and finally in-vivo. A 1 ml dose of 50/50 (v/v) DMSO/ethanol containing 15% (v/v) PEG 200 and 20% (w/v) cholecalciferol was judged as 'sufficiently effective' in line with the European Union's Biocidal Products Regulation (No. 528/2012) during in-vivo studies. This dose was found to cause 100% mortality in a rat population in 64.4h (± 22h). Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

An experimental model of hemolysis-induced acute pancreatitis

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Saruc M.

2003-01-01

Full Text Available The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH in 20% (v/v ethanol on the first experimental day (day 0. One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha and platelet-activating factor (PAF contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70% of 50 rats, moderate hemolysis in seven (14%, and no hemolysis in eight (16%. Thirty-three of 35 (94.2% rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8% had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.

Timing matters: the interval between acute stressors within chronic mild stress modifies behavioral and physiologic stress responses in male rats.

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Cavigelli, Sonia A; Bao, Alexander D; Bourne, Rebecca A; Caruso, Michael J; Caulfield, Jasmine I; Chen, Mary; Smyth, Joshua M

2018-04-12

Chronic mild stress can lead to negative health outcomes. Frequency, duration, and intensity of acute stressors can affect health-related processes. We tested whether the temporal pattern of daily acute stressors (clustered or dispersed across the day) affects depression-related physiology. We used a rodent model to keep stressor frequency, duration, and intensity constant, and experimentally manipulated the temporal pattern of acute stressors delivered during the active phase of the day. Adult male Sprague-Dawley rats were exposed to one of three chronic mild stress groups: Clustered: stressors that occurred within 1 hour of each other (n = 21), Dispersed: stressors that were spread out across the active phase (n = 21), and Control: no stressors presented (n = 21). Acute mild stressors included noise, strobe lights, novel cage, cage tilt, wet bedding, and water immersion. Depression-related outcomes included: sucrose preference, body weight, circulating glucocorticoid (corticosterone) concentration after a novel acute stressor and during basal morning and evening times, and endotoxin-induced circulating interleukin-6 concentrations. Compared to control rats, those in the Clustered group gained less weight, consumed less sucrose, had a blunted acute corticosterone response, and an accentuated acute interleukin-6 response. Rats in the Dispersed group had an attenuated corticosterone decline during the active period and after an acute stressor compared to the Control group. During a chronic mild stress experience, the temporal distribution of daily acute stressors affected health-related physiologic processes. Regular exposure to daily stressors in rapid succession may predict more depression-related symptoms, whereas exposure to stressors dispersed throughout the day may predict diminished glucocorticoid negative feedback.

Establishment of selected acute pulmonary thromboembolism model in experimental sheep

International Nuclear Information System (INIS)

Fan Jihai; Gu Xiulian; Chao Shengwu; Zhang Peng; Fan Ruilin; Wang Li'na; Wang Lulu; Wang Ling; Li Bo; Chen Taotao

2010-01-01

Objective: To establish a selected acute pulmonary thromboembolism model in experimental sheep suitable for animal experiment. Methods: By using Seldinger's technique the catheter sheath was placed in both the femoral vein and femoral artery in ten sheep. Under C-arm DSA guidance the catheter was inserted through the catheter sheath into the pulmonary artery. Via the catheter appropriate amount of sheep autologous blood clots was injected into the selected pulmonary arteries. The selected acute pulmonary thromboembolism model was thus established. Pulmonary angiography was performed to check the results. The pulmonary arterial pressure, femoral artery pressure,heart rates and partial pressure of oxygen in arterial blood (PaO 2 ) were determined both before and after the treatment. The above parameters obtained after the procedure were compared with the recorded parameters measured before the procedure, and the sheep model quality was evaluated. Results: The baseline of pulmonary arterial pressure was (27.30 ± 9.58) mmHg,femoral artery pressure was (126.4 ± 13.72) mmHg, heart rate was (103 ± 15) bpm and PaO 2 was (87.7 ± 12.04) mmHg. Sixty minutes after the injection of (30 ± 5) ml thrombotic agglomerates, the pulmonary arterial pressures rose to (52 ± 49) mmHg, femoral artery pressures dropped to (100 ± 21) mmHg. The heart rates went up to (150 ± 26) bpm. The PaO 2 fell to (25.3 ± 11.2) mmHg. After the procedure the above parameters were significantly different from that measured before the procedure in all ten animals (P < 0.01). The pulmonary arteriography clearly demonstrated that the selected pulmonary arteries were successfully embolized. Conclusion: The anatomy of sheep's femoral veins,vena cava system, pulmonary artery and right heart system are suitable for the establishment of the catheter passage, for this reason, selected acute pulmonary thromboembolism model can be easily created in experimental sheep. The technique is feasible and the model

Correlates of Recent Declines of Rodents in Northern and Southern Australia: Habitat Structure Is Critical.

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Michael J Lawes

Full Text Available Australia has experienced dramatic declines and extinctions of its native rodent species over the last 200 years, particularly in southern Australia. In the tropical savanna of northern Australia significant declines have occurred only in recent decades. The later onset of these declines suggests that the causes may differ from earlier declines in the south. We examine potential regional effects (northern versus southern Australia on biological and ecological correlates of range decline in Australian rodents. We demonstrate that rodent declines have been greater in the south than in the tropical north, are strongly influenced by phylogeny, and are consistently greater for species inhabiting relatively open or sparsely vegetated habitat. Unlike in marsupials, where some species have much larger body size than rodents, body mass was not an important predictor of decline in rodents. All Australian rodent species are within the prey-size range of cats (throughout the continent and red foxes (in the south. Contrary to the hypothesis that mammal declines are related directly to ecosystem productivity (annual rainfall, our results are consistent with the hypothesis that disturbances such as fire and grazing, which occur in non-rainforest habitats and remove cover used by rodents for shelter, nesting and foraging, increase predation risk. We agree with calls to introduce conservation management that limits the size and intensity of fires, increases fire patchiness and reduces grazing impacts at ecological scales appropriate for rodents. Controlling feral predators, even creating predator-free reserves in relatively sparsely-vegetated habitats, is urgently required to ensure the survival of rodent species, particularly in northern Australia where declines are not yet as severe as those in the south.

Nonhuman Primate Models of Chikungunya Virus Infection and Disease (CHIKV NHP Model

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Rebecca Broeckel

2015-09-01

Full Text Available Chikungunya virus (CHIKV is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and the Indian Ocean region established CHIKV as a global health concern. This concern was further solidified by the recent incursion of the virus into the Western hemisphere, a region without pre-existing immunity. Nonhuman primates (NHPs serve as excellent animal models for understanding CHIKV pathogenesis and pre-clinical assessment of vaccines and therapeutics. NHPs present advantages over rodent models because they are a natural amplification host for CHIKV and they share significant genetic and physiological homology with humans. CHIKV infection in NHPs results in acute fever, rash, viremia and production of type I interferon. NHPs develop CHIKV-specific B and T-cells, generating neutralizing antibodies and CHIKV-specific CD4+ and CD8+ T-cells. CHIKV establishes a persistent infection in NHPs, particularly in cynomolgus macaques, because infectious virus could be recovered from spleen, liver, and muscle as late as 44 days post infection. NHPs are valuable models that are useful in preclinical testing of vaccines and therapeutics and uncovering the details of CHIKV pathogenesis.

Intestinal Helminths in Different Species of Rodents in North Khorasan Province, Northeast of Iran

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Kourosh ARZAMANI

2017-06-01

Full Text Available Background: Rodents are an important source of zoonotic diseases for human. The aim of this study was to determine the infectivity of rodents with intestinal helminths in North Khorasan Province, Iran.Methods: One hundred and thirteen rodents were collected using different collection methods such as kill and live traps, digging of their burrow, filling of their hiding places with water and hand net during 2011-2013. Their alimentary canals were removed in the laboratory and helminths were determined in the department of parasitology, Tehran University of Medical Sciences.Results: Thirteen species of helminths parasites were found in 13 species of rodents, including Aspiculuris tetraptera, Hymenolepis diminuta, Nippostrongylus brasiliensis, Protospirura Seurat, Rictolaria ratti, Skrjabinitaenia lobata, Streptopharagus kuntzi, Syphacia obvelata, Taenia taeniaeformis, Trichuris muris, Cysticercus fasciolaris, Acanthocephal. spp and Trichuris spp. Some of them were reported for the first time in new host in Iran. S. obvelata and A. tetraptera were the most frequent parasites and P. Seurat, R. ratti and C. fasciolaris were found only in one rodent.Conclusion: This is the first study to investigate the intestinal parasites in rodents in this area. Among different species identified, some of helminths were reported in new host.

Intestinal Helminths in Different Species of Rodents in North Khorasan Province, Northeast of Iran.

Science.gov (United States)

Arzamani, Kourosh; Salehi, Mitra; Mobedi, Iraj; Adinezade, Amir; Hasanpour, Hamid; Alavinia, Mohammad; Darvish, Jamshid; Shirzadi, Mohammad Reza; Mohammadi, Zeinolabedin

2017-01-01

Rodents are an important source of zoonotic diseases for human. The aim of this study was to determine the infectivity of rodents with intestinal helminths in North Khorasan Province, Iran. One hundred and thirteen rodents were collected using different collection methods such as kill and live traps, digging of their burrow, filling of their hiding places with water and hand net during 2011-2013. Their alimentary canals were removed in the laboratory and helminths were determined in the department of parasitology, Tehran University of Medical Sciences. Thirteen species of helminths parasites were found in 13 species of rodents, including Aspiculuris tetraptera, Hymenolepis diminuta, Nippostrongylus brasiliensis, Protospirura Seurat, Rictolaria ratti, Skrjabinitaenia lobata, Streptopharagus kuntzi, Syphacia obvelata, Taenia taeniaeformis, Trichuris muris, Cysticercus fasciolaris, Acanthocephal. spp and Trichuris spp . Some of them were reported for the first time in new host in Iran. S. obvelata and A. tetraptera were the most frequent parasites and P. Seurat, R. ratti and C. fasciolaris were found only in one rodent. This is the first study to investigate the intestinal parasites in rodents in this area. Among different species identified, some of helminths were reported in new host.

A Geographic Information Systems (GIS)-based analysis of modern South African rodent distributions, habitat use, and environmental tolerances.

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Campbell, Timothy L; Lewis, Patrick J; Thies, Monte L; Williams, Justin K

2012-11-01

GOALS OF THIS STUDY WERE TO: (1) develop distributional maps of modern rodent genera throughout the countries of South Africa, Lesotho, and Swaziland by georeferencing museum specimens; (2) assess habitat preferences for genera by cross-referencing locality position with South African vegetation; and (3) identify mean annual precipitation and temperature range where the genera are located. Conterminous South Africa including the countries of Lesotho and Swaziland Digital databases of rodent museum specimens housed in the Ditsong National Museum of Natural History, South Africa (DM), and the Division of Mammals, National Museum of Natural History, Smithsonian Institution, United States (NMNH), were acquired and then sorted into a subset of specimens with associated coordinate data. The coordinate data were then used to develop distributional maps for the rodent genera present within the study area. Percent habitat occupation and descriptive statistics for six climatic variables were then determined for each genus by cross-referencing locality positions with vegetation and climatic maps. This report presents a series of maps illustrating the distribution of 35 rodent genera based on 19,471 geo-referenced specimens obtained from two major collections. Inferred habitat use by taxon is provided for both locality and specimen percent occurrence at three hierarchical habitat levels: biome, bioregion, and vegetation unit. Descriptive statistics for six climatic variables are also provided for each genus based on locality and specimen percent incidence. As rodent faunas are commonly used in paleoenvironmental reconstructions, an accurate assessment of rodent environmental tolerance ranges is necessary before confidence can be placed in an actualistic model. While the data presented here represent only a subset of the modern geographic distributions for many of the taxa examined, a wide range of environmental regimes are observed, suggesting that more research is necessary

A Geographic Information Systems (GIS)-based analysis of modern South African rodent distributions, habitat use, and environmental tolerances

Science.gov (United States)

Campbell, Timothy L; Lewis, Patrick J; Thies, Monte L; Williams, Justin K

2012-01-01

Goals of this study were to: (1) develop distributional maps of modern rodent genera throughout the countries of South Africa, Lesotho, and Swaziland by georeferencing museum specimens; (2) assess habitat preferences for genera by cross-referencing locality position with South African vegetation; and (3) identify mean annual precipitation and temperature range where the genera are located. Conterminous South Africa including the countries of Lesotho and Swaziland Digital databases of rodent museum specimens housed in the Ditsong National Museum of Natural History, South Africa (DM), and the Division of Mammals, National Museum of Natural History, Smithsonian Institution, United States (NMNH), were acquired and then sorted into a subset of specimens with associated coordinate data. The coordinate data were then used to develop distributional maps for the rodent genera present within the study area. Percent habitat occupation and descriptive statistics for six climatic variables were then determined for each genus by cross-referencing locality positions with vegetation and climatic maps. This report presents a series of maps illustrating the distribution of 35 rodent genera based on 19,471 geo-referenced specimens obtained from two major collections. Inferred habitat use by taxon is provided for both locality and specimen percent occurrence at three hierarchical habitat levels: biome, bioregion, and vegetation unit. Descriptive statistics for six climatic variables are also provided for each genus based on locality and specimen percent incidence. As rodent faunas are commonly used in paleoenvironmental reconstructions, an accurate assessment of rodent environmental tolerance ranges is necessary before confidence can be placed in an actualistic model. While the data presented here represent only a subset of the modern geographic distributions for many of the taxa examined, a wide range of environmental regimes are observed, suggesting that more research is necessary

Surfaces and spaces: troubleshooting the study of dietary niche space overlap between North American stem primates and rodents

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Prufrock, Kristen A.; López-Torres, Sergi; Silcox, Mary T.; Boyer, Doug M.

2016-06-01

Dental topographic metrics provide quantitative, biologically meaningful data on the three-dimensional (3D) form of teeth. In this study, three dental topographic metrics (Dirichlet normal energy (DNE), relief index (RFI), and orientation patch count rotated (OPCR)) are used to evaluate the presence of dietary niche overlap between North American plesiadapoid primates (Plesiadapidae, Carpolestidae, and Saxonellidae) and early rodents. Calculation of these metrics requires researchers to modify the 3D surface models of the teeth by cropping them to a region of interest and/or orienting them. The current study therefore also examines the error introduced by cropping and orientation, and evaluates the contribution of these metrics to the niche overlap hypothesis. Our results indicate that cropping creates significantly more variation in RFI than DNE. Furthermore, orientation is an even larger source of variation in the calculation of RFI than cropping. Orientation does not strongly influence OPCR values. However, none of these sources of error are significant enough to undermine the extent to which these metrics can speak to the niche overlap hypothesis. The DNE and RFI results suggest that carpolestids and saxonellids had very different molar morphologies from early rodents, and thus these groups were not adapted to consume the same resources. Some plesiadapids show similar levels of occlusal curvature, relief, and complexity to early rodents. The plesiadapid Chiromyoides, which has distinctively low cusps and weak shearing crest development, has molars that are the most rodent-like of all taxa compared. This suggests that Chiromyoides had a dietary niche that overlapped with early rodents and would have been the most likely to be competing over food resources. Results from the plesiadapoid-rodent dental topographic analysis highlight the utility of DNE for detecting more fine-scaled differences in occlusal surface morphology than OPCR, whereas RFI provided valuable

Brain Stimulation Reward Supports More Consistent and Accurate Rodent Decision-Making than Food Reward.

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McMurray, Matthew S; Conway, Sineadh M; Roitman, Jamie D

2017-01-01

Animal models of decision-making rely on an animal's motivation to decide and its ability to detect differences among various alternatives. Food reinforcement, although commonly used, is associated with problematic confounds, especially satiety. Here, we examined the use of brain stimulation reward (BSR) as an alternative reinforcer in rodent models of decision-making and compared it with the effectiveness of sugar pellets. The discriminability of various BSR frequencies was compared to differing numbers of sugar pellets in separate free-choice tasks. We found that BSR was more discriminable and motivated greater task engagement and more consistent preference for the larger reward. We then investigated whether rats prefer BSR of varying frequencies over sugar pellets. We found that animals showed either a clear preference for sugar reward or no preference between reward modalities, depending on the frequency of the BSR alternative and the size of the sugar reward. Overall, these results suggest that BSR is an effective reinforcer in rodent decision-making tasks, removing food-related confounds and resulting in more accurate, consistent, and reliable metrics of choice.

Anatomy and Histology of Rodent and Human Major Salivary Glands

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Amano, Osamu; Mizobe, Kenichi; Bando, Yasuhiko; Sakiyama, Koji

2012-01-01

Major salivary glands of both humans and rodents consist of three pairs of macroscopic glands: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638–1686), Thomas Wharton (1614–1673), and Caspar Bartholin (1655–1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands. The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands. PMID:23209333

Occurrence of ectoparasitic arthropods associated with rodents in Hail region northern Saudi Arabia.

Science.gov (United States)

Asiry, Khalid A; Fetoh, Badr El-Sabah A

2014-09-01

Ectoparasitic arthropods are a diverse element of the Saudi fauna. Due to this, a survey of ectoparasites associated with rodents was conducted as a preliminary study in five districts of Hail region of northern Saudi Arabia for the first time. Ectoparasites extracted from 750 rodents were sampled and identified by recording their frequency of appearance. Results revealed that 1,287 ectoparasites infested 316 of the captured rodent hosts. These ectoparasites parasitized on four species of rodents including three species of rats Rattus rattus rattus, Rattus rattus frugivorus, and Rattus rattus alexandrinus and one species of mouse Acomys dimidiatus (Rodentia: Muridae). The ectoparasites belong to four different groups: ticks, fleas, lice, and mites. Ticks were the highest in the number, while fleas were the lowest among all the extracted ectoparasite groups. The collected ectoparasitic arthropods consisted of seven species. Ticks were of two species: Rhipicephalus turanicus and Rhipicephalus sanguineus (Acari: Ixodidae), fleas were of two species: Xenopsylla cheopis and Xenopsyllus conformis mycerini (Siphonaptera: Pulicidae), lice was a single species: Polyplax serrata (Anoplura: Hoplopleuridae), and mites were of two species: Laelaps nuttali and Laelaps echidninus (Mesostigmata: Laelapidae). The findings of the study showed that the intensity of infestation was varied between rodent host sexes, wherein females had the highest rate of parasitic infestation, and the parasitic index of appearance was very high for one group of parasites (i.e., ticks). The parasitic prevalence was 42.13 % on rodents, and mites were the most prevalent parasite species. Overall, this study was carried out to establish baseline data for ectoparasite-infested rodents in Hail region, Saudi Arabia, and may help for appropriate planning to control zoonotic diseases in this area.

Effects of Arachidonic Acid Supplementation on Acute Anabolic Signaling and Chronic Functional Performance and Body Composition Adaptations.

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Eduardo O De Souza

Full Text Available The primary purpose of this investigation was to examine the effects of arachidonic acid (ARA supplementation on functional performance and body composition in trained males. In addition, we performed a secondary study looking at molecular responses of ARA supplementation following an acute exercise bout in rodents.Thirty strength-trained males (age: 20.4 ± 2.1 yrs were randomly divided into two groups: ARA or placebo (i.e. CTL. Then, both groups underwent an 8-week, 3-day per week, non-periodized training protocol. Quadriceps muscle thickness, whole-body composition scan (DEXA, muscle strength, and power were assessed at baseline and post-test. In the rodent model, male Wistar rats (~250 g, ~8 weeks old were pre-fed with either ARA or water (CTL for 8 days and were fed the final dose of ARA prior to being acutely strength trained via electrical stimulation on unilateral plantar flexions. A mixed muscle sample was removed from the exercised and non-exercised leg 3 hours post-exercise.Lean body mass (2.9%, p<0.0005, upper-body strength (8.7%, p<0.0001, and peak power (12.7%, p<0.0001 increased only in the ARA group. For the animal trial, GSK-β (Ser9 phosphorylation (p<0.001 independent of exercise and AMPK phosphorylation after exercise (p-AMPK less in ARA, p = 0.041 were different in ARA-fed versus CTL rats.Our findings suggest that ARA supplementation can positively augment strength-training induced adaptations in resistance-trained males. However, chronic studies at the molecular level are required to further elucidate how ARA combined with strength training affect muscle adaptation.

A modified beam-walking apparatus for assessment of anxiety in a rodent model of blast traumatic brain injury.

Science.gov (United States)

Sweis, Brian M; Bachour, Salam P; Brekke, Julia A; Gewirtz, Jonathan C; Sadeghi-Bazargani, Homayoun; Hevesi, Mario; Divani, Afshin A

2016-01-01

The elevated plus maze (EPM) is used to assess anxiety in rodents. Beam-walking tasks are used to assess vestibulomotor function. Brain injury in rodents can disrupt performance on both of these tasks. Developing novel paradigms that integrate tasks like these can reduce the need for multiple tests when attempting to assess multiple behaviors in the same animal. Using adult male rats, we evaluated the use of a modified beam-walking (MBW) apparatus as a surrogate indicator for anxiety. We used a model of blast-induced traumatic brain injury (bTBI). A total of 39 rats were assessed before and at 3, 6, 24, 72, and 168h either post- bTBI (n=33) or no-injury (n=6) using both EPM and MBW. A novel anxiety index was calculated that encompassed peeks and re-emergences on MBW. The proposed MBW anxiety index was compared with the standard anxiety index calculated from exploration into different sections of EPM. Post- bTBI, rats had an increased anxiety index when measured using EPM. Similarly, they peeked or fully emerged less out of the safe box on MBW. It was found that this novel MBW anxiety index captured similar aspects of behavior when compared to the standard anxiety index obtained from EPM. Further, these effects were dissociated from the effects of bTBI on motor function simultaneously measured on MBW. Over the course of 168h post-bTBI, rats gradually recovered on both EPM and MBW. The MBW apparatus succeeded at capturing and dissociating two separate facets of rat behavior, motor function and anxiety, simultaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

Transformation of the rodent malaria parasite Plasmodium chabaudi and generation of a stable fluorescent line PcGFPCON

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Reece Sarah E

2008-09-01

Full Text Available Abstract Background The rodent malaria parasite Plasmodium chabaudi has proven of great value in the analysis of fundamental aspects of host-parasite-vector interactions implicated in disease pathology and parasite evolutionary ecology. However, the lack of gene modification technologies for this model has precluded more direct functional studies. Methods The development of in vitro culture methods to yield P. chabaudi schizonts for transfection and conditions for genetic modification of this rodent malaria model are reported. Results Independent P. chabaudi gene-integrant lines that constitutively express high levels of green fluorescent protein throughout their life cycle have been generated. Conclusion Genetic modification of P. chabaudi is now possible. The production of genetically distinct reference lines offers substantial advances to our understanding of malaria parasite biology, especially interactions with the immune system during chronic infection.

Utilization and cost of a new model of care for managing acute knee injuries: the Calgary acute knee injury clinic

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Lau Breda HF

2012-12-01

Full Text Available Abstract Background Musculoskeletal disorders (MSDs affect a large proportion of the Canadian population and present a huge problem that continues to strain primary healthcare resources. Currently, the Canadian healthcare system depicts a clinical care pathway for MSDs that is inefficient and ineffective. Therefore, a new inter-disciplinary team-based model of care for managing acute knee injuries was developed in Calgary, Alberta, Canada: the Calgary Acute Knee Injury Clinic (C-AKIC. The goal of this paper is to evaluate and report on the appropriateness, efficiency, and effectiveness of the C-AKIC through healthcare utilization and costs associated with acute knee injuries. Methods This quasi-experimental study measured and evaluated cost and utilization associated with specific healthcare services for patients presenting with acute knee injuries. The goal was to compare patients receiving care from two clinical care pathways: the existing pathway (i.e. comparison group and a new model, the C-AKIC (i.e. experimental group. This was accomplished through the use of a Healthcare Access and Patient Satisfaction Questionnaire (HAPSQ. Results Data from 138 questionnaires were analyzed in the experimental group and 136 in the comparison group. A post-hoc analysis determined that both groups were statistically similar in socio-demographic characteristics. With respect to utilization, patients receiving care through the C-AKIC used significantly less resources. Overall, patients receiving care through the C-AKIC incurred 37% of the cost of patients with knee injuries in the comparison group and significantly incurred less costs when compared to the comparison group. The total aggregate average cost for the C-AKIC group was $2,549.59 compared to $6,954.33 for the comparison group (p Conclusions The Calgary Acute Knee Injury Clinic was able to manage and treat knee injured patients for less cost than the existing state of healthcare delivery. The

Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model

Energy Technology Data Exchange (ETDEWEB)

Stefano, J.T.; Pereira, I.V.A.; Torres, M.M.; Bida, P.M. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Coelho, A.M.M. [Disciplina de Transplante de Órgãos do Aparelho Digestivo (LIM-37), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Xerfan, M.P. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Cogliati, B. [Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); Barbeiro, D.F. [Disciplina de Emergências Clínicas (LIM-51), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mazo, D.F.C. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Kubrusly, M.S.; D' Albuquerque, L.A.C. [Disciplina de Transplante de Órgãos do Aparelho Digestivo (LIM-37), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Souza, H.P. [Disciplina de Emergências Clínicas (LIM-51), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carrilho, F.J.; Oliveira, C.P. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

2015-02-24

Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg{sup -1}·day{sup -1} by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.

Homeobox Genes in the Rodent Pineal Gland

DEFF Research Database (Denmark)

Rath, Martin Fredensborg; Rohde, Kristian; Klein, David C

2013-01-01

The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential...... for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental...... functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function...

Analysis of acute myocardial infarction occurance in Saratov region using GIS-technologies and prognostic modeling

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SokolovI.M.

2012-09-01

Full Text Available

The research objective: To find estimation tools of incidence of acute myocardial infarction at the regional level and to optimize organization of medical assistance to patients with acute coronary pathology. Materials. With the use of statistics of territorial distribution of acute myocardial infarction incidence in the region and GIS-TECHNOLOGIES the statistical analysis and mathematical modelling of the spatially-organizational data has been carried out. Results. On the basis of the received results the prognostic model of development of acute coronary pathology has been generated. Measures on optimization of organization of medical assistance to patients with an acute coronary pathology have been stated. Conclusion. Methods of intellectual support of the doctor may become effective in formation of organizational structure of the system of stage-by-stage qualified and specialized aid to patients with acute coronary syndrome.

In vivo imaging of neuroinflammation in the rodent brain with [{sup 11}C]SSR180575, a novel indoleacetamide radioligand of the translocator protein (18 kDa)

Energy Technology Data Exchange (ETDEWEB)

Chauveau, Fabien [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Universite Paris Sud, INSERM U1023, Orsay (France); Universite Lyon 1, Creatis, CNRS UMR 5220, INSERM U630, INSA Lyon, Lyon (France); Boutin, Herve [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Universite Paris Sud, INSERM U1023, Orsay (France); University of Manchester, Faculty of Life Sciences, Manchester (United Kingdom); Camp, Nadja van; Tavitian, Bertrand [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Universite Paris Sud, INSERM U1023, Orsay (France); Thominiaux, Cyrille; Dolle, Frederic [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Hantraye, Philippe [CEA, DSV, IBM, MIRCEN, Fontenay-aux-Roses (France); Rivron, Luc [Sanofi-Aventis, GMPK-Global Isotope Chemistry and Metabolite Synthesis Department (ICMS), Paris (France); Marguet, Frank; Castel, Marie-Noelle; Rooney, Thomas; Benavides, Jesus [Sanofi-Aventis, CNS Department, Paris (France)

2011-03-15

Neuroinflammation is involved in neurological disorders through the activation of microglial cells. Imaging of neuroinflammation with radioligands for the translocator protein (18 kDa) (TSPO) could prove to be an attractive biomarker for disease diagnosis and therapeutic evaluation. The indoleacetamide-derived 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, SSR180575, is a selective high-affinity TSPO ligand in human and rodents with neuroprotective effects. Here we report the radiolabelling of SSR180575 with {sup 11}C and in vitro and in vivo imaging in an acute model of neuroinflammation in rats. The image contrast and the binding of [{sup 11}C]SSR180575 are higher than that obtained with the isoquinoline-based TSPO radioligand, [{sup 11}C]PK11195. Competition studies demonstrate that [{sup 11}C]SSR180575 has high specific binding for the TSPO. [{sup 11}C]SSR180575 is the first PET radioligand for the TSPO based on an indoleacetamide scaffold designed for imaging neuroinflammation in animal models and in the clinic. (orig.)

The role of rodents in the ecology of Ixodes ricinus and associated pathogens in Central and Eastern Europe.

Science.gov (United States)

Mihalca, Andrei D; Sándor, Attila D

2013-01-01

Rodents comprise more species than any other mammal order. Most rodents are considered keystone species in their ecological communities, hence the survival of many other species in the ecosystem depend on them. From medical point of view, this is particularly important for rodent-dependent pathogens. In the particular case of tick-borne diseases, rodents are important as hosts for vector ticks and as reservoir hosts (Lyme borreliosis, human granulocytic anaplasmosis, Crimean-Congo hemorrhagic fever, Tick-borne relapsing fevers, tick-borne rickettsioses, babesiosis). Community and population ecology of rodents was shown to be correlated with disease ecology in the case of many tick-borne diseases. In Eastern Europe, several adult hard-tick species use rodents as their principal hosts: Ixodes apronophorus, I. crenulatus, I. laguri, I. redikorzevi, I. trianguliceps. However, the majority of ticks feeding on rodents are immature stages of ticks which as adults are parasitic on larger mammals. Larvae and nymphs of Ixodes ricinus, the most abundant and medically important tick from Europe, are commonly found on rodents. This is particularly important, as many rodents are synanthropic and, together with other micromammals and birds are often the only available natural hosts for ticks in urban environments. This work reviews the correlated ecology of rodents and I. ricinus.

Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents

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Brink, Willem van den; Emerenciana, Annette [Systems Pharmacology, Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Medicines Evaluation Board, Utrecht (Netherlands); Bellanti, Francesco [Systems Pharmacology, Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Della Pasqua, Oscar [Systems Pharmacology, Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline, Stockley Park, Uxbridge (United Kingdom); Clinical Pharmacology & Therapeutics, UCL, School of Life and Medical Sciences, London (United Kingdom); Laan, Jan Willem van der, E-mail: jw.vd.laan@cbg-meb.nl [Division of Toxicology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Medicines Evaluation Board, Utrecht (Netherlands)

2017-04-01

Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2 years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes. - Highlights: • An integrative PKPD model is applied to

Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents

International Nuclear Information System (INIS)

Brink, Willem van den; Emerenciana, Annette; Bellanti, Francesco; Della Pasqua, Oscar; Laan, Jan Willem van der

2017-01-01

Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2 years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes. - Highlights: • An integrative PKPD model is applied to

Amyloid β Enhances Typical Rodent Behavior While It Impairs Contextual Memory Consolidation.

Science.gov (United States)

Salgado-Puga, Karla; Prado-Alcalá, Roberto A; Peña-Ortega, Fernando

2015-01-01

Alzheimer's disease (AD) is associated with an early hippocampal dysfunction, which is likely induced by an increase in soluble amyloid beta peptide (Aβ). This hippocampal failure contributes to the initial memory deficits observed both in patients and in AD animal models and possibly to the deterioration in activities of daily living (ADL). One typical rodent behavior that has been proposed as a hippocampus-dependent assessment model of ADL in mice and rats is burrowing. Despite the fact that AD transgenic mice show some evidence of reduced burrowing, it has not been yet determined whether or not Aβ can affect this typical rodent behavior and whether this alteration correlates with the well-known Aβ-induced memory impairment. Thus, the purpose of this study was to test whether or not Aβ affects burrowing while inducing hippocampus-dependent memory impairment. Surprisingly, our results show that intrahippocampal application of Aβ increases burrowing while inducing memory impairment. We consider that this Aβ-induced increase in burrowing might be associated with a mild anxiety state, which was revealed by increased freezing behavior in the open field, and conclude that Aβ-induced hippocampal dysfunction is reflected in the impairment of ADL and memory, through mechanisms yet to be determined.

Helminth Infections of Rodents and Their Zoonotic Importance in Boyer-Ahmad District, Southwestern Iran

OpenAIRE

RANJBAR, Mohammad Javad; SARKARI, Bahador; MOWLAVI, Gholam Reza; SEIFOLLAHI, Zeinab; MOSHFE, Abdolali; ABDOLAHI KHABISI, Samaneh; MOBEDI, Iraj

2017-01-01

AbstractBackground: Rodents are considered as reservoirs of various zoonotic diseases including helminthic infections. The current study aimed to evaluate the prevalence of helminth infections in rodents, in Boyer-Ahmad district, Southwestern Iran.Methods: Overall, 52 rodents were captured from various areas of the district by Sherman live traps. The animals were then euthanized and dissected. During necropsy, each organ was examined macroscopically for presence of any cyst or visible parasit...

Adaptation for rodent pollination in Leucospermum arenarium (Proteaceae) despite rapid pollen loss during grooming.

Science.gov (United States)

Johnson, Christopher Michael; Pauw, Anton

2014-05-01

Plants are adapted for rodent pollination in diverse and intricate ways. This study explores an extraordinary example of these adaptations in the pincushion Leucospermum arenarium (Proteaceae) from South Africa. Live trapping and differential exclusion experiments were used to test the role of rodents versus birds and insects as pollinators. To explore the adaptive significance of geoflory, inflorescences were raised above ground level and seed production was compared. Captive rodents and flowers with artificial stigmas were used to test the effect of grooming on the rate of pollen loss. Microscopy, nectar composition analysis and manipulative experiments were used to investigate the bizarre nectar production and transport system. Differential exclusion of rodents, birds and insects demonstrated the importance of rodents in promoting seed production. Live trapping revealed that hairy-footed gerbils, Gerbillurus paeba, and striped field mice, Rhabdomys pumilio, both carried L. arenarium pollen on their forehead and rostrum, but much larger quantities ended up in faeces as a result of grooming. Terrarium experiments showed that grooming exponentially diminished the pollen loads that they carried. The nectar of L. arenarium was found to be unusually viscous and to be presented in a novel location on the petal tips, where rodents could access it without destroying the flowers. Nectar was produced inside the perianth, but was translocated to the petal tips via capillary ducts. In common with many other rodent-pollinated plants, the flowers are presented at ground level, but when raised to higher positions seed production was not reduced, indicating that selection through female function does not drive the evolution of geoflory. Despite the apparent cost of pollen lost to grooming, L. arenarium has evolved remarkable adaptations for rodent pollination and provides the first case of this pollination system in the genus.

Serological Survey of Zoonotic Viruses in Invasive and Native Commensal Rodents in Senegal, West Africa.

Science.gov (United States)

Diagne, Christophe A; Charbonnel, Nathalie; Henttonen, Heikki; Sironen, Tarja; Brouat, Carine

2017-10-01

Increasing studies on rodent-borne diseases still highlight the major role of rodents as reservoirs of numerous zoonoses of which the frequency is likely to increase worldwide as a result of accelerated anthropogenic changes, including biological invasions. Such a situation makes pathogen detection in rodent populations important, especially in the context of developing countries characterized by high infectious disease burden. Here, we used indirect fluorescent antibody tests to describe the circulation of potentially zoonotic viruses in both invasive (Mus musculus domesticus and Rattus rattus) and native (Mastomys erythroleucus and Mastomys natalensis) murine rodent populations in Senegal (West Africa). Of the 672 rodents tested, we reported 22 seropositive tests for Hantavirus, Orthopoxvirus, and Mammarenavirus genera, and no evidence of viral coinfection. This study is the first to report serological detection of Orthopoxvirus in rodents from Senegal, Mammarenavirus in R. rattus from Africa, and Hantavirus in M. m. domesticus and in M. erythroleucus. Further specific identification of the viral agents highlighted here is urgently needed for crucial public health concerns.

Preclinical Magnetic Resonance Fingerprinting (MRF) at 7 T: Effective Quantitative Imaging for Rodent Disease Models

Science.gov (United States)

Gao, Ying; Chen, Yong; Ma, Dan; Jiang, Yun; Herrmann, Kelsey A.; Vincent, Jason A.; Dell, Katherine M.; Drumm, Mitchell L.; Brady-Kalnay, Susann M.; Griswold, Mark A.; Flask, Chris A.; Lu, Lan

2015-01-01

High field, preclinical magnetic resonance imaging (MRI) scanners are now commonly used to quantitatively assess disease status and efficacy of novel therapies in a wide variety of rodent models. Unfortunately, conventional MRI methods are highly susceptible to respiratory and cardiac motion artifacts resulting in potentially inaccurate and misleading data. We have developed an initial preclinical, 7.0 T MRI implementation of the highly novel Magnetic Resonance Fingerprinting (MRF) methodology that has been previously described for clinical imaging applications. The MRF technology combines a priori variation in the MRI acquisition parameters with dictionary-based matching of acquired signal evolution profiles to simultaneously generate quantitative maps of T1 and T2 relaxation times and proton density. This preclinical MRF acquisition was constructed from a Fast Imaging with Steady-state Free Precession (FISP) MRI pulse sequence to acquire 600 MRF images with both evolving T1 and T2 weighting in approximately 30 minutes. This initial high field preclinical MRF investigation demonstrated reproducible and differentiated estimates of in vitro phantoms with different relaxation times. In vivo preclinical MRF results in mouse kidneys and brain tumor models demonstrated an inherent resistance to respiratory motion artifacts as well as sensitivity to known pathology. These results suggest that MRF methodology may offer the opportunity for quantification of numerous MRI parameters for a wide variety of preclinical imaging applications. PMID:25639694

Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil’s Amazon Rainforest

Directory of Open Access Journals (Sweden)

Marcia J. Guimarães Marques

2018-01-01

Full Text Available Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials

Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil’s Amazon Rainforest

Science.gov (United States)

Guimarães Marques, Marcia J.; Reyes-Garcia, Selvin Z.; Marques-Carneiro, José E.; Lopes-Silva, Leonardo B.; Andersen, Monica L.; Cavalheiro, Esper A.; Scorza, Fulvio A.; Scorza, Carla A.

2018-01-01

Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed

Isolating human DNA repair genes using rodent-cell mutants

International Nuclear Information System (INIS)

Thompson, L.H.; Weber, C.A.; Brookman, K.W.; Salazar, E.P.; Stewart, S.A.; Mitchell, D.L.

1987-01-01

The DNA repair systems of rodent and human cells appear to be at least as complex genetically as those in lower eukaryotes and bacteria. The use of mutant lines of rodent cells as a means of identifying human repair genes by functional complementation offers a new approach toward studying the role of repair in mutagenesis and carcinogenesis. In each of six cases examined using hybrid cells, specific human chromosomes have been identified that correct CHO cell mutations affecting repair of damage from uv or ionizing radiations. This finding suggests that both the repair genes and proteins may be virtually interchangeable between rodent and human cells. Using cosmid vectors, human repair genes that map to chromosome 19 have cloned as functional sequences: ERCC2 and XRCC1. ERCC1 was found to have homology with the yeast excision repair gene RAD10. Transformants of repair-deficient cell lines carrying the corresponding human gene show efficient correction of repair capacity by all criteria examined. 39 refs., 1 fig., 1 tab

The Need for Speed in Rodent Locomotion Analyses

Science.gov (United States)

Batka, Richard J.; Brown, Todd J.; Mcmillan, Kathryn P.; Meadows, Rena M.; Jones, Kathryn J.; Haulcomb, Melissa M.

2016-01-01

Locomotion analysis is now widely used across many animal species to understand the motor defects in disease, functional recovery following neural injury, and the effectiveness of various treatments. More recently, rodent locomotion analysis has become an increasingly popular method in a diverse range of research. Speed is an inseparable aspect of locomotion that is still not fully understood, and its effects are often not properly incorporated while analyzing data. In this hybrid manuscript, we accomplish three things: (1) review the interaction between speed and locomotion variables in rodent studies, (2) comprehensively analyze the relationship between speed and 162 locomotion variables in a group of 16 wild-type mice using the CatWalk gait analysis system, and (3) develop and test a statistical method in which locomotion variables are analyzed and reported in the context of speed. Notable results include the following: (1) over 90% of variables, reported by CatWalk, were dependent on speed with an average R2 value of 0.624, (2) most variables were related to speed in a nonlinear manner, (3) current methods of controlling for speed are insufficient, and (4) the linear mixed model is an appropriate and effective statistical method for locomotion analyses that is inclusive of speed-dependent relationships. Given the pervasive dependency of locomotion variables on speed, we maintain that valid conclusions from locomotion analyses cannot be made unless they are analyzed and reported within the context of speed. PMID:24890845

A higher-taxon approach to rodent conservation priorities for the 21st century

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Amori, G.

2003-12-01

Full Text Available Although rodents are not considered among the most threatened mammals, there is ample historical evidence concerning the vulnerability to extinction of several rodent phylogenetic lineages. Owing to the high number of species, poor taxonomy and the lack of detailed information on population status, the assessment of threat status according to IUCN criteria has still to be considered arbitrary in some cases. Public appreciation is scarce and tends to overlook the ecological role and conservation problems of an order representing about 41 percent of mammalian species. We provide an overview of the most relevant information concerning the conservation status of rodents at the genus, subfamily, and family level. For species¿poor taxa, the importance of distinct populations is highlighted and a splitter approach in taxonomy is adopted. Considering present constraints, strategies for the conservation of rodent diversity must rely mainly on higher taxon and hot-spot approaches. A clear understanding of phyletic relationships among difficult groups -such as Rattus, for instance- is an urgent goal. Even if rodent taxonomy is still unstable, high taxon approach is amply justified from a conservation standpoint as it offers a more subtle overview of the world terrestrial biodiversity than that offered by large mammals. Of the circa 451 living rodent genera, 126 (27,9 %, representing 168 living species, deserve conservation attention according to the present study. About 76 % of genera at risk are monotypic, confirming the danger of losing a considerable amount of phylogenetic distinctiveness.

Allometric disparity in rodent evolution

OpenAIRE

Wilson LAB

2013-01-01

In this study, allometric trajectories for 51 rodent species, comprising equal representatives from each of the major clades (Ctenohystrica, Muroidea, Sciuridae), are compared in a multivariate morphospace (=allometric space) to quantify magnitudes of disparity in cranial growth. Variability in allometric trajectory patterns was compared to measures of adult disparity in each clade, and dietary habit among the examined species, which together encapsulated an ecomorphological breadth. Results ...

Genotyping and subtyping of Giardia and Cryptosporidium isolates from commensal rodents in China.

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Zhao, Z; Wang, R; Zhao, W; Qi, M; Zhao, J; Zhang, L; Li, J; Liu, A

2015-05-01

Cryptosporidium and Giardia are two important zoonotic intestinal parasites responsible for diarrhoea in humans and other animals worldwide. Rodents, as reservoirs or carriers of Cryptosporidium and Giardia, are abundant and globally widespread. In the present study, we collected 232 fecal specimens from commensal rodents captured in animal farms and farm neighbourhoods in China. We collected 33 Asian house rats, 168 brown rats and 31 house mice. 6.0% (14/232) and 8.2% (19/232) of these rodents were microscopy-positive for Giardia cysts and Cryptosporidium oocysts, respectively. All 14 Giardia isolates were identified as Giardia duodenalis assemblage G at a minimum of one or maximum of three gene loci (tpi, gdh and bg). By small subunit rRNA (SSU rRNA) gene sequencing, Cryptosporidium parvum (n = 12) and Cryptosporidium muris (n = 7) were identified. The gp60 gene encoding the 60-kDa glycoprotein was successfully amplified and sequenced in nine C. parvum isolates, all of which belonged to the IIdA15G1 subtype. Observation of the same IIdA15G1 subtype in humans (previously) and in rodents (here) suggests that rodents infected with Cryptosporidium have the potential to transmit cryptosporidiosis to humans.

In vivo microCT imaging of rodent cerebral vasculature

International Nuclear Information System (INIS)

Seo, Youngho; Hasegawa, Bruce H; Hashimoto, Tomoki; Nuki, Yoshitsugu

2008-01-01

Computed tomography (CT) remains a critical diagnostic tool for evaluating patients with cerebrovascular disease, and the advent of specialized systems for imaging rodents has extended these techniques to small animal models of these diseases. We therefore have evaluated in vivo methods of imaging rat models of hemorrhagic stroke using a high resolution compact computed tomography ('microCT') system (FLEX(tm) X-O(tm), Gamma Medica-Ideas, Northridge, CA). For all in vivo studies, the head of the anesthetized rat was secured in a custom immobilization device for microCT imaging with 512 projections over 2 min at 60 kVp and 0.530 mA (I tube x t/rotation = 63.6 mAs). First, imaging without iodinated contrast was performed (a) to differentiate the effect of contrast agent in contrast-enhanced CT and (b) to examine the effectiveness of the immobilization device between two time points of CT acquisitions. Then, contrast-enhanced CT was performed with continuous administration of iopromide (300 mgI ml -1 at 1.2 ml min -1 ) to visualize aneurysms and other vascular formations in the carotid and cerebral arteries that may precede subarachnoid hemorrhage. The accuracy of registration between the noncontrast and contrast-enhanced CT images with the immobilization device was compared against the images aligned with normalized mutual information using FMRIB's linear image registration tool (FLIRT). Translations and rotations were examined between the FLIRT-aligned noncontrast CT image and the nonaligned noncontrast CT image. These two data sets demonstrated translational and rotational differences of less than 0.5 voxel (∼85 μm) and 0.5 deg., respectively. Noncontrast CT demonstrated a very small volume (0.1 ml) of femoral arterial blood introduced surgically into the rodent brain. Continuous administration of iopromide during the CT acquisition produced consistent vascular contrast in the reconstructed CT images. As a result, carotid arteries and major cerebral blood vessels

In vivo microCT imaging of rodent cerebral vasculature

Energy Technology Data Exchange (ETDEWEB)

Seo, Youngho; Hasegawa, Bruce H [Center for Molecular and Functional Imaging, Department of Radiology, University of California, San Francisco, CA 94143 (United States); Hashimoto, Tomoki; Nuki, Yoshitsugu [Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143 (United States)], E-mail: youngho.seo@radiology.ucsf.edu

2008-04-07

Computed tomography (CT) remains a critical diagnostic tool for evaluating patients with cerebrovascular disease, and the advent of specialized systems for imaging rodents has extended these techniques to small animal models of these diseases. We therefore have evaluated in vivo methods of imaging rat models of hemorrhagic stroke using a high resolution compact computed tomography ('microCT') system (FLEX(tm) X-O(tm), Gamma Medica-Ideas, Northridge, CA). For all in vivo studies, the head of the anesthetized rat was secured in a custom immobilization device for microCT imaging with 512 projections over 2 min at 60 kVp and 0.530 mA (I{sub tube} x t/rotation = 63.6 mAs). First, imaging without iodinated contrast was performed (a) to differentiate the effect of contrast agent in contrast-enhanced CT and (b) to examine the effectiveness of the immobilization device between two time points of CT acquisitions. Then, contrast-enhanced CT was performed with continuous administration of iopromide (300 mgI ml{sup -1} at 1.2 ml min{sup -1}) to visualize aneurysms and other vascular formations in the carotid and cerebral arteries that may precede subarachnoid hemorrhage. The accuracy of registration between the noncontrast and contrast-enhanced CT images with the immobilization device was compared against the images aligned with normalized mutual information using FMRIB's linear image registration tool (FLIRT). Translations and rotations were examined between the FLIRT-aligned noncontrast CT image and the nonaligned noncontrast CT image. These two data sets demonstrated translational and rotational differences of less than 0.5 voxel ({approx}85 {mu}m) and 0.5 deg., respectively. Noncontrast CT demonstrated a very small volume (0.1 ml) of femoral arterial blood introduced surgically into the rodent brain. Continuous administration of iopromide during the CT acquisition produced consistent vascular contrast in the reconstructed CT images. As a result, carotid

Neuroimmune Pathways in Alcohol Consumption: Evidence from Behavioral and Genetic Studies in Rodents and Humans

Science.gov (United States)

Robinson, Gizelle; Most, Dana; Ferguson, Laura B.; Mayfield, Jody; Harris, R. Adron; Blednov, Yuri A.

2014-01-01

Immune or brain proinflammatory signaling has been linked to some of the behavioral effects of alcohol. Immune signaling appears to regulate voluntary ethanol intake in rodent models, and ethanol intake activates the immune system in multiple models. This bidirectional link raises the possibility that consumption increases immune signaling, which in turn further increases consumption in a feed-forward cycle. Data from animal and human studies provide overlapping support for the involvement of immune-related genes and proteins in alcohol action, and combining animal and human data is a promising approach to systematically evaluate and nominate relevant pathways. Based on rodent models, neuroimmune pathways may represent unexplored, nontraditional targets for medication development to reduce alcohol consumption and prevent relapse. Peroxisome proliferator-activated receptor agonists are one class of anti-inflammatory medications that demonstrate antiaddictive properties for alcohol and other drugs of abuse. Expression of immune-related genes is altered in animals and humans following chronic alcohol exposure, and the regulatory influences of specific mRNAs, microRNAs, and activated cell types are areas of intense study. Ultimately, the use of multiple datasets combined with behavioral validation will be needed to link specific neuroimmune pathways to addiction vulnerability. PMID:25175860

Effects of anatomy and diet on gastrointestinal pH in rodents.

Science.gov (United States)

Kohl, Kevin D; Stengel, Ashley; Samuni-Blank, Michal; Dearing, M Denise

2013-04-01

The pH of the gastrointestinal tract can have profound influences on digestive processes. Rodents exhibit wide variation in both stomach morphology and dietary strategies, both of which may influence gut pH. Various rodent species have evolved bilocular (or semi-segmented) stomachs that may allow for more microbial growth compared to unilocular (single-chambered) stomachs. Additionally, herbivory has evolved multiple times in rodents. The high dietary fiber typical of an herbivorous diet is known to induce secretion of bicarbonate in the gut. We predicted that stomach segmentation might facilitate the separation of contents in the proximal chamber from that of the gastric stomach, facilitating a chemical environment suitable to microbial growth. To investigate the effect of stomach anatomy and diet on gut pH, several species of rodent with varying stomach morphology were fed either a high or low-fiber diet for 7 days, and pH of the proximal stomach, gastric stomach, small intestine, and cecum were measured. We discovered that rodents with bilocular stomach anatomy maintained a larger pH gradient between the proximal and gastric stomach compartments, and were able to achieve a lower absolute gastric pH compared to those with unilocular stomachs. Dietary fiber increased the pH of the small intestine, but not in any other gut regions. The stomach pH data supports the century old hypothesis that bilocular stomach anatomy creates an environment in the proximal stomach that is suitable for microbial growth. Additionally, the alkaline small intestinal pH on a high fiber diet may enhance digestion. Copyright © 2013 Wiley Periodicals, Inc.

Fire ignition during laser surgery in pet rodents

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Collarile Tommaso

2012-09-01

Full Text Available Abstract Background Laser surgery is an attractive alternative to other means of section device in terms of tissue inflammation and interaction, which has been extensively used in human and veterinary medicine. Although accidental ignition during laser surgeries is sporadically reported in human medical literature, to the authors’ knowledge this is the first report regarding laser-dependent fire ignition during surgery in veterinary medicine. Case presentation Two rodents, a 13-month old, 27-gram, male pet mouse (Mus musculus and a 1-year old, female Russian hamster (Phodopus sungorus, underwent surgical removal of masses with diode laser. During the surgical procedures fires ignited from the face masks. The mouse presented severe burns on the head and both forelimbs, it was hospitalized and approximately 2 months after surgery burns were resolved. The hamster presented severe burns on the face and the proximal regions of the body. At 72 hours from the accident the hamster was euthanized. Conclusion The present report suggests that fire ignition is a potential life-threatening complication of laser surgery in non-intubated rodents maintained under volatile anesthesia. High oxygen concentrations, the presence of combustible, and the narrowness of the surgical field with the face mask during laser surgery on rodents are risk factors for fire ignition.

Respiratory insufficiency correlated strongly with mortality of rodents infected with West Nile virus.

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John D Morrey

Full Text Available West Nile virus (WNV disease can be fatal for high-risk patients. Since WNV or its antigens have been identified in multiple anatomical locations of the central nervous system of persons or rodent models, one cannot know where to investigate the actual mechanism of mortality without careful studies in animal models. In this study, depressed respiratory functions measured by plethysmography correlated strongly with mortality. This respiratory distress, as well as reduced oxygen saturation, occurred beginning as early as 4 days before mortality. Affected medullary respiratory control cells may have contributed to the animals' respiratory insufficiency, because WNV antigen staining was present in neurons located in the ventrolateral medulla. Starvation or dehydration would be irrelevant in people, but could cause death in rodents due to lethargy or loss of appetite. Animal experiments were performed to exclude this possibility. Plasma ketones were increased in moribund infected hamsters, but late-stage starvation markers were not apparent. Moreover, daily subcutaneous administration of 5% dextrose in physiological saline solution did not improve survival or other disease signs. Therefore, infected hamsters did not die from starvation or dehydration. No cerebral edema was apparent in WNV- or sham-infected hamsters as determined by comparing wet-to-total weight ratios of brains, or by evaluating blood-brain-barrier permeability using Evans blue dye penetration into brains. Limited vasculitis was present in the right atrium of the heart of infected hamsters, but abnormal electrocardiograms for several days leading up to mortality did not occur. Since respiratory insufficiency was strongly correlated with mortality more than any other pathological parameter, it is the likely cause of death in rodents. These animal data and a poor prognosis for persons with respiratory insufficiency support the hypothesis that neurological lesions affecting respiratory

Light rescues circadian behavior and brain dopamine abnormalities in diurnal rodents exposed to a winter-like photoperiod

NARCIS (Netherlands)

Itzhacki, Jacob; Clesse, Daniel; Goumon, Yannick; Van Someren, Eus J; Mendoza, Jorge

2018-01-01

Seasonal affective disorder (SAD), beyond mood changes, is characterized by alterations in daily rhythms of behavior and physiology. The pathophysiological conditions of SAD involve changes in day length and its first-line treatment is bright light therapy. Animal models using nocturnal rodents have

Identification of collected ectoparasites of rodents in the west of Khuzestan Province (Ahvaz and Hovizeh, southwest of Iran

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Mahmood Rahdar

2015-08-01

Full Text Available Objective: To determine possible parasitic arthropods fauna in certain rodent species in the west of Khuzestan Province including Ahvaz and its suburb and suburb of Hovizeh, southwest of Iran. Methods: In the current study Sherman live traps were used to catch the rodents. The rodents were identified using Iranian keys of rodents. The ectoparasites were picked up in different ways from bodies of the anesthetized rodents and stored in 70% ethanol to preserve and identified using international keys. Results: In the present study 3 species and 4 genera of ectoparasites and 4 species of rodents were identified. Conclusions: It is important to explain that the great ectoparasite biodiversity in the west of Khuzestan, with small sampling of rodents, described a high risk factor to transmit the different infectious diseases among domestic animals and humans.

Transformation of the rodent malaria parasite Plasmodium chabaudi.

Science.gov (United States)

Spence, Philip J; Cunningham, Deirdre; Jarra, William; Lawton, Jennifer; Langhorne, Jean; Thompson, Joanne

2011-04-01

The rodent malaria parasite Plasmodium chabaudi chabaudi shares many features with human malaria species, including P. falciparum, and is the in vivo model of choice for many aspects of malaria research in the mammalian host, from sequestration of parasitized erythrocytes, to antigenic variation and host immunity and immunopathology. This protocol describes an optimized method for the transformation of mature blood-stage P.c. chabaudi and a description of a vector that targets efficient, single crossover integration into the P.c. chabaudi genome. Transformed lines are reproducibly generated and selected within 14-20 d, and show stable long-term protein expression even in the absence of drug selection. This protocol, therefore, provides the scientific community with a robust and reproducible method to generate transformed P.c. chabaudi parasites expressing fluorescent, bioluminescent and model antigens that can be used in vivo to dissect many of the fundamental principles of malaria infection.

Gender differences in the induction of chromosomal aberrations and gene mutations in rodent germ cells

International Nuclear Information System (INIS)

Adler, Ilse-Dore; Carere, Angelo; Eichenlaub-Ritter, Ursula; Pacchierotti, Francesca

2007-01-01

Germ cell mutagenicity testing provides experimental data to quantify genetic risk for exposed human populations. The majority of tests are performed with exposure of males, and female data are relatively rare. The reason for this paucity lies in the differences between male and female germ cell biology. Male germ cells are produced throughout reproductive life and all developmental stages can be ascertained by appropriate breeding schemes. In contrast, the female germ cell pool is limited, meiosis begins during embryogenesis and oocytes are arrested over long periods of time until maturation processes start for small numbers of oocytes during the oestrus cycle in mature females. The literature data are reviewed to point out possible gender differences of germ cells to exogenous agents such as chemicals or ionizing radiation. From the limited information, it can be concluded that male germ cells are more sensitive than female germ cells to the induction of chromosomal aberrations and gene mutations. However, exceptions are described which shed doubt on the extrapolation of experimental data from male rodents to the genetic risk of the human population. Furthermore, the female genome may be more sensitive to mutation induction during peri-conceptional stages compared to the male genome of the zygote. With few exceptions, germ cell experiments have been carried out under high acute exposure to optimize the effects and to compensate for the limited sample size in animal experiments. Human exposure to environmental agents, on the other hand, is usually chronic and involves low doses. Under these conditions, gender differences may become apparent that have not been studied so far. Additionally, data are reviewed that suggest a false impression of safety when responses are negative under high acute exposure of male rodents while a mutational response is induced by low chronic exposure. The classical (morphological) germ cell mutation tests are not performed anymore

Obesidade induzida por consumo de dieta: modelo em roedores para o estudo dos distúrbios relacionados com a obesidade Diet-induced obesity: rodent model for the study of obesity-related disorders

Directory of Open Access Journals (Sweden)

Tiago Campos Rosini

2012-06-01

mostly to genetic mutations, but this model is far from that found in humans. The use of hypercaloric or hyperlipidemic diets has been used as a model of obesity induction in animals, because of its similarity to the genesis and metabolic responses caused by obesity in humans. The objective of this review is to show the different types of diets used to induce obesity in rodents, the induced metabolic alterations, and to identify some points that should be taken into account so that the model can be effective for the study of obesity-related complications. A search was performed in the PubMed database using the following keywords: 1- "hypercaloric diet" AND "rodent", 2- "hyperlipidic diet" AND "rodent", selecting those considered the most relevant according to the following criteria: date of publication (1995-2011; the use of wild-type animals; detailed description of the diet used and analysis of biochemical and vascular parameters of interest. References were included to introduce subjects such as the increased prevalence of obesity and questions related to the genesis of obesity in humans. The model of diet-induced obesity in rodents can be considered effective when the objective is the study of the physiopathology of metabolic and vascular complications associated with obesity.

Quantitative Assessment of Mammary Gland Density in Rodents Using Digital Image Analysis

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Thompson Henry J

2011-06-01

Full Text Available Abstract Background Rodent models have been used extensively to study mammary gland development and for studies of toxicology and carcinogenesis. Mammary gland gross morphology can visualized via the excision of intact mammary gland chains following fixation and staining with carmine using a tissue preparation referred to as a whole mount. Methods are described for the automated collection of digital images from an entire mammary gland whole mount and for the interrogation of digital data using a "masking" technique available with Image-Pro® plus image analysis software (Mediacybernetics. Silver Spring, MD. Results Parallel to mammographic analysis in humans, measurements of rodent mammary gland density were derived from area-based or volume-based algorithms and included: total circumscribed mammary fat pad mass, mammary epithelial mass, and epithelium-free fat pad mass. These values permitted estimation of absolute mass of mammary epithelium as well as breast density. The biological plausibility of these measurements was evaluated in mammary whole mounts from rats and mice. During mammary gland development, absolute epithelial mass increased linearly without significant changes in mammographic density. Treatment of rodents with tamoxifen, 9-cis-retinoic acid, or ovariectomy, and occurrence of diet induced obesity decreased both absolute epithelial mass and mammographic density. The area and volumetric methods gave similar results. Conclusions Digital image analysis can be used for screening agents for potential impact on reproductive toxicity or carcinogenesis as well as for mechanistic studies, particularly for cumulative effects on mammary epithelial mass as well as translational studies of mechanisms that explain the relationship between epithelial mass and cancer risk.

Acute ingestion dosimetry using the ICRP 30 gastrointestinal tract model

International Nuclear Information System (INIS)

Cassels, B.M.

1987-01-01

This paper examines the gastrointestinal (GI) tract model used for dosimetry as outlined in ICRP30, to allow quick calculations of effective dose equivalents for acute radionuclide ingestion. A computer program has been developed to emulate the GI tract model. The program and associated data files are structured so that the GI tract model parameters can be varied, while the file structure and algorithm for the GI tract model should require minimal modification to allow the same theories that apply in this model to be used for other dosimetric models

The Development of a Machine Learning Inpatient Acute Kidney Injury Prediction Model.

Science.gov (United States)

Koyner, Jay L; Carey, Kyle A; Edelson, Dana P; Churpek, Matthew M

2018-03-28

To develop an acute kidney injury risk prediction model using electronic health record data for longitudinal use in hospitalized patients. Observational cohort study. Tertiary, urban, academic medical center from November 2008 to January 2016. All adult inpatients without pre-existing renal failure at admission, defined as first serum creatinine greater than or equal to 3.0 mg/dL, International Classification of Diseases, 9th Edition, code for chronic kidney disease stage 4 or higher or having received renal replacement therapy within 48 hours of first serum creatinine measurement. None. Demographics, vital signs, diagnostics, and interventions were used in a Gradient Boosting Machine algorithm to predict serum creatinine-based Kidney Disease Improving Global Outcomes stage 2 acute kidney injury, with 60% of the data used for derivation and 40% for validation. Area under the receiver operator characteristic curve (AUC) was calculated in the validation cohort, and subgroup analyses were conducted across admission serum creatinine, acute kidney injury severity, and hospital location. Among the 121,158 included patients, 17,482 (14.4%) developed any Kidney Disease Improving Global Outcomes acute kidney injury, with 4,251 (3.5%) developing stage 2. The AUC (95% CI) was 0.90 (0.90-0.90) for predicting stage 2 acute kidney injury within 24 hours and 0.87 (0.87-0.87) within 48 hours. The AUC was 0.96 (0.96-0.96) for receipt of renal replacement therapy (n = 821) in the next 48 hours. Accuracy was similar across hospital settings (ICU, wards, and emergency department) and admitting serum creatinine groupings. At a probability threshold of greater than or equal to 0.022, the algorithm had a sensitivity of 84% and a specificity of 85% for stage 2 acute kidney injury and predicted the development of stage 2 a median of 41 hours (interquartile range, 12-141 hr) prior to the development of stage 2 acute kidney injury. Readily available electronic health record data can be used

Recovering 'lost' information in the presence of noise: application to rodent-predator dynamics

International Nuclear Information System (INIS)

Smelyanskiy, V N; Luchinsky, D G; Millonas, M M; McClintock, P V E

2009-01-01

A Hamiltonian approach is introduced for the reconstruction of trajectories and models of complex stochastic dynamics from noisy measurements. The method converges even when entire trajectory components are unobservable and the parameters are unknown. It is applied to reconstruct nonlinear models of rodent-predator oscillations in Finnish Lapland and high-Arctic tundra. The projected character of noisy incomplete measurements is revealed and shown to result in a degeneracy of the likelihood function within certain null-spaces. The performance of the method is compared with that of the conventional Markov chain Monte Carlo (MCMC) technique.

Survey for hantaviruses, tick-borne encephalitis virus, and Rickettsia spp. in small rodents in Croatia.

Science.gov (United States)

Svoboda, Petra; Dobler, Gerhard; Markotić, Alemka; Kurolt, Ivan-Christian; Speck, Stephanie; Habuš, Josipa; Vucelja, Marko; Krajinović, Lidija Cvetko; Tadin, Ante; Margaletić, Josip; Essbauer, Sandra

2014-07-01

In Croatia, several rodent- and vector-borne agents are endemic and of medical importance. In this study, we investigated hantaviruses and, for the first time, tick-borne encephalitis virus (TBEV) and Rickettsia spp. in small wild rodents from two different sites (mountainous and lowland region) in Croatia. In total, 194 transudate and tissue samples from 170 rodents (A. flavicollis, n=115; A. agrarius, n=2; Myodes glareolus, n=53) were tested for antibodies by indirect immunofluorescence assays (IIFT) and for nucleic acids by conventional (hantaviruses) and real-time RT-/PCRs (TBEV and Rickettsia spp.). A total of 25.5% (24/94) of the rodents from the mountainous area revealed specific antibodies against hantaviruses. In all, 21.3% (20/94) of the samples from the mountainous area and 29.0% (9/31) from the lowland area yielded positive results for either Puumala virus (PUUV) or Dobrava-Belgrade virus (DOBV) using a conventional RT-PCR. All processed samples (n=194) were negative for TBEV by IIFT or real-time RT-PCR. Serological evidence of rickettsial infection was detected in 4.3% (4/94) rodents from the mountainous region. Another 3.2% (3/94) rodents were positive for Rickettsia spp. by real-time PCR. None of the rodents (n=76) from the lowland area were positive for Rickettsia spp. by real-time PCR. Dual infection of PUUV and Rickettsia spp. was found in one M. glareolus from the mountainous area by RT-PCR and real-time PCR, respectively. To our knowledge, this is the first detection of Rickettsia spp. in small rodents from Croatia. Phylogenetic analyses of S- and M-segment sequences obtained from the two study sites revealed well-supported subgroups in Croatian PUUV and DOBV. Although somewhat limited, our data showed occurrence and prevalence of PUUV, DOBV, and rickettsiae in Croatia. Further studies are warranted to confirm these data and to determine the Rickettsia species present in rodents in these areas.

Dendrimer-driven neurotrophin expression differs in temporal patterns between rodent and human stem cells.

Science.gov (United States)

Shakhbazau, Antos; Shcharbin, Dzmitry; Seviaryn, Ihar; Goncharova, Natalya; Kosmacheva, Svetlana; Potapnev, Mihail; Bryszewska, Maria; Kumar, Ranjan; Biernaskie, Jeffrey; Midha, Rajiv

2012-05-07

This study reports the use of a nonviral expression system based on polyamidoamine dendrimers for time-restricted neurotrophin overproduction in mesenchymal stem cells and skin precursor-derived Schwann cells. The dendrimers were used to deliver plasmids for brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) expression in both rodent and human stem cells, and the timelines of expression were studied. We have found that, despite the fact that transfection efficiencies and protein expression levels were comparable, dendrimer-driven expression in human mesenchymal stem cells was characterized by a more rapid decline compared to rodent cells. Transient expression systems can be beneficial for some neurotrophins, which were earlier reported to cause unwanted side effects in virus-based long-term expression models. Nonviral neurotrophin expression is a biologically safe and accessible alternative to increase the therapeutic potential of autologous adult stem cells and stem cell-derived functional differentiated cells.

The selective orexin receptor 1 antagonist ACT-335827 in a rat model of diet-induced obesity associated with metabolic syndrome

OpenAIRE

Steiner, Michel A.; Sciarretta, Carla; Pasquali, Anne; Jenck, Francois

2013-01-01

The orexin system regulates feeding, nutrient metabolism and energy homeostasis. Acute pharmacological blockade of orexin receptor 1 (OXR-1) in rodents induces satiety and reduces normal and palatable food intake. Genetic OXR-1 deletion in mice improves hyperglycemia under high-fat (HF) diet conditions. Here we investigated the effects of chronic treatment with the novel selective OXR-1 antagonist ACT-335827 in a rat model of diet-induced obesity (DIO) associated with metabolic syndrome (MetS...

Forest rodents provide directed dispersal of Jeffrey pine seeds

Science.gov (United States)

Briggs, J.S.; Wall, S.B.V.; Jenkins, S.H.

2009-01-01

Some species of animals provide directed dispersal of plant seeds by transporting them nonrandomly to microsites where their chances of producing healthy seedlings are enhanced. We investigated whether this mutualistic interaction occurs between granivorous rodents and Jeffrey pine (Pinus jeffreyi) in the eastern Sierra Nevada by comparing the effectiveness of random abiotic seed dispersal with the dispersal performed by four species of rodents: deer mice (Peromyscus maniculatus), yellow-pine and long-eared chipmunks (Tamias amoenus and T. quadrimaculatus), and golden-mantled ground squirrels (Spermophilus lateralis). We conducted two caching studies using radio-labeled seeds, the first with individual animals in field enclosures and the second with a community of rodents in open forest. We used artificial caches to compare the fates of seeds placed at the range of microsites and depths used by animals with the fates of seeds dispersed abiotically. Finally, we examined the distribution and survival of naturally establishing seedlings over an eight-year period.Several lines of evidence suggested that this community of rodents provided directed dispersal. Animals preferred to cache seeds in microsites that were favorable for emergence or survival of seedlings and avoided caching in microsites in which seedlings fared worst. Seeds buried at depths typical of animal caches (5–25 mm) produced at least five times more seedlings than did seeds on the forest floor. The four species of rodents differed in the quality of dispersal they provided. Small, shallow caches made by deer mice most resembled seeds dispersed by abiotic processes, whereas many of the large caches made by ground squirrels were buried too deeply for successful emergence of seedlings. Chipmunks made the greatest number of caches within the range of depths and microsites favorable for establishment of pine seedlings. Directed dispersal is an important element of the population dynamics of Jeffrey pine, a

Effect of peripheral morphine in a human model of acute inflammatory pain

DEFF Research Database (Denmark)

Lillesø, J; Hammer, N A; Pedersen, J L

2000-01-01

Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

Leptospira interrogans in Rodents from Cape Verde.

Science.gov (United States)

Plata-Luis, Josué; Foronda, Pilar; Martín-Alonso, Aaron; Feliu, Carlos; Alves, Joana; Gil, Horacio; Valladares, Basilio

2016-11-01

Leptospirosis is an important worldwide zoonotic disease that can infect both animals and humans. In most cases, leptospirosis is a nonspecific self-limiting illness, but some patients can develop a severe form with a high mortality. This study was carried out in Santiago Island, Cape Verde, in 2012-2013. A total of 62 wild rodents (Rattus rattus and Mus domesticus) were analyzed. The lipL32 gene, present only in pathogenic Leptospira spp., was amplified by PCR, and 16 samples were positive (25.8%). In both rodent species, Leptospira interrogans was identified. The results show the presence of pathogenic Leptospira in the three localities analyzed in Santiago. The presence of L. interrogans demonstrates a serious health risk for the population, since this species has been associated with the most severe form of leptospirosis, the Weil's disease in humans, a severe infection with jaundice, renal failure, and hemorrhage.

Rodent movements, densities and radionuclide concentrations at a liquid radioactive waste disposal area

International Nuclear Information System (INIS)

Halford, D.K.

1983-01-01

Movements and densities of rodents at a liquid radioactive waste disposal area were studied from June to September 1981 using trap line and assessment line techniques. The average distance between points of successive capture was 42 +- 25 (SD) m for deer mice (Peromyscus maniculatus) and 37 +- 21 m for kangaroo rats (Dipodomys ordii). Densities of deer mice averaged 10.2/ha with a population estimate of 57 within the area of rodent captures. The population estimate of 4 species of small mammals at the waste pond complex was 93. Radionuclide concentrations averaged 133 +- 97 pCi/g for rodents captured inside the disposal area boundary, 18 +- 22 pCi/g for those captured outside of the dispoal area fence and 0.50 +- 0.6 pCi/g for control animals. Species captured outside of the waste area boundary had significantly lower (P 137 Cs, 134 Cs, 60 Co and 65 Zn) in rodents at the liquid waste disposal area was estimated to be about 162 nCi

The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia.

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Hvoslef-Eide, M; Mar, A C; Nilsson, S R O; Alsiö, J; Heath, C J; Saksida, L M; Robbins, T W; Bussey, T J

2015-11-01

The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.

Indirect effects of rodents on arthropods in a Scandinavian boreal forest

OpenAIRE

Malá, Barbora

2016-01-01

Rodents in boreal forest are an important component of food webs. Their role as drivers of the boreal forest ecosystem is debated. As herbivores they affect plant communities and alter qualities of plants. Consequently availability of food resources for other herbivorous species is altered. In my thesis I studied whether rodents indirectly influence communities of arthropods via plant resources. It is assumed that phytophagous arthropods respond to changes in plant resources by different feed...

Endotoxin, Coliform, and Dust Levels in Various Types of Rodent Bedding

OpenAIRE

Whiteside, Tanya E; Thigpen, Julius E; Kissling, Grace E; Grant, Mary G; Forsythe, Diane B

2010-01-01

Endotoxins in grain dust, household dust, and animal bedding may induce respiratory symptoms in rodents and humans. We assayed the endotoxin, coliform, and dust levels in 20 types of rodent bedding. Endotoxin concentrations were measured by using a commercial test kit, coliform counts were determined by using conventional microbiologic procedures, and dust content was evaluated by using a rotating–tapping shaker. Paper bedding types contained significantly less endotoxin than did other beddin...

Prenatal stressors in rodents: Effects on behavior

Directory of Open Access Journals (Sweden)

Marta Weinstock

2017-02-01

Full Text Available The current review focuses on studies in rodents published since 2008 and explores possible reasons for any differences they report in the effects of gestational stress on various types of behavior in the offspring. An abundance of experimental data shows that different maternal stressors in rodents can replicate some of the abnormalities in offspring behavior observed in humans. These include, anxiety, in juvenile and adult rats and mice, assessed in the elevated plus maze and open field tests and depression, detected in the forced swim and sucrose-preference tests. Deficits were reported in social interaction that is suggestive of pathology associated with schizophrenia, and in spatial learning and memory in adult rats in the Morris water maze test, but in most studies only males were tested. There were too few studies on the novel object recognition test at different inter-trial intervals to enable a conclusion about the effect of prenatal stress and whether any deficits are more prevalent in males. Among hippocampal glutamate receptors, NR2B was the only subtype consistently reduced in association with learning deficits. However, like in humans with schizophrenia and depression, prenatal stress lowered hippocampal levels of BDNF, which were closely correlated with decreases in hippocampal long-term potentiation. In mice, down-regulation of BDNF appeared to occur through the action of gene-methylating enzymes that are already increased above controls in prenatally-stressed neonates. In conclusion, the data obtained so far from experiments in rodents lend support to a physiological basis for the neurodevelopmental hypothesis of schizophrenia and depression.

Euthanasia using gaseous agents in laboratory rodents.

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Valentim, A M; Guedes, S R; Pereira, A M; Antunes, L M

2016-08-01

Several questions have been raised in recent years about the euthanasia of laboratory rodents. Euthanasia using inhaled agents is considered to be a suitable aesthetic method for use with a large number of animals simultaneously. Nevertheless, its aversive potential has been criticized in terms of animal welfare. The data available regarding the use of carbon dioxide (CO2), inhaled anaesthetics (such as isoflurane, sevoflurane, halothane and enflurane), as well as carbon monoxide and inert gases are discussed throughout this review. Euthanasia of fetuses and neonates is also addressed. A table listing currently available information to ease access to data regarding euthanasia techniques using gaseous agents in laboratory rodents was compiled. Regarding better animal welfare, there is currently insufficient evidence to advocate banning or replacing CO2 in the euthanasia of rodents; however, there are hints that alternative gases are more humane. The exposure to a volatile anaesthetic gas before loss of consciousness has been proposed by some scientific studies to minimize distress; however, the impact of such a measure is not clear. Areas of inconsistency within the euthanasia literature have been highlighted recently and stem from insufficient knowledge, especially regarding the advantages of the administration of isoflurane or sevoflurane over CO2, or other methods, before loss of consciousness. Alternative methods to minimize distress may include the development of techniques aimed at inducing death in the home cage of animals. Scientific outcomes have to be considered before choosing the most suitable euthanasia method to obtain the best results and accomplish the 3Rs (replacement, reduction and refinement). © The Author(s) 2015.

Discovery of Novel Alphacoronaviruses in European Rodents and Shrews

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Theocharis Tsoleridis

2016-03-01

Full Text Available Eight hundred and thirteen European rodents and shrews encompassing seven different species were screened for alphacoronaviruses using PCR detection. Novel alphacoronaviruses were detected in the species Rattus norvegicus, Microtus agrestis, Sorex araneus and Myodes glareolus. These, together with the recently described Lucheng virus found in China, form a distinct rodent/shrew-specific clade within the coronavirus phylogeny. Across a highly conserved region of the viral polymerase gene, the new members of this clade were up to 22% dissimilar at the nucleotide level to the previously described Lucheng virus. As such they might represent distinct species of alphacoronaviruses. These data greatly extend our knowledge of wildlife reservoirs of alphacoronaviruses.

Short interspersed elements (SINEs) of the Geomyoidea superfamily rodents.

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Gogolevsky, Konstantin P; Kramerov, Dmitri A

2006-05-24

A new short interspersed element (SINE) was isolated from the genome of desert kangaroo rat (Dipodomys deserti) using single-primer PCR. This SINE consists of two monomers: the left monomer (IDL) resembles rodent ID element and other tRNAAla(CGC)-derived SINEs, whereas the right one (Geo) shows no similarity with known SINE sequences. PCR and hybridization analyses demonstrated that IDL-Geo SINE is restricted to the rodent superfamily Geomyoidea (families Geomyidea and Heteromyidea). Isolation and analysis of IDL-Geo from California pocket mouse (Chaetodipus californicus) and Botta's pocket gopher (Thomomys bottae) revealed some species-specific features of this SINE family. The structure and evolution of known dimeric SINEs are discussed.

Hantavirus pulmonary syndrome and rodent reservoirs in the savanna-like biome of Brazil's southeastern region.

Science.gov (United States)

Limongi, J E; Oliveira, R C; Guterres, A; Costa Neto, S F; Fernandes, J; Vicente, L H B; Coelho, M G; Ramos, V N; Ferreira, M S; Bonvicino, C R; D'Andrea, P S; Lemos, E R S

2016-04-01

This paper describes the diversity of rodent fauna in an area endemic for hantavirus cardiopulmonary syndrome (HCPS) in Brazil, the population dynamics and the relationship of rodents with hantavirus in the Cerrado (savanna-like) biome. Additionally, an analysis is made of the partial S segment sequences of the hantaviruses obtained from serologically confirmed human HCPS cases and from rodent specimens. Rodents were collected during four campaigns. Human serum samples were collected from suspected cases of HCPS at hospitals in the state of Minas Gerais. The samples antibody-reactive by ELISA were processed by RT-PCR. The PCR product was amplified and sequenced. Hantavirus was detected only in Necromys lasiurus, the wild rodent species most prevalent in the Cerrado biome (min-max: 50-83·7%). All the six human serum samples were hantavirus seropositive and five showed amplified PCR products. The analysis of the nucleotide sequences showed the circulation of a single genotype, the Araraquara hantavirus. The environmental changes that have occurred in the Cerrado biome in recent decades have favoured N. lasiurus in interspecific competition of habitats, thus increasing the risk of contact between humans and rodent species infected with hantavirus. Our data corroborate the definition of N. lasiurus as the main hantavirus reservoir in the Cerrado biome.

Detection and Characterization of Homologues of Human Hepatitis Viruses and Pegiviruses in Rodents and Bats in Vietnam.

Science.gov (United States)

Van Nguyen, Dung; Van Nguyen, Cuong; Bonsall, David; Ngo, Tue Tri; Carrique-Mas, Juan; Pham, Anh Hong; Bryant, Juliet E; Thwaites, Guy; Baker, Stephen; Woolhouse, Mark; Simmonds, Peter

2018-02-28

Rodents and bats are now widely recognised as important sources of zoonotic virus infections in other mammals, including humans. Numerous surveys have expanded our knowledge of diverse viruses in a range of rodent and bat species, including their origins, evolution, and range of hosts. In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus , while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Complete or near-complete genome sequences of HBV, HEV and pegivirus homologues closely resembled those previously reported from rodents and bats. However, complete coding region sequences of the rodent hepacivirus-like viruses substantially diverged from all of the currently classified variants and potentially represent a new species in the Hepacivirus genus. Of the viruses identified, their routes of transmission and potential to establish zoonoses remain to be determined.

Mycobacterial lesions in fish, amphibians, reptiles, rodents, lagomorphs, and ferrets with reference to animal models.

Science.gov (United States)

Reavill, Drury R; Schmidt, Robert E

2012-01-01

Mycobacteriosis is a serious disease across many animal species. Approximately more than 120 species are currently recognized in the genus Mycobacterium. This article describes the zoonotic potential of mycobacteria and mycobacteriosis in fish, amphibians, rodents, rabbits, and ferrets. It considers clinical signs; histology; molecular methods of identification, such as polymerase chain reaction and DNA sequencing; routes of infection; and disease progression. Studying the disease in animals may aid in understanding the pathogenesis of mycobacterial infections in humans and identify better therapy and preventative options such as vaccines.

Models of breast cancer: quo vadis, animal modeling?

International Nuclear Information System (INIS)

Wagner, Kay-Uwe

2004-01-01

Rodent models for breast cancer have for many decades provided unparalleled insights into cellular and molecular aspects of neoplastic transformation and tumorigenesis. Despite recent improvements in the fidelity of genetically engineered mice, rodent models are still being criticized by many colleagues for not being 'authentic' enough to the human disease. Motives for this criticism are manifold and range from a very general antipathy against the rodent model system to well-founded arguments that highlight physiological variations between species. Newly proposed differences in genetic pathways that cause cancer in humans and mice invigorated the ongoing discussion about the legitimacy of the murine system to model the human disease. The present commentary intends to stimulate a debate on this subject by providing the background about new developments in animal modeling, by disputing suggested limitations of genetically engineered mice, and by discussing improvements but also ambiguous expectations on the authenticity of xenograft models to faithfully mimic the human disease

Rough-legged buzzards, Arctic foxes and red foxes in a tundra ecosystem without rodents.

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Ivan Pokrovsky

Full Text Available Small rodents with multi-annual population cycles strongly influence the dynamics of food webs, and in particular predator-prey interactions, across most of the tundra biome. Rodents are however absent from some arctic islands, and studies on performance of arctic predators under such circumstances may be very instructive since rodent cycles have been predicted to collapse in a warming Arctic. Here we document for the first time how three normally rodent-dependent predator species-rough-legged buzzard, arctic fox and red fox - perform in a low-arctic ecosystem with no rodents. During six years (in 2006-2008 and 2011-2013 we studied diet and breeding performance of these predators in the rodent-free Kolguev Island in Arctic Russia. The rough-legged buzzards, previously known to be a small rodent specialist, have only during the last two decades become established on Kolguev Island. The buzzards successfully breed on the island at stable low density, but with high productivity based on goslings and willow ptarmigan as their main prey - altogether representing a novel ecological situation for this species. Breeding density of arctic fox varied from year to year, but with stable productivity based on mainly geese as prey. The density dynamic of the arctic fox appeared to be correlated with the date of spring arrival of the geese. Red foxes breed regularly on the island but in very low numbers that appear to have been unchanged over a long period - a situation that resemble what has been recently documented from Arctic America. Our study suggests that the three predators found breeding on Kolguev Island possess capacities for shifting to changing circumstances in low-arctic ecosystem as long as other small - medium sized terrestrial herbivores are present in good numbers.

A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special?

Science.gov (United States)

Luis, Angela D.; Hayman, David T. S.; O'Shea, Thomas J.; Cryan, Paul M.; Gilbert, Amy T.; Pulliam, Juliet R. C.; Mills, James N.; Timonin, Mary E.; Willis, Craig K. R.; Cunningham, Andrew A.; Fooks, Anthony R.; Rupprecht, Charles E.; Wood, James L. N.; Webb, Colleen T.

2013-01-01

Bats are the natural reservoirs of a number of high-impact viral zoonoses. We present a quantitative analysis to address the hypothesis that bats are unique in their propensity to host zoonotic viruses based on a comparison with rodents, another important host order. We found that bats indeed host more zoonotic viruses per species than rodents, and we identified life-history and ecological factors that promote zoonotic viral richness. More zoonotic viruses are hosted by species whose distributions overlap with a greater number of other species in the same taxonomic order (sympatry). Specifically in bats, there was evidence for increased zoonotic viral richness in species with smaller litters (one young), greater longevity and more litters per year. Furthermore, our results point to a new hypothesis to explain in part why bats host more zoonotic viruses per species: the stronger effect of sympatry in bats and more viruses shared between bat species suggests that interspecific transmission is more prevalent among bats than among rodents. Although bats host more zoonotic viruses per species, the total number of zoonotic viruses identified in bats (61) was lower than in rodents (68), a result of there being approximately twice the number of rodent species as bat species. Therefore, rodents should still be a serious concern as reservoirs of emerging viruses. These findings shed light on disease emergence and perpetuation mechanisms and may help lead to a predictive framework for identifying future emerging infectious virus reservoirs. PMID:23378666

A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special?

Science.gov (United States)

Luis, Angela D.; Hayman, David T.S.; O'Shea, Thomas J.; Cryan, Paul M.; Gilbert, Amy T.; Pulliam, Juliet R.C.; Mills, James N.; Timonin, Mary E.; Willis, Craig K.R.; Cunningham, Andrew A.; Fooks, Anthony R.; Rupprecht, Charles E.; Wood, James L.N.; Webb, Colleen T.

2013-01-01

Bats are the natural reservoirs of a number of high-impact viral zoonoses. We present a quantitative analysis to address the hypothesis that bats are unique in their propensity to host zoonotic viruses based on a comparison with rodents, another important host order. We found that bats indeed host more zoonotic viruses per species than rodents, and we identified life-history and ecological factors that promote zoonotic viral richness. More zoonotic viruses are hosted by species whose distributions overlap with a greater number of other species in the same taxonomic order (sympatry). Specifically in bats, there was evidence for increased zoonotic viral richness in species with smaller litters (one young), greater longevity and more litters per year. Furthermore, our results point to a new hypothesis to explain in part why bats host more zoonotic viruses per species: the stronger effect of sympatry in bats and more viruses shared between bat species suggests that interspecific transmission is more prevalent among bats than among rodents. Although bats host more zoonotic viruses per species, the total number of zoonotic viruses identified in bats (61) was lower than in rodents (68), a result of there being approximately twice the number of rodent species as bat species. Therefore, rodents should still be a serious concern as reservoirs of emerging viruses. These findings shed light on disease emergence and perpetuation mechanisms and may help lead to a predictive framework for identifying future emerging infectious virus reservoirs.

SHP-1 activation inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in a rodent model of insulin resistance and diabetes

DEFF Research Database (Denmark)

Qi, Weier; Li, Qian; Liew, Chong Wee

2017-01-01

. However, the role of SHP-1 in intimal hyperplasia and restenosis has not been clarified in insulin resistance and diabetes. METHODS: We used a femoral artery wire injury mouse model, rodent models with insulin resistance and diabetes, and patients with type 2 diabetes. Further, we modulated SHP-1...... expression using a transgenic mouse that overexpresses SHP-1 in VSMCs (Shp-1-Tg). SHP-1 agonists were also employed to study the molecular mechanisms underlying the regulation of SHP-1 by oxidised lipids. RESULTS: Mice fed a high-fat diet (HFD) exhibited increased femoral artery intimal hyperplasia...... and decreased arterial SHP-1 expression compared with mice fed a regular diet. Arterial SHP-1 expression was also decreased in Zucker fatty rats, Zucker diabetic fatty rats and in patients with type 2 diabetes. In primary cultured VSMCs, oxidised LDL suppressed SHP-1 expression by activating Mek-1 (also known...

Development of a murine model of acute radiation encephalopathy

International Nuclear Information System (INIS)

Xing Yigang; Tang Yamei; Liu Jun; Sun Ying

2003-01-01

Objective: To develop a murine model of acute radiation encephalopathy. Methods: A total of 40 rats were subjected to local γ-irradiation to the brain with the dosage of 7 Gy/d for 6 consecutive days. The amount of food intake, hairs and skin of irradiated field, body weight, general activities, CNS symptoms and signs were examined and recorded after irradiation. On day 3, 7, 14 and 30, the brain tissue was removed to observe histopathologic changes. Results: During the first two days after irradiation, the irradiated rats were agitated, and the amount of food intake decreased from day 2 onwards. No serious skin reaction to irradiation was observed. Survived rats had normal activities without any abnormal nervous signs. Histopathologic changes showed slight neuronal degeneration, smaller cell body, red-colored cytoplasm, disappearance of Nissl body, vacuolation, typical cell shrinkage, chromatin condensation and nuclear divergence. On the 14th and 30th days, hypochromatism, loose and reticular necrotic foci were found in some samples. Conclusion: The murine model of acute radiation encephalopathy is useful and practical in radiobiological studies

Hepatozoon spp. infections in wild rodents in an area of endemic canine hepatozoonosis in southeastern Brazil.

Science.gov (United States)

Demoner, Larissa de Castro; Magro, Natalia Mizuhira; da Silva, Maria Regina Lucas; de Paula Antunes, João Marcelo Azevedo; Calabuig, Cecilia Irene Pérez; O'Dwyer, Lucia Helena

2016-07-01

Hepatozoon canis is a tick-borne parasite that occurs worldwide. In rural areas of Brazil, H. canis vectors remain unknown, which has led to speculation about alternative routes of transmission. Small rodents can play a role in the transmission (via predation) of Hepatozoon americanum, which led us to question whether predation might be an alternative mode of transmission for H. canis. Thus, this study investigated whether Hepatozoon spp. are present in wild small rodents in forest fragments that surround rural areas in Botucatu County, São Paulo, Brazil, where canine hepatozoonosis is endemic. The study included blood samples from 158 dogs, which were screened by microscopy and molecular analysis. Blood samples and tissues from 67 rodents were obtained for histopathology and molecular detection. The prevalence of H. canis was high (66.45%) in dogs from rural areas of Botucatu, São Paulo, Brazil. The molecular analysis showed that wild rodent species in Brazil were infected with Hepatozoon spp. other than H. canis. Therefore, although the hypothesis that sylvatic rodents act as reservoirs for H. canis was not supported, the presence of monozoic cysts in the rodents suggests that, in addition to intermediate hosts, wild small rodents in Brazil might act as paratenic hosts of Hepatozoon spp. because they harbor infective stages for intermediate host predators. Copyright © 2016 Elsevier GmbH. All rights reserved.

Verification of natural infection of peridomestic rodents by PCV2 on commercial swine farms.

Science.gov (United States)

Pinheiro, Albanno Leonard Braz Campos; Bulos, Luiz Henrique Silva; Onofre, Thiago Souza; de Paula Gabardo, Michelle; de Carvalho, Otávio Valério; Fausto, Mariana Costa; Guedes, Roberto Maurício Carvalho; de Almeida, Márcia Rogéria; Silva Júnior, Abelardo

2013-06-01

The porcine circovirus-2 (PCV2) is the main agent responsible for porcine circovirus associated diseases (PCVAD). Few studies have been done regarding PCV2 infection in other species. The purpose of this study was to investigate the occurrence of PCV2 infection in the peridomestic rodent species Mus musculus and Rattus rattus on commercial pig farms in Brazil. Immunohistochemistry assay demonstrated PCV2 in the spleen, lung and kidney. Viral DNA was detected in tissues by nested PCR assay. Partial sequences of PCV2 genomes detected in the rodents had strong identity with gene sequences of PCV2 isolates from pigs. These results show that the studied peridomestic rodent species can be naturally infected by PCV2. However, further studies are needed to confirm PCV2 transmission from rodents to pigs. Copyright © 2012 Elsevier Ltd. All rights reserved.

The expression of plasticity-related genes in an acute model of stress is modulated by chronic desipramine in a time-dependent manner within medial prefrontal cortex.

Science.gov (United States)

Nava, Nicoletta; Treccani, Giulia; Müller, Heidi Kaastrup; Popoli, Maurizio; Wegener, Gregers; Elfving, Betina

2017-01-01

It is well established that stress plays a major role in the pathogenesis of neuropsychiatric diseases. Stress-induced alteration of synaptic plasticity has been hypothesized to underlie the morphological changes observed by neuroimaging in psychiatric patients in key regions such as hippocampus and prefrontal cortex (PFC). We have recently shown that a single acute stress exposure produces significant short-term alterations of structural plasticity within medial PFC. These alterations were partially prevented by previous treatment with chronic desipramine (DMI). In the present study we evaluated the effects of acute Foot-shock (FS)-stress and pre-treatment with the traditional antidepressant DMI on the gene expression of key regulators of synaptic plasticity and structure. Expression of Homer, Shank, Spinophilin, Densin-180, and the small RhoGTPase related gene Rac1 and downstream target genes, Limk1, Cofilin1 and Rock1 were investigated 1 day (1d), 7 d and 14d after FS-stress exposure. We found that DMI specifically increases the short-term expression of Spinophilin, as well as Homer and Shank family genes, and that both acute stress and DMI exert significant long-term effects on mRNA levels of genes involved in spine plasticity. These findings support the knowledge that acute FS stress and antidepressant treatment induce both rapid and sustained time-dependent alterations in structural components of synaptic plasticity in rodent medial PFC. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Interaction of genotype and environment: Effect of strain and housing condition on cognitive behaviour in rodent models of schizophrenia

Directory of Open Access Journals (Sweden)

Karly M. Turner

2013-07-01

Full Text Available Schizophrenia is associated with many genetic and environmental risk factors and there is growing evidence that the interactions between genetic and environmental ‘hits’ are critical for disease onset. Animal models of schizophrenia have traditionally used specific strain and housing conditions to test potential risk factors. As the field moves towards testing gene (G x environment (E interactions the impact of these choices should be considered. Given the surge of research focused on cognitive deficits, we have examined studies of cognition in rodents from the perspective of GxE interactions, in which strain or housing manipulations have been varied. Behaviour is clearly altered by these factors, yet few animal models of schizophrenia have investigated cognitive deficits using different strain and housing conditions. It is important to recognise the large variation in behaviour observed when using different strain and housing combinations because GxE interactions may mask or exacerbate cognitive outcomes. Further consideration will improve our understanding of GxE interactions and the underlying neurobiology of cognitive impairments in neuropsychiatric disorders.

Taxonomical studies of ticks infesting wild rodents from Asir Province in Saudi Arabia.

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Al-Mohammed, Hamdan I

2008-04-01

Ticks infesting rodents in Asir Province, which is about 3000 meter above sea level, were surveyed in Wadi Dalaghan and Wadi Bin Hachbal. They were examined from September to December 2006, where ten local life baited traps were distributed for 3 days each month. The rodents were Acomys c. dimitatus (20), Meriones rex (19) & one Gerbillus cheesmani. Fifty three nymphs were dropped off from the rodents in the laboratory 3 to 12 days post-trapping. Forty eight nymphs were reared to adults for identification and 5 ones died. The reared ticks were Rhipicephalus turanicus and R. sanguineus. The medical and veterinary importance was discussed.

Acute metabolic decompensation due to influenza in a mouse model of ornithine transcarbamylase deficiency

Directory of Open Access Journals (Sweden)

Peter J. McGuire

2014-02-01

Full Text Available The urea cycle functions to incorporate ammonia, generated by normal metabolism, into urea. Urea cycle disorders (UCDs are caused by loss of function in any of the enzymes responsible for ureagenesis, and are characterized by life-threatening episodes of acute metabolic decompensation with hyperammonemia (HA. A prospective analysis of interim HA events in a cohort of individuals with ornithine transcarbamylase (OTC deficiency, the most common UCD, revealed that intercurrent infection was the most common precipitant of acute HA and was associated with markers of increased morbidity when compared with other precipitants. To further understand these clinical observations, we developed a model system of metabolic decompensation with HA triggered by viral infection (PR8 influenza using spf-ash mice, a model of OTC deficiency. Both wild-type (WT and spf-ash mice displayed similar cytokine profiles and lung viral titers in response to PR8 influenza infection. During infection, spf-ash mice displayed an increase in liver transaminases, suggesting a hepatic sensitivity to the inflammatory response and an altered hepatic immune response. Despite having no visible pathological changes by histology, WT and spf-ash mice had reduced CPS1 and OTC enzyme activities, and, unlike WT, spf-ash mice failed to increase ureagenesis. Depression of urea cycle function was seen in liver amino acid analysis, with reductions seen in aspartate, ornithine and arginine during infection. In conclusion, we developed a model system of acute metabolic decompensation due to infection in a mouse model of a UCD. In addition, we have identified metabolic perturbations during infection in the spf-ash mice, including a reduction of urea cycle intermediates. This model of acute metabolic decompensation with HA due to infection in UCD serves as a platform for exploring biochemical perturbations and the efficacy of treatments, and could be adapted to explore acute decompensation in other

Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury.

Science.gov (United States)

Ritter, Anne C; Wagner, Amy K; Szaflarski, Jerzy P; Brooks, Maria M; Zafonte, Ross D; Pugh, Mary Jo V; Fabio, Anthony; Hammond, Flora M; Dreer, Laura E; Bushnik, Tamara; Walker, William C; Brown, Allen W; Johnson-Greene, Doug; Shea, Timothy; Krellman, Jason W; Rosenthal, Joseph A

2016-09-01

Posttraumatic seizures (PTS) are well-recognized acute and chronic complications of traumatic brain injury (TBI). Risk factors have been identified, but considerable variability in who develops PTS remains. Existing PTS prognostic models are not widely adopted for clinical use and do not reflect current trends in injury, diagnosis, or care. We aimed to develop and internally validate preliminary prognostic regression models to predict PTS during acute care hospitalization, and at year 1 and year 2 postinjury. Prognostic models predicting PTS during acute care hospitalization and year 1 and year 2 post-injury were developed using a recent (2011-2014) cohort from the TBI Model Systems National Database. Potential PTS predictors were selected based on previous literature and biologic plausibility. Bivariable logistic regression identified variables with a p-value models. Multivariable logistic regression modeling with backward-stepwise elimination was used to determine reduced prognostic models and to internally validate using 1,000 bootstrap samples. Fit statistics were calculated, correcting for overfitting (optimism). The prognostic models identified sex, craniotomy, contusion load, and pre-injury limitation in learning/remembering/concentrating as significant PTS predictors during acute hospitalization. Significant predictors of PTS at year 1 were subdural hematoma (SDH), contusion load, craniotomy, craniectomy, seizure during acute hospitalization, duration of posttraumatic amnesia, preinjury mental health treatment/psychiatric hospitalization, and preinjury incarceration. Year 2 significant predictors were similar to those of year 1: SDH, intraparenchymal fragment, craniotomy, craniectomy, seizure during acute hospitalization, and preinjury incarceration. Corrected concordance (C) statistics were 0.599, 0.747, and 0.716 for acute hospitalization, year 1, and year 2 models, respectively. The prognostic model for PTS during acute hospitalization did not

A glimpse on the pattern of rodent diversification

DEFF Research Database (Denmark)

Fabre, Pierre-Henri Fréderic; Hautier, Lionel; Dimitrov, Dimitar Stefanov

2012-01-01

BACKGROUND:Development of phylogenetic methods that do not rely on fossils for the study of evolutionary processes through time have revolutionized the field of evolutionary biology and resulted in an unprecedented expansion of our knowledge about the tree of life. These methods have helped to shed...... molecular works. A relaxed molecular clock dating approach provided a time framework for speciation events. We found that the Myomorpha clade shows a greater degree of variation in diversification rates than Sciuroidea, Caviomorpha, Castorimorpha and Anomaluromorpha. We identified a number of shifts...... imbalances and the time line we discuss the potential role of different diversification factors that might have shaped the rodents radiation. CONCLUSIONS:The present glimpse on the diversification pattern of rodents can be used for further comparative meta-analyses. Muroid lineages have a greater degree...

Development of Toxicological Risk Assessment Models for Acute and Chronic Exposure to Pollutants

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Elke S. Reichwaldt

2016-08-01

Full Text Available Alert level frameworks advise agencies on a sequence of monitoring and management actions, and are implemented so as to reduce the risk of the public coming into contact with hazardous substances. Their effectiveness relies on the detection of the hazard, but with many systems not receiving any regular monitoring, pollution events often go undetected. We developed toxicological risk assessment models for acute and chronic exposure to pollutants that incorporate the probabilities that the public will come into contact with undetected pollution events, to identify the level of risk a system poses in regards to the pollutant. As a proof of concept, we successfully demonstrated that the models could be applied to determine probabilities of acute and chronic illness types related to recreational activities in waterbodies containing cyanotoxins. Using the acute model, we identified lakes that present a ‘high’ risk to develop Day Away From Work illness, and lakes that present a ‘low’ or ‘medium’ risk to develop First Aid Cases when used for swimming. The developed risk models succeeded in categorising lakes according to their risk level to the public in an objective way. Modelling by how much the probability of public exposure has to decrease to lower the risks to acceptable levels will enable authorities to identify suitable control measures and monitoring strategies. We suggest broadening the application of these models to other contaminants.

Soetomo score: score model in early identification of acute haemorrhagic stroke

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Moh Hasan Machfoed

2016-06-01

Full Text Available Aim of the study: On financial or facility constraints of brain imaging, score model is used to predict the occurrence of acute haemorrhagic stroke. Accordingly, this study attempts to develop a new score model, called Soetomo score. Material and methods: The researchers performed a cross-sectional study of 176 acute stroke patients with onset of ≤24 hours who visited emergency unit of Dr. Soetomo Hospital from July 14th to December 14th, 2014. The diagnosis of haemorrhagic stroke was confirmed by head computed tomography scan. There were seven predictors of haemorrhagic stroke which were analysed by using bivariate and multivariate analyses. Furthermore, a multiple discriminant analysis resulted in an equation of Soetomo score model. The receiver operating characteristic procedure resulted in the values of area under curve and intersection point identifying haemorrhagic stroke. Afterward, the diagnostic test value was determined. Results: The equation of Soetomo score model was (3 × loss of consciousness + (3.5 × headache + (4 × vomiting − 4.5. Area under curve value of this score was 88.5% (95% confidence interval = 83.3–93.7%. In the Soetomo score model value of ≥−0.75, the score reached the sensitivity of 82.9%, specificity of 83%, positive predictive value of 78.8%, negative predictive value of 86.5%, positive likelihood ratio of 4.88, negative likelihood ratio of 0.21, false negative of 17.1%, false positive of 17%, and accuracy of 83%. Conclusions: The Soetomo score model value of ≥−0.75 can identify acute haemorrhagic stroke properly on the financial or facility constrains of brain imaging.

The Upper Miocene rodents from the Pezinok in the Danube Basin, Slovakia

OpenAIRE

Peter Joniak

2016-01-01

Rodent assemblages are described from two sampled sites at the Pezinok clay pit in the Danube Basin. Although these assemblages contain material poor in specimens, the following eleven rodent taxa are distinguished and described: Progonomys hispanicus, Kowalskia sp., Microtocricetus molassicus, Anomalomys gaillardi, Graphiurops austriacus, Paraglirulus sp., Eomyops catalaunicus, Keramidomys sp., Spermophilinus sp., Albanensia sp. and Euroxenomys minutum. The co-occurrence of very primitive Pr...

Endotoxin, coliform, and dust levels in various types of rodent bedding.

Science.gov (United States)

Whiteside, Tanya E; Thigpen, Julius E; Kissling, Grace E; Grant, Mary G; Forsythe, Diane

2010-03-01

Endotoxins in grain dust, household dust, and animal bedding may induce respiratory symptoms in rodents and humans. We assayed the endotoxin, coliform, and dust levels in 20 types of rodent bedding. Endotoxin concentrations were measured by using a commercial test kit, coliform counts were determined by using conventional microbiologic procedures, and dust content was evaluated by using a rotating-tapping shaker. Paper bedding types contained significantly less endotoxin than did other bedding types; the highest levels of endotoxin were detected in hardwood and corncob beddings. The range of endotoxin content for each bedding type was: corncob bedding, 1913 to 4504 endotoxin units per gram (EU/g); hardwood bedding, 3121 to 5401 EU/g; corncob-paper mixed bedding, 1586 to 2416 EU/g; and paper bedding, less than 5 to 105 EU/g. Coliform counts varied from less than 10 to 7591 cfu/g in corncob beddings, 90 to 4010 cfu/g in corncob-paper mixed beddings, less than 10 to 137 cfu/g in hardwood beddings, and less than 10 cfu/g in paper beddings. Average dust content was less than 0.15% in all commercial bedding types. We conclude that paper bedding is the optimal bedding type for conducting LPS inhalation studies and that rodent bedding containing high levels of endotoxin may alter the results of respiratory and immunologic studies in rodents.

Identification of rodent homologs of hepatitis C virus and pegiviruses

DEFF Research Database (Denmark)

Kapoor, Amit; Simmonds, Peter; Scheel, Troels K H

2013-01-01

UNLABELLED: Hepatitis C virus (HCV) and human pegivirus (HPgV or GB virus C) are globally distributed and infect 2 to 5% of the human population. The lack of tractable-animal models for these viruses, in particular for HCV, has hampered the study of infection, transmission, virulence, immunity...... into the origins of human infections and enhances our ability to study their pathogenesis and explore preventive and therapeutic interventions. Horses are the only reported host of nonprimate homologs of hepatitis C virus (HCV). Here, we report the discovery of HCV-like viruses in wild rodents. The majority of HCV...... of small-animal models for HCV, the most common infectious cause of liver failure and hepatocellular carcinoma after hepatitis B virus, and help to explore the health relevance of the highly prevalent human pegiviruses....

Rodent malaria parasites : genome organization & comparative genomics

NARCIS (Netherlands)

Kooij, Taco W.A.

2006-01-01

The aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs and the human malaria parasite P. falciparum. The release of the complete genome sequence of P.

Food habits of rodents inhabiting arid and semi-arid ecosystems of central New Mexico

Science.gov (United States)

Hope, Andrew G.; Parmenter, Robert R.

2007-01-01

In this study, we describe seasonal dietary composition for 15 species of rodents collected in all major habitats on the Sevilleta National Wildlife Refuge (Socorro County) in central New Mexico. A comprehensive literature review of food habits for these species from throughout their distribution also is provided. We collected rodents in the field during winter, spring and late summer in 1998 from six communities: riparian cottonwood forest; piñon-juniper woodland; juniper-oak savanna; mesquite savanna; short-grass steppe; and Chihuahuan Desert scrubland. Rodents included Spermophilus spilosoma (Spotted Ground Squirrel), Perognathus flavescens (Plains Pocket Mouse), Perognathus flavus (Silky Pocket Mouse), Dipodomys merriami (Merriam’s Kangaroo Rat), Dipodomys ordii (Ord’s Kangaroo Rat), Dipodomys spectabilis (Banner-tailed Kangaroo Rat), Reithrodontomys megalotis (Western Harvest Mouse), Peromyscus boylii (Brush Mouse), Peromyscus eremicus (Cactus Mouse), Peromyscus leucopus (White-footed Mouse), Peromyscus truei (Piñon Mouse), Onychomys arenicola (Mearn’s Grasshopper Mouse), Onychomys leucogaster (Northern Grasshopper Mouse), Neotoma albigula/leucodon (White-throated Woodrats), and Neotoma micropus (Southern Plains Woodrat). We collected stomach contents of all species, and cheek-pouch contents of heteromyids, and quantified them in the laboratory. We determined seasonal diets in each habitat by calculating mean percentage volumes of seeds, arthropods and green vegetation (plant leaves and stems) for each species of rodent. Seeds consumed by each rodent were identified to genus, and often species, and quantified by frequency counts. Comparisons of diets between and among species of rodents, seasons, and ecosystems were also examined. We provide an appendix of all plant taxa documented.

[Population change of farmland rodent and the influences of climate and cultivation factors in Fengxian District of Shanghai, China].

Science.gov (United States)

Fei, Lei; Wang, Zu-guo; Yao, Yao; Xu, Xiang-ming; Gu, Pin-qiang

2015-02-01

We analyzed the changes of rodent population from 1988 to 2013 in Fengxian District, Shanghai, and discussed the relevance of rodent population dynamics and climate, and ecological factors. Results showed that the average rat density was 1.3% from 1988 to 2013, and the dominant species was Apodemus agrarius. There was little change of density between years. The average composition ratio was 97.5%. The peak of rodent density appeared from February to May, highest in March. Average density and peak decreased obviously year after year. Numbers of adult rodents of 1st group were positively correlated, while that of adult rodents of 2nd group and elderly group negatively correlated with years. Rat age presented a shortened trend annually. Rodent density and temperature factors were negatively correlated except in January. Extreme warmth in February had a lagged, positive effect on the rat density. Precipitation factors had no significant correlation with the density of rodents. Relative humidity was positively correlated with the density, mostly. Planting structure adjustment and reduction of planting acreage were significantly correlated with the reduction of rodent density. Increased deratization rate was also correlated with the reduction.

In vivo imaging of neuro-inflammation in the rodent brain with [11C]SSR180575, a novel indoleacetamide radioligand of the translocator protein (18 kDa)

International Nuclear Information System (INIS)

Chauveau, F.; Boutin, H.; Van Camp, N.; Thominiaux, C.; Dolle, F.; Tavitian, B.; Chauveau, F.; Boutin, H.; Van Camp, N.; Tavitian, B.; Hantraye, P.; Rivron, L.; Marguet, F.; Castel, M.N.; Rooney, T.; Benavides, J.; Chauveau, F.; Boutin, H.

2011-01-01

Purpose Neuro-inflammation is involved in neurological disorders through the activation of micro-glial cells. Imaging of neuro-inflammation with radioligands for the translocator protein (18 kDa) (TSPO) could prove to be an attractive bio-marker for disease diagnosis and therapeutic evaluation. The indoleacetamide-derived 7-chloro-N, N, 5- trimethyl-4-oxo-3-phenyl-3, 5-dihydro-4H-pyridazino[4, 5-b] indole-1-acetamide, SSR180575, is a selective high-affinity TSPO ligand in human and rodents with neuro-protective effects. Methods Here we report the radiolabelling of SSR180575 with 11 C and in vitro and in vivo imaging in an acute model of neuro-inflammation in rats. Results The image contrast and the binding of [ 11 C] SSR180575 are higher than that obtained with the isoquinoline- based TSPO radioligand, [ 11 C]PK11195. Competition studies demonstrate that [ 11 C]SSR180575 has high specific binding for the TSPO. Conclusion [ 11 C]SSR180575 is the first PET radioligand for the TSPO based on an indoleacetamide scaffold designed for imaging neuro-inflammation in animal models and in the clinic. (authors)

Sex differences in the acute locomotor response to methamphetamine in BALB/c mice.

Science.gov (United States)

Ohia-Nwoko, Odochi; Haile, Colin N; Kosten, Therese A

2017-06-01

Women use methamphetamine more frequently than men and are more vulnerable to its negative psychological effects. Rodent models have been an essential tool for evaluating the sex-dependent effects of psychostimulants; however, evidence of sex differences in the behavioral responses to methamphetamine in mice is lacking. In the present study, we investigated acute methamphetamine-induced (1mg/kg and 4mg/kg) locomotor activation in female and male BALB/c mice. We also evaluated whether basal locomotor activity was associated with the methamphetamine-induced locomotor response. The results indicated that female BALB/c mice displayed enhanced methamphetamine-induced locomotor activity compared to males, while basal locomotor activity was positively correlated with methamphetamine-induced activity in males, but not females. This study is the first to show sex-dependent locomotor effects of methamphetamine in BALB/c mice. Our observations emphasize the importance of considering sex when assessing behavioral responses to methamphetamine. Copyright © 2017 Elsevier B.V. All rights reserved.

Segmentation of rodent whole-body dynamic PET images: an unsupervised method based on voxel dynamics

DEFF Research Database (Denmark)

Maroy, Renaud; Boisgard, Raphaël; Comtat, Claude

2008-01-01

Positron emission tomography (PET) is a useful tool for pharmacokinetics studies in rodents during the preclinical phase of drug and tracer development. However, rodent organs are small as compared to the scanner's intrinsic resolution and are affected by physiological movements. We present a new...... method for the segmentation of rodent whole-body PET images that takes these two difficulties into account by estimating the pharmacokinetics far from organ borders. The segmentation method proved efficient on whole-body numerical rat phantom simulations, including 3-14 organs, together...

Standardization of formulations for the acute amino acid depletion and loading tests.

Science.gov (United States)

Badawy, Abdulla A-B; Dougherty, Donald M

2015-04-01

The acute tryptophan depletion and loading and the acute tyrosine plus phenylalanine depletion tests are powerful tools for studying the roles of cerebral monoamines in behaviour and symptoms related to various disorders. The tests use either amino acid mixtures or proteins. Current amino acid mixtures lack specificity in humans, but not in rodents, because of the faster disposal of branched-chain amino acids (BCAAs) by the latter. The high content of BCAA (30-60%) is responsible for the poor specificity in humans and we recommend, in a 50g dose, a control formulation with a lowered BCAA content (18%) as a common control for the above tests. With protein-based formulations, α-lactalbumin is specific for acute tryptophan loading, whereas gelatine is only partially effective for acute tryptophan depletion. We recommend the use of the whey protein fraction glycomacropeptide as an alternative protein. Its BCAA content is ideal for specificity and the absence of tryptophan, tyrosine and phenylalanine render it suitable as a template for seven formulations (separate and combined depletion or loading and a truly balanced control). We invite the research community to participate in standardization of the depletion and loading methodologies by using our recommended amino acid formulation and developing those based on glycomacropeptide. © The Author(s) 2015.

Phenotyping animal models of diabetic neuropathy

DEFF Research Database (Denmark)

Biessels, G J; Bril, V; Calcutt, N A

2014-01-01

NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy...... with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence...

Toxoplasma gondii antibodies in wild rodents and marsupials from the Atlantic Forest, state of São Paulo, Brazil

Directory of Open Access Journals (Sweden)

Solange Maria Gennari

Full Text Available Toxoplasma gondii is a protozoan parasite that infects a large spectrum of warm-blooded animals, including humans. Small rodents and marsupials play an important role in the epidemiology of T. gondii because they are sources of infection for domestic and feral cats. Serum samples from 151 rodents and 48 marsupials, captured in the Atlantic Forest, São Paulo State, southeastern Brazil, were analyzed for the presence of T. gondii antibodies. Antibodies detected by the modified agglutination test (MAT ≥ 25 were found in 8.6% (13/151 of the rodents and 10.4% (5/48 of the marsupials, with titers ranging from 25 to 6400 and from 25 to 3200, respectively for the rodents and marsupials. Three of the eight species of rodents (Akodon spp., Oligoryzomys nigripesand Rattus norvegicus, and one from the four marsupial species (Didelphis aurita presented positive animals. T. gondii was described for the first time in the rodent Oligoryzomys nigripes.

Dietary restriction of rodents decreases aging rate without affecting initial mortality rate -- a meta-analysis.

Science.gov (United States)

Simons, Mirre J P; Koch, Wouter; Verhulst, Simon

2013-06-01

Dietary restriction (DR) extends lifespan in multiple species from various taxa. This effect can arise via two distinct but not mutually exclusive ways: a change in aging rate and/or vulnerability to the aging process (i.e. initial mortality rate). When DR affects vulnerability, this lowers mortality instantly, whereas a change in aging rate will gradually lower mortality risk over time. Unraveling how DR extends lifespan is of interest because it may guide toward understanding the mechanism(s) mediating lifespan extension and also has practical implications for the application of DR. We reanalyzed published survival data from 82 pairs of survival curves from DR experiments in rats and mice by fitting Gompertz and also Gompertz-Makeham models. The addition of the Makeham parameter has been reported to improve the estimation of Gompertz parameters. Both models separate initial mortality rate (vulnerability) from an age-dependent increase in mortality (aging rate). We subjected the obtained Gompertz parameters to a meta-analysis. We find that DR reduced aging rate without affecting vulnerability. The latter contrasts with the conclusion of a recent analysis of a largely overlapping data set, and we show how the earlier finding is due to a statistical artifact. Our analysis indicates that the biology underlying the life-extending effect of DR in rodents likely involves attenuated accumulation of damage, which contrasts with the acute effect of DR on mortality reported for Drosophila. Moreover, our findings show that the often-reported correlation between aging rate and vulnerability does not constrain changing aging rate without affecting vulnerability simultaneously. © 2013 John Wiley & Sons Ltd and the Anatomical Society.

Latent Growth Modeling of nursing care dependency of acute neurological inpatients.

Science.gov (United States)

Piredda, M; Ghezzi, V; De Marinis, M G; Palese, A

2015-01-01

Longitudinal three-time point study, addressing how neurological adult patient care dependency varies from the admission time to the 3rd day of acute hospitalization. Nursing care dependency was measured with the Care Dependency Scale (CDS) and a Latent Growth Modeling approach was used to analyse the CDS trend in 124 neurosurgical and stroke inpatients. Care dependence followed a decreasing linear trend. Results can help nurse-managers planning an appropriate amount of nursing care for acute neurological patients during their initial stage of hospitalization. Further studies are needed aimed at investigating the determinants of nursing care dependence during the entire in-hospital stay.

Object Recognition Memory and the Rodent Hippocampus

Science.gov (United States)

Broadbent, Nicola J.; Gaskin, Stephane; Squire, Larry R.; Clark, Robert E.

2010-01-01

In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR…

Evaluation of molecular brain changes associated with environmental stress in rodent models compared to human major depressive disorder: A proteomic systems approach.

Science.gov (United States)

Cox, David Alan; Gottschalk, Michael Gerd; Stelzhammer, Viktoria; Wesseling, Hendrik; Cooper, Jason David; Bahn, Sabine

2016-11-25

Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue (n = 12) and matched controls (n = 23) were compared with equivalent data from three commonly used preclinical models exposed to environmental stressors (chronic mild stress, prenatal stress and social defeat). Functional pathophysiological features associated with depression-like behaviour were identified in these models through enrichment of protein-protein interaction networks. A cross-species comparison evaluated which model(s) represent human MDD pathology most closely. Seven functional domains associated with MDD and represented across at least two models such as "carbohydrate metabolism and cellular respiration" were identified. Through statistical evaluation using kernel-based machine learning techniques, the social defeat model was found to represent MDD brain changes most closely for four of the seven domains. This is the first study to apply a method for directly evaluating the relevance of the molecular pathology of multiple animal models to human MDD on the functional level. The methodology and findings outlined here could help to overcome translational obstacles of preclinical psychiatric research.