WorldWideScience

Sample records for stroke animal models

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

    Science.gov (United States)

    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.

  2. A novel animal model of dysphagia following stroke.

    Science.gov (United States)

    Sugiyama, Naoto; Nishiyama, Eiji; Nishikawa, Yukitoshi; Sasamura, Takashi; Nakade, Shinji; Okawa, Katsumasa; Nagasawa, Tadashi; Yuki, Akane

    2014-02-01

    Patients who have an ischemic stroke are at high risk of swallowing disorders. Aspiration due to swallowing disorders, specifically delayed trigger of the pharyngeal stage of swallowing, predisposes such patients to pneumonia. In the present study, we evaluated swallowing reflex in a rat model of transient middle cerebral artery occlusion (tMCAO), which is one of the most common experimental animal models of cerebral ischemia, in order to develop a novel animal model of dysphagia following ischemic stroke. A swallowing reflex was elicited by a 10-s infusion of distilled water (DW) to the pharyngolaryngeal region in the tMCAO rat model. Swallowing reflex was estimated using the electromyographic activity of the mylohyoid muscle from 1 to 3 weeks after surgery. Two weeks after tMCAO, the number of swallows significantly decreased and the onset latency of the first swallow was prolonged compared with that of the sham group. The number of swallows in rats significantly increased by infusions of 10 mM citric acid and 0.6 μM capsaicin to the pharyngolaryngeal region compared with the number from infusion of DW. It has been reported that sensory stimulation of the pharyngolaryngeal region with citric acid, capsaicin, and L-menthol ameliorates hypofunction of pharyngeal-stage swallowing in dysphagia patients. Therefore, the tMCAO rat model may show some of the symptoms of pharyngeal-stage swallowing disorders, similar to those in patients with ischemic stroke. This rat tMCAO model has the potential to become a novel animal model of dysphagia following stroke that is useful for development of therapeutic methods and drugs.

  3. Animal models of ischaemic stroke and characterisation of the ischaemic penumbra.

    Science.gov (United States)

    McCabe, Christopher; Arroja, Mariana M; Reid, Emma; Macrae, I Mhairi

    2017-09-18

    Over the past forty years, animal models of focal cerebral ischaemia have allowed us to identify the critical cerebral blood flow thresholds responsible for irreversible cell death, electrical failure, inhibition of protein synthesis, energy depletion and thereby the lifespan of the potentially salvageable penumbra. They have allowed us to understand the intricate biochemical and molecular mechanisms within the 'ischaemic cascade' that initiate cell death in the first minutes, hours and days following stroke. Models of permanent, transient middle cerebral artery occlusion and embolic stroke have been developed each with advantages and limitations when trying to model the complex heterogeneous nature of stroke in humans. Yet despite these advances in understanding the pathophysiological mechanisms of stroke-induced cell death with numerous targets identified and drugs tested, a lack of translation to the clinic has hampered pre-clinical stroke research. With recent positive clinical trials of endovascular thrombectomy in acute ischaemic stroke the stroke community has been reinvigorated, opening up the potential for future translation of adjunctive treatments that can be given alongside thrombectomy/thrombolysis. This review discusses the major animal models of focal cerebral ischaemia highlighting their advantages and limitations. Acute imaging is crucial in longitudinal pre-clinical stroke studies in order to identify the influence of acute therapies on tissue salvage over time. Therefore, the methods of identifying potentially salvageable ischaemic penumbra are discussed. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  4. Animal Models of Focal Cerebral Ischaemia and Haemorrhagic Transformation: Considerations in Experimental Stroke Study Design.

    Science.gov (United States)

    Shearer, Jennifer A; Douglas, Andrew S; Kirby, Brian P; Tatlisumak, Turgut; Doyle, Karen M

    2017-09-05

    Ischaemic stroke is often complicated with haemorrhage within the infarct zone or in a remote location especially when treated with intravenous thrombolysis and/or thrombectomy. While these early recanalisation treatments are highly effective, some of the benefit is lost because of haemorrhagic complications and consequential neurological deterioration of the patients. A number of mechanisms have been described that mediate the haemorrhagic changes and several agents have been tested in experimental models for inhibiting post stroke haemorrhage. Here, we review and discuss the small animal models of focal cerebral ischaemia and post ischaemic stroke haemorrhagic transformation and how these models can best be utilised for developing further insights as well as potential treatment approaches for this serious clinical complication. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Limitations and pitfalls in measurements of right ventricular stroke volume in an animal model of right heart failure

    International Nuclear Information System (INIS)

    Vildbrad, Mads Dam; Andersen, Asger; Andersen, Thomas Krarup; Axelgaard, Sofie; Holmboe, Sarah; Andersen, Stine; Nielsen-Kudsk, Jens Erik; Ringgaard, Steffen

    2015-01-01

    Right heart failure occurs in various heart and pulmonary vascular diseases and may be fatal. We aimed to identify limitations in non-invasive measurements of right ventricular stroke volume in an animal model of right ventricular failure. Data from previous studies randomising rats to pulmonary trunk banding (PTB, n = 33) causing pressure-overload right ventricular failure or sham operation (n = 16) was evaluated retrospectively. We measured right ventricular stroke volume by high frequency echocardiography and magnetic resonance imaging (MRI). We found correlation between right ventricular stroke volume measured by echocardiography and MRI in the sham animals (r = 0.677, p = 0.004) but not in the PTB group. Echocardiography overestimated the stroke volume compared to MRI in both groups. Intra- and inter-observer variation did not explain the difference. Technical, physiological and anatomical issues in the pulmonary artery might explain why echocardiography over-estimates stroke volume. Flow acceleration close to the pulmonary artery banding can cause uncertainties in the PTB model and might explain the lack of correlation. In conclusion, we found a correlation in right ventricular stroke volume measured by echocardiography versus MRI in the sham group but not the PTB group. Echocardiography overestimated right ventricular stroke volume compared to MRI. (paper)

  6. Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model

    Energy Technology Data Exchange (ETDEWEB)

    Vandeputte, Caroline; Casteels, Cindy; Koole, Michel; Gerits, Anneleen [KU Leuven, Division of Nuclear Medicine, Leuven (Belgium); KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); Struys, Tom [Hasselt University, Laboratory of Histology, Biomedical Research Institute, Hasselt (Belgium); KU Leuven, Biomedical NMR Unit, Leuven (Belgium); Veghel, Daisy van; Evens, Nele; Bormans, Guy [KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); KU Leuven, Laboratory of Radiopharmacy, Leuven (Belgium); Dresselaers, Tom; Himmelreich, Uwe [KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); KU Leuven, Biomedical NMR Unit, Leuven (Belgium); Lambrichts, Ivo [Hasselt University, Laboratory of Histology, Biomedical Research Institute, Hasselt (Belgium); Laere, Koen van [KU Leuven, Division of Nuclear Medicine, Leuven (Belgium); KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); UZ Leuven, Division of Nuclear Medicine, Leuven (Belgium)

    2012-11-15

    Recent ex vivo and pharmacological evidence suggests involvement of the endocannabinoid system in the pathophysiology of stroke, but conflicting roles for type 1 and 2 cannabinoid receptors (CB{sub 1} and CB{sub 2}) have been suggested. The purpose of this study was to evaluate CB{sub 1} and CB{sub 2} receptor binding over time in vivo in a rat photothrombotic stroke model using PET. CB{sub 1} and CB{sub 2} microPET imaging was performed at regular time-points up to 2 weeks after stroke using [{sup 18}F]MK-9470 and [{sup 11}C]NE40. Stroke size was measured using MRI at 9.4 T. Ex vivo validation was performed via immunostaining for CB{sub 1} and CB{sub 2}. Immunofluorescent double stainings were also performed with markers for astrocytes (GFAP) and macrophages/microglia (CD68). [{sup 18}F]MK-9470 PET showed a strong increase in CB{sub 1} binding 24 h and 72 h after stroke in the cortex surrounding the lesion, extending to the insular cortex 24 h after surgery. These alterations were consistently confirmed by CB{sub 1} immunohistochemical staining. [{sup 11}C]NE40 did not show any significant differences between stroke and sham-operated animals, although staining for CB{sub 2} revealed minor immunoreactivity at 1 and 2 weeks after stroke in this model. Both CB{sub 1} {sup +} and CB{sub 2} {sup +} cells showed minor immunoreactivity for CD68. Time-dependent and regionally strongly increased CB{sub 1}, but not CB{sub 2}, binding are early consequences of photothrombotic stroke. Pharmacological interventions should primarily aim at CB{sub 1} signalling as the role of CB{sub 2} seems minor in the acute and subacute phases of stroke. (orig.)

  7. Effects of anti-inflammatory treatments on stroke outcome in animal models

    NARCIS (Netherlands)

    Tiebosch, I.A.C.W.

    2012-01-01

    Background: Stroke is a devastating disease with over 5.5 million yearly casualties worldwide. Acute treatment strategies are limited. The acute inflammatory response following stroke has been demonstrated to be detrimental on stroke outcome, for both ischemic and hemorrhagic stroke subtypes.

  8. Animal models

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Krentz, Andrew

    2014-01-01

    In this issue of Cardiovascular Endocrinology, we are proud to present a broad and dedicated spectrum of reviews on animal models in cardiovascular disease. The reviews cover most aspects of animal models in science from basic differences and similarities between small animals and the human...

  9. Wheels, Cranks, and Cams: An Animated Spreadsheet-Based Mathematical Model of a Four-Stroke Engine.

    Science.gov (United States)

    Callender, J. T.; Jackson, R.

    1998-01-01

    Analyzes the mathematics of rotational and translational motion and how one can influence the other in the context of cams and cranks. Describes how the individual components can be brought together to simulate a four-stroke engine and how the engine animates again using the same simple macro. (Author/ASK)

  10. Permanent flame-blunted monofilament of middle cerebral artery occlusion technique for ischemia stroke induction in animal models

    Directory of Open Access Journals (Sweden)

    Yetty Ramli

    2017-11-01

    Full Text Available Background: Rat is the most frequently used animal for ischemic stroke studies. Recently, middle cerebral artery occlusion (MCAO by introducing various types of surgical monofilament intraluminally has been widely used, with their advantages and disadvantages. For permanent occlusion, problems with mortality in rats are higher than transient. In this study, we used permanent occlusion using modified monofilament by flaming on its tip which may reduce mortality rate, so that chronic phase of stroke can be learned extensively.Methods: Three male Sprague-Dawley rats underwent permanent MCAO. The flame-blunted monofilament was introduced through common carotid artery. Hematoxylin eosin histopathology confirmation and functional assessment post-stroke induction were then evaluated.Results: Evaluation was conducted on 3 rats in different time post-stroke induction (48 hours, 72 hours, and 3 weeks. Using histopathological examination, the infarction was proved in all 3 rats showing red neurons, perivascular edema and neutrophil spongiosis, in infarct and peri-infarct area. The changes in histopathology showed spongiosis were more dominant in 3 week-post-MCAO rats. On the other hand, red neurons and perivascular edema were less compared to 48 and 72-hour-post-MCAO rats.Conclusion: Flame–blunted monofilament showed its efficacy in producing infarct area. The advantages of this technique are easy to perform with simple and less expensive modification of the monofilament. Conducting successful permanent occlusion with less mortality rate will give chances to do further research on stroke in chronic phase and its effect on novel treatment.

  11. Motor Cortex and Motor Cortical Interhemispheric Communication in Walking After Stroke: The Roles of Transcranial Magnetic Stimulation and Animal Models in Our Current and Future Understanding.

    Science.gov (United States)

    Charalambous, Charalambos C; Bowden, Mark G; Adkins, DeAnna L

    2016-01-01

    Despite the plethora of human neurophysiological research, the bilateral involvement of the leg motor cortical areas and their interhemispheric interaction during both normal and impaired human walking is poorly understood. Using transcranial magnetic stimulation (TMS), we have expanded our understanding of the role upper-extremity motor cortical areas play in normal movements and how stroke alters this role, and probed the efficacy of interventions to improve post-stroke arm function. However, similar investigations of the legs have lagged behind, in part, due to the anatomical difficulty in using TMS to stimulate the leg motor cortical areas. Additionally, leg movements are predominately bilaterally controlled and require interlimb coordination that may involve both hemispheres. The sensitive, but invasive, tools used in animal models of locomotion hold great potential for increasing our understanding of the bihemispheric motor cortical control of walking. In this review, we discuss 3 themes associated with the bihemispheric motor cortical control of walking after stroke: (a) what is known about the role of the bihemispheric motor cortical control in healthy and poststroke leg movements, (b) how the neural remodeling of the contralesional hemisphere can affect walking recovery after a stroke, and (c) what is the effect of behavioral rehabilitation training of walking on the neural remodeling of the motor cortical areas bilaterally. For each theme, we discuss how rodent models can enhance the present knowledge on human walking by testing hypotheses that cannot be investigated in humans, and how these findings can then be back-translated into the neurorehabilitation of poststroke walking. © The Author(s) 2015.

  12. Specific imaging of inflammation with the 18 kDa translocator protein ligand DPA-714 in animal models of epilepsy and stroke.

    Directory of Open Access Journals (Sweden)

    Denise Harhausen

    Full Text Available Inflammation is a pathophysiological hallmark of many diseases of the brain. Specific imaging of cells and molecules that contribute to cerebral inflammation is therefore highly desirable, both for research and in clinical application. The 18 kDa translocator protein (TSPO has been established as a suitable target for the detection of activated microglia/macrophages. A number of novel TSPO ligands have been developed recently. Here, we evaluated the high affinity TSPO ligand DPA-714 as a marker of brain inflammation in two independent animal models. For the first time, the specificity of radiolabeled DPA-714 for activated microglia/macrophages was studied in a rat model of epilepsy (induced using Kainic acid and in a mouse model of stroke (transient middle cerebral artery occlusion, tMCAO using high-resolution autoradiography and immunohistochemistry. Additionally, cold-compound blocking experiments were performed and changes in blood-brain barrier (BBB permeability were determined. Target-to-background ratios of 2 and 3 were achieved in lesioned vs. unaffected brain tissue in the epilepsy and tMCAO models, respectively. In both models, ligand uptake into the lesion corresponded well with the extent of Ox42- or Iba1-immunoreactive activated microglia/macrophages. In the epilepsy model, ligand uptake was almost completely blocked by pre-injection of DPA-714 and FEDAA1106, another high-affinity TSPO ligand. Ligand uptake was independent of the degree of BBB opening and lesion size in the stroke model. We provide further strong evidence that DPA-714 is a specific ligand to image activated microglia/macrophages in experimental models of brain inflammation.

  13. pH imaging reveals worsened tissue acidification in diffusion kurtosis lesion than the kurtosis/diffusion lesion mismatch in an animal model of acute stroke.

    Science.gov (United States)

    Wang, Enfeng; Wu, Yin; Cheung, Jerry S; Zhou, Iris Yuwen; Igarashi, Takahiro; Zhang, XiaoAn; Sun, Phillip Zhe

    2017-10-01

    Diffusion weighted imaging (DWI) has been commonly used in acute stroke examination, yet a portion of DWI lesion may be salvageable. Recently, it has been shown that diffusion kurtosis imaging (DKI) defines the most severely damaged DWI lesion that does not renormalize following early reperfusion. We postulated that the diffusion and kurtosis lesion mismatch experience heterogeneous hemodynamic and/or metabolic injury. We investigated tissue perfusion, pH, diffusion, kurtosis and relaxation from regions of the contralateral normal area, diffusion lesion, kurtosis lesion and their mismatch in an animal model of acute stroke. Our study revealed significant kurtosis and diffusion lesion volume mismatch (19.7 ± 10.7%, P mismatch, we showed lower pH in the kurtosis lesion (pH = 6.64 ± 0.12) from that of the kurtosis/diffusion lesion mismatch (6.84 ± 0.11, P mismatch agreed well with literature values for regions of ischemic core and penumbra, respectively. Our work documented initial evidence that DKI may reveal the heterogeneous metabolic derangement within the commonly used DWI lesion.

  14. A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model

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    Chen, C.C. [Department of Electrical Engineering, National Cheng-Kung University, Tainan, Taiwan (China); Chang, M.W. [Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan, Taiwan (China); Chang, C.P. [Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan (China); Chan, S.C.; Chang, W.Y.; Yang, C.L. [Department of Electrical Engineering, National Cheng-Kung University, Tainan, Taiwan (China); Lin, M.T. [Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan (China)

    2014-08-15

    We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

  15. A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model

    Directory of Open Access Journals (Sweden)

    C.C. Chen

    2014-10-01

    Full Text Available We developed a forced non-electric-shock running wheel (FNESRW system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h. An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS, an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05 and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

  16. Experimental hemorrhagic stroke: search for a better model

    OpenAIRE

    Yabluchanskiy, Andriy; Sawle, Philip; Homer-vanniasinkam, Shervanthi; Green, Colin; Motterlini, Roberto

    2010-01-01

    Hemorrhagic stroke is one of the least studied problems in the modern neurology. Development of the treatment leads to examination of the pathophysiology of the process, which mainly can be performed in animal models. Recent years few animal model of the hemorrhagic stroke have been proposed. In this review we discuss the differences and benefits of the existing models in the compliance with the process that take place in human patients with hemorrhagic stroke.

  17. Modelling Farm Animal Welfare

    Science.gov (United States)

    Collins, Lisa M.; Part, Chérie E.

    2013-01-01

    Simple Summary In this review paper we discuss the different modeling techniques that have been used in animal welfare research to date. We look at what questions they have been used to answer, the advantages and pitfalls of the methods, and how future research can best use these approaches to answer some of the most important upcoming questions in farm animal welfare. Abstract The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively) based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested. PMID:26487411

  18. Animal models of dementia

    DEFF Research Database (Denmark)

    Olsson, I. Anna S.; Sandøe, Peter

    2011-01-01

    This chapter aims to encourage scientists and others interested in the use of animal models of disease – specifically, in the study of dementia – to engage in ethical reflection. It opens with a general discussion of the moral acceptability of animal use in research. Three ethical approaches are ...

  19. Animal models of dementia

    DEFF Research Database (Denmark)

    Olsson, I. Anna S.; Sandøe, Peter

    2011-01-01

    This chapter aims to encourage scientists and others interested in the use of animal models of disease – specifically, in the study of dementia – to engage in ethical reflection. It opens with a general discussion of the moral acceptability of animal use in research. Three ethical approaches...

  20. Living with companion animals after stroke: experiences of older people in community and primary care nursing.

    OpenAIRE

    Johansson, Maria; Ahlström, Gerd; Jönsson, Ann-Cathrin

    2014-01-01

    Older people often have companion animals, and the significance of animals in human lives should be considered by nurses-particularly in relation to older people's health, which can be affected by diseases. The incidence of stroke increases with age and disabilities as a result of stroke are common. This study aimed to explore older people's experiences of living with companion animals after stroke, and their life situation with the animals in relation to the physical, psychological a...

  1. Animal models of tinnitus.

    Science.gov (United States)

    Brozoski, Thomas J; Bauer, Carol A

    2016-08-01

    Presented is a thematic review of animal tinnitus models from a functional perspective. Chronic tinnitus is a persistent subjective sound sensation, emergent typically after hearing loss. Although the sensation is experientially simple, it appears to have central a nervous system substrate of unexpected complexity that includes areas outside of those classically defined as auditory. Over the past 27 years animal models have significantly contributed to understanding tinnitus' complex neurophysiology. In that time, a diversity of models have been developed, each with its own strengths and limitations. None has clearly become a standard. Animal models trace their origin to the 1988 experiments of Jastreboff and colleagues. All subsequent models derive some of their features from those experiments. Common features include behavior-dependent psychophysical determination, acoustic conditions that contrast objective sound and silence, and inclusion of at least one normal-hearing control group. In the present review, animal models have been categorized as either interrogative or reflexive. Interrogative models use emitted behavior under voluntary control to indicate hearing. An example would be pressing a lever to obtain food in the presence of a particular sound. In this type of model animals are interrogated about their auditory sensations, analogous to asking a patient, "What do you hear?" These models require at least some training and motivation management, and reflect the perception of tinnitus. Reflexive models, in contrast, employ acoustic modulation of an auditory reflex, such as the acoustic startle response. An unexpected loud sound will elicit a reflexive motor response from many species, including humans. Although involuntary, acoustic startle can be modified by a lower-level preceding event, including a silent sound gap. Sound-gap modulation of acoustic startle appears to discriminate tinnitus in animals as well as humans, and requires no training or

  2. Animal models of sarcoidosis.

    Science.gov (United States)

    Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M

    2017-03-01

    Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.

  3. Animal Models of Glaucoma

    Directory of Open Access Journals (Sweden)

    Rachida A. Bouhenni

    2012-01-01

    Full Text Available Glaucoma is a heterogeneous group of disorders that progressively lead to blindness due to loss of retinal ganglion cells and damage to the optic nerve. It is a leading cause of blindness and visual impairment worldwide. Although research in the field of glaucoma is substantial, the pathophysiologic mechanisms causing the disease are not completely understood. A wide variety of animal models have been used to study glaucoma. These include monkeys, dogs, cats, rodents, and several other species. Although these models have provided valuable information about the disease, there is still no ideal model for studying glaucoma due to its complexity. In this paper we present a summary of most of the animal models that have been developed and used for the study of the different types of glaucoma, the strengths and limitations associated with each species use, and some potential criteria to develop a suitable model.

  4. ANIMAL MODELS IN SURGICAL

    African Journals Online (AJOL)

    ASSEMBLED BY

    1 Dept.of Veterinary Surgery and Medicine 2Veterinary Teaching Hospital Ahmadu Bello University. Zaria .... unnecessary suffering., Administration of poisons .... way that humans are. Vivisection/ Surgical Training And Research. Animal model use: In both the human and veterinary medical practice, there continue to be ...

  5. Critical Periods after Stroke Study: Translating animal stroke recovery experiments into a clinical trial

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    Alexander W Dromerick

    2015-04-01

    Full Text Available Introduction: 795,000 Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 hours of upper extremity therapy either immediately upon rehab admission, 2-3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test at one year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial.

  6. Critical periods after stroke study: translating animal stroke recovery experiments into a clinical trial

    Science.gov (United States)

    Dromerick, Alexander W.; Edwardson, Matthew A.; Edwards, Dorothy F.; Giannetti, Margot L.; Barth, Jessica; Brady, Kathaleen P.; Chan, Evan; Tan, Ming T.; Tamboli, Irfan; Chia, Ruth; Orquiza, Michael; Padilla, Robert M.; Cheema, Amrita K.; Mapstone, Mark E.; Fiandaca, Massimo S.; Federoff, Howard J.; Newport, Elissa L.

    2015-01-01

    Introduction: Seven hundred ninety-five thousand Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS) is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 h of upper extremity therapy either immediately upon rehab admission, 2–3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test (ARAT) at 1 year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial. PMID

  7. Animal models of sepsis.

    Science.gov (United States)

    Fink, Mitchell P

    2014-01-01

    Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, the animal models that have been used for this purpose have often yielded misleading findings. It is likely that there are multiple reasons for the discrepancies between the results obtained in tests of pharmacological agents in animal models of sepsis and the outcomes of human clinical trials. One of important reason may be that the changes in gene expression, which are triggered by trauma or infection, are different in mice, a commonly used species for preclinical testing, and humans. Additionally, many species, including mice and baboons, are remarkably resistant to the toxic effects of bacterial lipopolysaccharide, whereas humans are exquisitely sensitive. New approaches toward the use of animals for sepsis research are being investigated. But, at present, results from preclinical studies of new therapeutic agents for sepsis must be viewed with a degree of skepticism.

  8. GSK-3 as a Target for Lithium-induced Neuroprotection against Excitotoxicity in Neuronal Cultures and Animal Models of Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    De-Maw eChuang

    2011-08-01

    Full Text Available The mood stabilizer lithium inhibits glycogen synthase kinase-3 (GSK-3 directly or indirectly by enhancing serine phosphorylation of both alpha and beta isoforms. Lithium robustly protected primary brain neurons from glutamate-induced excitotoxicity; these actions were mimicked by other GSK-3 inhibitors or silencing/inhibiting GSK-3alpha and/or beta isoforms. Lithium rapidly activated Akt to enhance GSK-3 serine phosphorylation and to block glutamate-induced Akt inactivation. Lithium also upregulated Bcl-2 and suppressed glutamate-induced p53 and Bax. Induction of BDNF was required for lithium’s neuroprotection to occur. BDNF promoter IV was activated by GSK-3 inhibition using lithium or other drugs, or through gene silencing/inactivation of either isoform. Further, lithium’s neuroprotective effects were associated with inhibition of NMDA receptor-mediated calcium influx and downstream signaling. In rodent ischemic models, post-insult treatment with lithium decreased infarct volume, ameliorated neurological deficits and improved functional recovery. Upregulation of heat shock protein 70 (HSP70 and Bcl-2 as well as downregulation of p53 likely contributed to lithium’s protective effects. Delayed treatment with lithium improved functional MRI responses, which was accompanied by enhanced angiogenesis. Two GSK-3-regulated pro-angiogenic factors, matrix metalloproteinase-9 (MMP-9 and vascular endothelial growth factor were induced by lithium. Finally, lithium promoted migration of mesenchymal stem cells (MSCs by upregulation of MMP-9 through GSK-3beta inhibition. Notably, transplantation of lithium-primed MSCs into ischemic rats enhanced MSC migration to the injured brain regions and improved the neurological performance. Several other GSK-3 inhibitors have also been reported to be beneficial in rodent ischemic models. Together, GSK-3 inhibition is a rational strategy to combat ischemic stroke and other excitotoxicity-related brain disorders.

  9. Animal Models of Atherosclerosis

    Science.gov (United States)

    Getz, Godfrey S.; Reardon, Catherine A.

    2012-01-01

    Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits and non-human primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. While not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable. PMID:22383700

  10. Animal models of spondyloarthritis.

    Science.gov (United States)

    Lories, Rik J U

    2006-07-01

    The aim of this article is to review new insights into spondyloarthritis obtained in animal models during the last year. HLA-B27 misfolding has been demonstrated in HLA-B27/human beta2-microglobulin transgenic rats. HLA-B27 misfolding is associated with a typical unfolded protein stress response and with an interferon-response signature. Prebiotic treatment of these rats reduced colitis and arthritis. Proteoglycan-induced spondylitis is distinct from proteoglycan-induced arthritis. Specific susceptibility loci for proteoglycan-induced spondylitis have been demonstrated. Bone morphogenetic proteins are important in new cartilage and bone formation in ankylosing enthesitis. Psoriasis and psoriatic arthritis-like disease develops in conditional double JunB/c-Jun knockout mice. Insights into the molecular signaling pathways driving HLA-B27 associated spondylitis, autoimmune spondylitis, ankylosing enthesitis and psoriasis, resulting from animal models, identify new and specific therapeutic targets in spondyloarthritis.

  11. Animal models of sepsis

    OpenAIRE

    Fink, Mitchell P

    2013-01-01

    Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, ...

  12. Bone marrow stromal cell therapy for ischemic stroke: A meta-analysis of randomized control animal trials.

    Science.gov (United States)

    Wu, Qing; Wang, Yuexiang; Demaerschalk, Bart M; Ghimire, Saruna; Wellik, Kay E; Qu, Wenchun

    2017-04-01

    Background Results of animal studies assessing efficacy of bone marrow stromal cell therapy for ischemic stroke remain inconsistent. Aims The aims are to assess efficacy of bone marrow stromal cell therapy for ischemic stroke in animal studies. Methods Randomized controlled animal trials assessing efficacy of bone marrow stromal cell therapy were eligible. Stroke therapy academic industry round table was used to assess methodologic quality of included studies. Primary outcomes were total infarction volume and modified Neurological Severity Score. Multiple prespecified sensitivity analyses and subgroup analyses were conducted. Random effects models were used for meta-analysis. Results Thirty-three randomized animal trials were included with a total of 796 animals. The median quality score was 6 (interquartile range, 5-7). Bone marrow stromal cell therapy decreased total infarction volume (standardized mean difference, 0.897; 95% confidence interval, 0.553-1.241; P animals treated with bone marrow stromal cell and controls was 2.47 (95% confidence interval, 1.84-3.11; P animal studies. Conclusions Bone marrow stromal cell therapy significantly decreased total infarction volume and increased neural functional recovery in randomized controlled animal models of ischemic stroke.

  13. Animal Models of Hemophilia

    Science.gov (United States)

    Sabatino, Denise E.; Nichols, Timothy C.; Merricks, Elizabeth; Bellinger, Dwight A.; Herzog, Roland W.; Monahan, Paul E.

    2013-01-01

    The X-linked bleeding disorder hemophilia is caused by mutations in coagulation factor VIII (hemophilia A) or factor IX (hemophilia B). Unless prophylactic treatment is provided, patients with severe disease (less than 1% clotting activity) typically experience frequent spontaneous bleeds. Current treatment is largely based on intravenous infusion of recombinant or plasma-derived coagulation factor concentrate. More effective factor products are being developed. Moreover, gene therapies for sustained correction of hemophilia are showing much promise in pre-clinical studies and in clinical trials. These advances in molecular medicine heavily depend on availability of well-characterized small and large animal models of hemophilia, primarily hemophilia mice and dogs. Experiments in these animals represent important early and intermediate steps of translational research aimed at development of better and safer treatments for hemophilia, such a protein and gene therapies or immune tolerance protocols. While murine models are excellent for studies of large groups of animals using genetically defined strains, canine models are important for testing scale-up and for longer-term follow-up as well as for studies that require larger blood volumes. PMID:22137432

  14. Animal models of schizophrenia

    Science.gov (United States)

    Jones, CA; Watson, DJG; Fone, KCF

    2011-01-01

    Developing reliable, predictive animal models for complex psychiatric disorders, such as schizophrenia, is essential to increase our understanding of the neurobiological basis of the disorder and for the development of novel drugs with improved therapeutic efficacy. All available animal models of schizophrenia fit into four different induction categories: developmental, drug-induced, lesion or genetic manipulation, and the best characterized examples of each type are reviewed herein. Most rodent models have behavioural phenotype changes that resemble ‘positive-like’ symptoms of schizophrenia, probably reflecting altered mesolimbic dopamine function, but fewer models also show altered social interaction, and learning and memory impairment, analogous to negative and cognitive symptoms of schizophrenia respectively. The negative and cognitive impairments in schizophrenia are resistant to treatment with current antipsychotics, even after remission of the psychosis, which limits their therapeutic efficacy. The MATRICS initiative developed a consensus on the core cognitive deficits of schizophrenic patients, and recommended a standardized test battery to evaluate them. More recently, work has begun to identify specific rodent behavioural tasks with translational relevance to specific cognitive domains affected in schizophrenia, and where available this review focuses on reporting the effect of current and potential antipsychotics on these tasks. The review also highlights the need to develop more comprehensive animal models that more adequately replicate deficits in negative and cognitive symptoms. Increasing information on the neurochemical and structural CNS changes accompanying each model will also help assess treatments that prevent the development of schizophrenia rather than treating the symptoms, another pivotal change required to enable new more effective therapeutic strategies to be developed. LINKED ARTICLES This article is part of a themed issue on

  15. RODENT STROKE MODEL GUIDELINES FOR PRECLINICAL STROKE TRIALS (1ST EDITION)

    OpenAIRE

    Liu, Shimin; Zhen, Gehua; Meloni, Bruno P.; Campbell, Kym; Winn, H Richard

    2009-01-01

    Translational stroke research is a challenging task that needs long term team work of the stroke research community. Highly reproducible stroke models with excellent outcome consistence are essential for obtaining useful data from preclinical stroke trials as well as for improving inter-lab comparability. However, our review of literature shows that the infarct variation coefficient of commonly performed stroke models ranges from 5% to 200%. An overall improvement of the commonly used stroke ...

  16. Living with companion animals after stroke: experiences of older people in community and primary care nursing.

    Science.gov (United States)

    Johansson, Maria; Ahlström, Gerd; Jönsson, Ann-Cathrin

    2014-12-01

    Older people often have companion animals, and the significance of animals in human lives should be considered by nurses-particularly in relation to older people's health, which can be affected by diseases. The incidence of stroke increases with age and disabilities as a result of stroke are common. This study aimed to explore older people's experiences of living with companion animals after stroke, and their life situation with the animals in relation to the physical, psychological and social aspects of recovery after stroke. The study was performed using individual interviews approximately 2 years after stroke with 17 participants (10 women and 7 men) aged 62-88 years. An overarching theme arising from the content analysis was contribution to a meaningful life. This theme was generated from four categories: motivation for physical and psychosocial recovery after stroke; someone to care for who cares for you; animals as family members; and providers of safety and protection. The main conclusion was that companion animals are experienced as physical and psychosocial contributors to recovery and a meaningful life after stroke.

  17. Animal Models of Neuropsychiatric Disorders

    Science.gov (United States)

    Nestler, Eric J.; Hyman, Steven E.

    2013-01-01

    Modeling of human neuropsychiatric disorders in animals is extremely challenging given the subjective nature of many key symptoms, the lack of biomarkers and objective diagnostic tests, and the early state of the relevant neurobiology and genetics. Nonetheless, progress in understanding pathophysiology and in treatment development would benefit greatly from improved animal models. Here we review the current state of animal models of mental illness, with a focus on schizophrenia, depression, and bipolar disorder. We argue for areas of focus that might increase the likelihood of creating more useful models, at least for some disorders, and for explicit guidelines when animal models are reported. PMID:20877280

  18. ANIMAL MODELS FOR IMMUNOTOXICITY

    Science.gov (United States)

    Greater susceptibility to infection is a hallmark of compromised immune function in humans and animals, and is often considered the benchmark against which the predictive value of immune function tests are compared. This focus of this paper is resistance to infection with the pa...

  19. Publication bias in reports of animal stroke studies leads to major overstatement of efficacy.

    Directory of Open Access Journals (Sweden)

    Emily S Sena

    2010-03-01

    Full Text Available The consolidation of scientific knowledge proceeds through the interpretation and then distillation of data presented in research reports, first in review articles and then in textbooks and undergraduate courses, until truths become accepted as such both amongst "experts" and in the public understanding. Where data are collected but remain unpublished, they cannot contribute to this distillation of knowledge. If these unpublished data differ substantially from published work, conclusions may not reflect adequately the underlying biological effects being described. The existence and any impact of such "publication bias" in the laboratory sciences have not been described. Using the CAMARADES (Collaborative Approach to Meta-analysis and Review of Animal Data in Experimental Studies database we identified 16 systematic reviews of interventions tested in animal studies of acute ischaemic stroke involving 525 unique publications. Only ten publications (2% reported no significant effects on infarct volume and only six (1.2% did not report at least one significant finding. Egger regression and trim-and-fill analysis suggested that publication bias was highly prevalent (present in the literature for 16 and ten interventions, respectively in animal studies modelling stroke. Trim-and-fill analysis suggested that publication bias might account for around one-third of the efficacy reported in systematic reviews, with reported efficacy falling from 31.3% to 23.8% after adjustment for publication bias. We estimate that a further 214 experiments (in addition to the 1,359 identified through rigorous systematic review; non publication rate 14% have been conducted but not reported. It is probable that publication bias has an important impact in other animal disease models, and more broadly in the life sciences.

  20. Stroke education using an animated cartoon and a manga for junior high school students.

    Science.gov (United States)

    Shigehatake, Yuya; Yokota, Chiaki; Amano, Tatsuo; Tomii, Yasuhiro; Inoue, Yasuteru; Hagihara, Takaaki; Toyoda, Kazunori; Minematsu, Kazuo

    2014-07-01

    We investigated whether junior high school students could be educated regarding stroke with an animated cartoon and a Manga that we produced for the purpose of dissemination of this knowledge. We produced a 10-minute animated cartoon and a Manga that provided information regarding stroke risk factors, stroke signs and symptoms, and awareness to immediately contact emergent medical service (EMS) on identification of stroke signs and symptoms. From December 2011 to March 2012, 493 students in 15 classes of the first grade (age 12-13 years) of 3 junior high schools were enrolled in the study. Each subject watched the animated cartoon and read the Manga; this was referred to as "training." Lessons about stroke were not given. Questionnaires on stroke knowledge were evaluated at baseline, immediately after the training, and 3 months after the training. The proportion of correct answers given immediately after the training was higher for all questions, except those related to arrhythmia, compared with baseline. Percentage of correct answers given at 3 months was higher than that at baseline in questions related to facial palsy (75% versus 33%), speech disturbance (91% versus 60%), hemiplegia (79% versus 52%), numbness of 1 side (58% versus 51%), calling for EMS (90% versus 85%), alcohol intake (96% versus 72%), and smoking (69% versus 54%). At 3 months after the training, 56% of students answered the FAST (facial droop, arm weakness, speech disturbance, time to call for EMS) mnemonic correctly. Stroke education using these teaching aids of the animated cartoon and the Manga improved stroke knowledge in junior high school students. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. Effects of stroke education using an animated cartoon and a manga on elementary school children.

    Science.gov (United States)

    Sakamoto, Yuki; Yokota, Chiaki; Miyashita, Fumio; Amano, Tatsuo; Shigehatake, Yuya; Oyama, Satoshi; Itagaki, Naruhiko; Okumura, Kosuke; Toyoda, Kazunori; Minematsu, Kazuo

    2014-08-01

    Stroke education for the youth is expected to reduce prehospital delay by informing the bystander of appropriate action to take and providing knowledge to prevent onset of stroke in future. Previously, we developed effective teaching materials consisting of an animated cartoon and a Manga for junior high school students. The aim of this study was to evaluate the feasibility and effectiveness of our educational materials for stroke education taught by schoolteachers to elementary school children. Using our teaching materials, a 30-minute lesson was given by trained general schoolteachers. Questionnaires on stroke knowledge (symptoms and risk factors) and action to take on identification of suspected stroke symptoms were filled out by school children before, immediately after, and at 3 months after completion of the lesson. A total of 219 children (aged 10 or 11 years) received the stroke lesson. Stroke knowledge significantly increased immediately after the lesson compared with before (symptoms, P Manga that was previously used for junior high school students was feasible for elementary school children. However, revision of the materials is required for better retention of stroke knowledge for children. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  2. The role of sleep in recovery following ischemic stroke: A review of human and animal data

    Directory of Open Access Journals (Sweden)

    Simone B. Duss

    2017-01-01

    Full Text Available Despite advancements in understanding the pathophysiology of stroke and the state of the art in acute management of afflicted patients as well as in subsequent neurorehabilitation training, stroke remains the most common neurological cause of long-term disability in adulthood. To enhance stroke patients’ independence and well-being it is necessary, therefore, to consider and develop new therapeutic strategies and approaches. We postulate that sleep might play a pivotal role in neurorehabilitation following stroke. Over the last two decades compelling evidence for a major function of sleep in neuroplasticity and neural network reorganization underlying learning and memory has evolved. Training and learning of new motor skills and knowledge can modulate the characteristics of subsequent sleep, which additionally can improve memory performance. While healthy sleep appears to support neuroplasticity resulting in improved learning and memory, disturbed sleep following stroke in animals and humans can impair stroke outcome. In addition, sleep disorders such as sleep disordered breathing, insomnia, and restless legs syndrome are frequent in stroke patients and associated with worse recovery outcomes. Studies investigating the evolution of post-stroke sleep changes suggest that these changes might also reflect neural network reorganization underlying functional recovery. Experimental and clinical studies provide evidence that pharmacological sleep promotion in rodents and treatment of sleep disorders in humans improves functional outcome following stroke. Taken together, there is accumulating evidence that sleep represents a “plasticity state” in the process of recovery following ischemic stroke. However, to test the key role of sleep and sleep disorders for stroke recovery and to better understand the underlying molecular mechanisms, experimental research and large-scale prospective studies in humans are necessary. The effects of hospital

  3. Animal Models for Candidiasis

    Science.gov (United States)

    Conti, Heather R.; Huppler, Anna R.; Whibley, Natasha; Gaffen, Sarah L.

    2014-01-01

    Multiple forms of candidiasis are clinically important in humans. Established murine models of disseminated, oropharyngeal, vaginal, and cutaneous candidiasis caused by Candida albicans are described in this unit. Detailed materials and methods for C. albicans growth and detection are also described. PMID:24700323

  4. Animal Models of Bacterial Keratitis

    Science.gov (United States)

    Marquart, Mary E.

    2011-01-01

    Bacterial keratitis is a disease of the cornea characterized by pain, redness, inflammation, and opacity. Common causes of this disease are Pseudomonas aeruginosa and Staphylococcus aureus. Animal models of keratitis have been used to elucidate both the bacterial factors and the host inflammatory response involved in the disease. Reviewed herein are animal models of bacterial keratitis and some of the key findings in the last several decades. PMID:21274270

  5. Animal models for human diseases.

    Science.gov (United States)

    Rust, J H

    1982-01-01

    The use of animal models for the study of human disease is, for the most part, a recent development. This discussion of the use of animal models for human diseases directs attention to the sterile period, early advances, some personal experiences, the human as the model, biological oddities among common laboratory animals, malignancies in laboratory animals, problems created by federal regulations, cancer tests with animals, and what the future holds in terms of the use of animal models as an aid to understanding human disease. In terms of early use of animal models, there was a school of rabbis, some of whom were also physicians, in Babylon who studied and wrote extensively on ritual slaughter and the suitability of birds and beasts for food. Considerable detailed information on animal pathology, physiology, anatomy, and medicine in general can be found in the Soncino Babylonian Talmudic Translations. The 1906 edition of the "Jewish Encyclopedia," has been a rich resource. Although it has not been possible to establish what diseases of animals were studied and their relationship to the diseases of humans, there are fascinating clues to pursue, despite the fact that these were sterile years for research in medicine. The quotation from the Talmud is of interest: "The medical knowledge of the Talmudist was based upon tradition, the dissection of human bodies, observation of disease and experiments upon animals." A bright light in the lackluster years of medical research was provided by Galen, considered the originator of research in physiology and anatomy. His dissection of animals and work on apes and other lower animals were models for human anatomy and physiology and the bases for many treatises. Yet, Galen never seemed to suggest that animals could serve as models for human diseases. Most early physicians who can be considered to have been students of disease developed their medical knowledge by observing the sick under their care. 1 early medical investigator

  6. Animal models in myopia research.

    Science.gov (United States)

    Schaeffel, Frank; Feldkaemper, Marita

    2015-11-01

    Our current understanding of the development of refractive errors, in particular myopia, would be substantially limited had Wiesel and Raviola not discovered by accident that monkeys develop axial myopia as a result of deprivation of form vision. Similarly, if Josh Wallman and colleagues had not found that simple plastic goggles attached to the chicken eye generate large amounts of myopia, the chicken model would perhaps not have become such an important animal model. Contrary to previous assumptions about the mechanisms of myopia, these animal models suggested that eye growth is visually controlled locally by the retina, that an afferent connection to the brain is not essential and that emmetropisation uses more sophisticated cues than just the magnitude of retinal blur. While animal models have shown that the retina can determine the sign of defocus, the underlying mechanism is still not entirely clear. Animal models have also provided knowledge about the biochemical nature of the signal cascade converting the output of retinal image processing to changes in choroidal thickness and scleral growth; however, a critical question was, and still is, can the results from animal models be applied to myopia in children? While the basic findings from chickens appear applicable to monkeys, some fundamental questions remain. If eye growth is guided by visual feedback, why is myopic development not self-limiting? Why does undercorrection not arrest myopic progression even though positive lenses induce myopic defocus, which leads to the development of hyperopia in emmetropic animals? Why do some spectacle or contact lens designs reduce myopic progression and others not? It appears that some major differences exist between animals reared with imposed defocus and children treated with various optical corrections, although without the basic knowledge obtained from animal models, we would be lost in an abundance of untestable hypotheses concerning human myopia. © 2015 Optometry

  7. Animal models of pituitary neoplasia

    OpenAIRE

    Lines, K.E.; Stevenson, M.; Thakker, R.V.

    2016-01-01

    Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal mod...

  8. XX. Animal models of pneumocystosis

    DEFF Research Database (Denmark)

    Dei-Cas, E.; Brun-Pascaud, M.; Bille-Hansen, Vivi

    1998-01-01

    As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were...... a source of parasites taxonomically related to P. carinii sp. f hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown......, are important drawbacks of the corticosteroid-treated models. For these reasons, inoculated animal models of PCP were developed. The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis...

  9. Animal models of pituitary neoplasia

    Science.gov (United States)

    Lines, K.E.; Stevenson, M.; Thakker, R.V.

    2016-01-01

    Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

  10. Animal welfare and use of silkworm as a model animal.

    Science.gov (United States)

    Sekimizu, N; Paudel, A; Hamamoto, H

    2012-08-01

    Sacrificing model animals is required for developing effective drugs before being used in human beings. In Japan today, at least 4,210,000 mice and other mammals are sacrificed to a total of 6,140,000 per year for the purpose of medical studies. All the animals treated in Japan, including test animals, are managed under control of "Act on Welfare and Management of Animals". Under the principle of this Act, no person shall kill, injure, or inflict cruelty on animals without due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal". If we can make use of invertebrate animals in testing instead of vertebrate ones, that would be a remarkable solution for the issue of animal welfare. Furthermore, there are numerous advantages of using invertebrate animal models: less space and small equipment are enough for taking care of a large number of animals and thus are cost-effective, they can be easily handled, and many biological processes and genes are conserved between mammals and invertebrates. Today, many invertebrates have been used as animal models, but silkworms have many beneficial traits compared to mammals as well as other insects. In a Genome Pharmaceutical Institute's study, we were able to achieve a lot making use of silkworms as model animals. We would like to suggest that pharmaceutical companies and institutes consider the use of the silkworm as a model animal which is efficacious both for financial value by cost cutting and ethical aspects in animals' welfare.

  11. MR Vascular Fingerprinting in Stroke and Brain Tumors Models.

    Science.gov (United States)

    Lemasson, B; Pannetier, N; Coquery, N; Boisserand, Ligia S B; Collomb, Nora; Schuff, N; Moseley, M; Zaharchuk, G; Barbier, E L; Christen, T

    2016-11-24

    In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases.

  12. Small animal models of xenotransplantation.

    Science.gov (United States)

    Wang, Hao

    2012-01-01

    Organ transplantation has become a successful and acceptable treatment for end-stage organ failure. Such success has allowed transplant patients to resume a normal lifestyle. The demands for transplantation have been steadily increasing, as more patients and new diseases are being deemed eligible for treatment via transplantation. However, it is clear that human organs will never meet the increasing demand of transplantation. Therefore, scientists must continue to pursue alternative therapies and explore new treatments to meet the growing demand for the limited number of organs available. Transplanting organs from animals into humans (xenotransplantation) is one such therapy. The observed enthusiasm for xenotransplantation, irrespective of the severe shortage of human organs and tissues available for transplantation, can be said to stem from at least two factors. First, there is the possibility that animal organs and tissues might be less susceptible than those of humans to the recurrence of disease processes. Second, a xenograft might be used as a vehicle for introducing novel genes or biochemical processes which could be of therapeutic value for the transplant recipient.To date, millions of lives have been saved by organ transplantation. These remarkable achievements would have been impossible without experimental transplantation research in animal models. Presently, more than 95% of organ transplantation research projects are carried out using rodents, such as rats and mice. The key factor to ensure the success of these experiments lies in state-of-the art experimental surgery. Small animal models offer unique advantages for the mechanistic study of xenotransplantation rejection. Currently, multiple models have been developed for investigating the different stages of immunological barriers in xenotransplantation. In this chapter, we describe six valuable small animal models that have been used in xenotransplantation research. The methodology for the small animal

  13. Modeling Dynamic Regulatory Processes in Stroke

    Science.gov (United States)

    McDermott, Jason E.; Jarman, Kenneth; Taylor, Ronald; Lancaster, Mary; Shankaran, Harish; Vartanian, Keri B.; Stevens, Susan L.; Stenzel-Poore, Mary P.; Sanfilippo, Antonio

    2012-01-01

    The ability to examine the behavior of biological systems in silico has the potential to greatly accelerate the pace of discovery in diseases, such as stroke, where in vivo analysis is time intensive and costly. In this paper we describe an approach for in silico examination of responses of the blood transcriptome to neuroprotective agents and subsequent stroke through the development of dynamic models of the regulatory processes observed in the experimental gene expression data. First, we identified functional gene clusters from these data. Next, we derived ordinary differential equations (ODEs) from the data relating these functional clusters to each other in terms of their regulatory influence on one another. Dynamic models were developed by coupling these ODEs into a model that simulates the expression of regulated functional clusters. By changing the magnitude of gene expression in the initial input state it was possible to assess the behavior of the networks through time under varying conditions since the dynamic model only requires an initial starting state, and does not require measurement of regulatory influences at each time point in order to make accurate predictions. We discuss the implications of our models on neuroprotection in stroke, explore the limitations of the approach, and report that an optimized dynamic model can provide accurate predictions of overall system behavior under several different neuroprotective paradigms. PMID:23071432

  14. Modeling dynamic regulatory processes in stroke.

    Directory of Open Access Journals (Sweden)

    Jason E McDermott

    Full Text Available The ability to examine the behavior of biological systems in silico has the potential to greatly accelerate the pace of discovery in diseases, such as stroke, where in vivo analysis is time intensive and costly. In this paper we describe an approach for in silico examination of responses of the blood transcriptome to neuroprotective agents and subsequent stroke through the development of dynamic models of the regulatory processes observed in the experimental gene expression data. First, we identified functional gene clusters from these data. Next, we derived ordinary differential equations (ODEs from the data relating these functional clusters to each other in terms of their regulatory influence on one another. Dynamic models were developed by coupling these ODEs into a model that simulates the expression of regulated functional clusters. By changing the magnitude of gene expression in the initial input state it was possible to assess the behavior of the networks through time under varying conditions since the dynamic model only requires an initial starting state, and does not require measurement of regulatory influences at each time point in order to make accurate predictions. We discuss the implications of our models on neuroprotection in stroke, explore the limitations of the approach, and report that an optimized dynamic model can provide accurate predictions of overall system behavior under several different neuroprotective paradigms.

  15. Stroke survivors' endorsement of a "stress belief model" of stroke prevention predicts control of risk factors for recurrent stroke.

    Science.gov (United States)

    Phillips, L Alison; Tuhrim, Stanley; Kronish, Ian M; Horowitz, Carol R

    2014-01-01

    Perceptions that stress causes and stress-reduction controls hypertension have been associated with poorer blood pressure (BP) control in hypertension populations. The current study investigated these "stress-model perceptions" in stroke survivors regarding prevention of recurrent stroke and the influence of these perceptions on patients' stroke risk factor control. Stroke and transient ischemic attack survivors (N=600) participated in an in-person interview in which they were asked about their beliefs regarding control of future stroke; BP and cholesterol were measured directly after the interview. Counter to expectations, patients who endorsed a "stress-model" but not a "medication-model" of stroke prevention were in better control of their stroke risk factors (BP and cholesterol) than those who endorsed a medication-model but not a stress-model of stroke prevention (OR for poor control=.54, Wald statistic=6.07, p=.01). This result was not explained by between group differences in patients' reported medication adherence. The results have implications for theory and practice, regarding the role of stress belief models and acute cardiac events, compared to chronic hypertension.

  16. Animal models for auditory streaming

    Science.gov (United States)

    Itatani, Naoya

    2017-01-01

    Sounds in the natural environment need to be assigned to acoustic sources to evaluate complex auditory scenes. Separating sources will affect the analysis of auditory features of sounds. As the benefits of assigning sounds to specific sources accrue to all species communicating acoustically, the ability for auditory scene analysis is widespread among different animals. Animal studies allow for a deeper insight into the neuronal mechanisms underlying auditory scene analysis. Here, we will review the paradigms applied in the study of auditory scene analysis and streaming of sequential sounds in animal models. We will compare the psychophysical results from the animal studies to the evidence obtained in human psychophysics of auditory streaming, i.e. in a task commonly used for measuring the capability for auditory scene analysis. Furthermore, the neuronal correlates of auditory streaming will be reviewed in different animal models and the observations of the neurons’ response measures will be related to perception. The across-species comparison will reveal whether similar demands in the analysis of acoustic scenes have resulted in similar perceptual and neuronal processing mechanisms in the wide range of species being capable of auditory scene analysis. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044022

  17. Animal models of papillomavirus pathogenesis.

    Science.gov (United States)

    Campo, M Saveria

    2002-11-01

    Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have been studied both as agents of disease in animals and as models of human PV infection. In addition to the study of PV infection in whole animals, in vitro studies with animal PV proteins have contributed greatly to the understanding of the mechanisms of cell transformation. Animal PVs cause distressing diseases in both farm and companion animals, such as teat papillomatosis in cattle, equine sarcoids and canine oral papillomatosis and there is an urgent need to understand the pathogenesis of these problematic infections. Persistent and florid teat papillomatosis in cows can lead to mastitis, prevent the suckling of calves and make milking impossible; heavily affected animals are culled and so occasionally are whole herds. Equine sarcoids are often recurrent and untreatable and lead to loss of valuable animals. Canine oral papillomatosis can be very extensive and persistent and lead to great distress. Thus the continuing research in the biology of animal PVs is amply justified. BPVs and CRPV have been for many years the model systems with which to study the biology of HPV. Induction of papillomas and their neoplastic progression has been experimentally demonstrated and reproduced in cattle and rabbits, and virus-cofactor interactions have been elucidated in these systems. With the advancements in molecular and cell culture techniques, the direct study of HPV has become less

  18. Animal Models of Zika Virus

    Science.gov (United States)

    Bradley, Michael P; Nagamine, Claude M

    2017-01-01

    Zika virus has garnered great attention over the last several years, as outbreaks of the disease have emerged throughout the Western Hemisphere. Until quite recently Zika virus was considered a fairly benign virus, with limited clinical severity in both people and animals. The size and scope of the outbreak in the Western Hemisphere has allowed for the identification of severe clinical disease that is associated with Zika virus infection, most notably microcephaly among newborns, and an association with Guillian–Barré syndrome in adults. This recent association with severe clinical disease, of which further analysis strongly suggested causation by Zika virus, has resulted in a massive increase in the amount of both basic and applied research of this virus. Both small and large animal models are being used to uncover the pathogenesis of this emerging disease and to develop vaccine and therapeutic strategies. Here we review the animal-model–based Zika virus research that has been performed to date. PMID:28662753

  19. XX. Animal models of pneumocystosis

    DEFF Research Database (Denmark)

    Dei-Cas, E.; Brun-Pascaud, M.; Bille-Hansen, Vivi

    1998-01-01

    As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were...... the host immune response as well as Pneumocystis-surfactant interactions. Pigs and horses also develop spontaneous PCP. Treated with corticosteroids, piglets develop extensive PCP and could be used as a non-rodent model. Pneumocystis was detected in many non-human primates. Primates could represent...... a source of parasites taxonomically related to P. carinii sp. f hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown...

  20. Animal models of drug addiction.

    Science.gov (United States)

    García Pardo, María Pilar; Roger Sánchez, Concepción; De la Rubia Ortí, José Enrique; Aguilar Calpe, María Asunción

    2017-09-29

    The development of animal models of drug reward and addiction is an essential factor for progress in understanding the biological basis of this disorder and for the identification of new therapeutic targets. Depending on the component of reward to be studied, one type of animal model or another may be used. There are models of reinforcement based on the primary hedonic effect produced by the consumption of the addictive substance, such as the self-administration (SA) and intracranial self-stimulation (ICSS) paradigms, and there are models based on the component of reward related to associative learning and cognitive ability to make predictions about obtaining reward in the future, such as the conditioned place preference (CPP) paradigm. In recent years these models have incorporated methodological modifications to study extinction, reinstatement and reconsolidation processes, or to model specific aspects of addictive behavior such as motivation to consume drugs, compulsive consumption or drug seeking under punishment situations. There are also models that link different reinforcement components or model voluntary motivation to consume (two-bottle choice, or drinking in the dark tests). In short, innovations in these models allow progress in scientific knowledge regarding the different aspects that lead individuals to consume a drug and develop compulsive consumption, providing a target for future treatments of addiction.

  1. Modelling group dynamic animal movement

    DEFF Research Database (Denmark)

    Langrock, Roland; Hopcraft, J. Grant C.; Blackwell, Paul G.

    2014-01-01

    in non-ideal scenarios, we show that generally the estimation of models of this type is both feasible and ecologically informative. We illustrate the approach using real movement data from 11 reindeer (Rangifer tarandus). Results indicate a directional bias towards a group centroid for reindeer......Group dynamic movement is a fundamental aspect of many species' movements. The need to adequately model individuals' interactions with other group members has been recognised, particularly in order to differentiate the role of social forces in individual movement from environmental factors. However......, to date, practical statistical methods which can include group dynamics in animal movement models have been lacking. We consider a flexible modelling framework that distinguishes a group-level model, describing the movement of the group's centre, and an individual-level model, such that each individual...

  2. Persistent Penumbra in a Rabbit Stroke Model: Incidence and Histologic Characteristics

    Directory of Open Access Journals (Sweden)

    Leah J. Hennings

    2011-01-01

    Full Text Available Duration and extent of penumbra determine the window and brain volume in which interventions may save injured tissue after stroke. Understanding the penumbra in animals is necessary in order to design models that translate to effective clinical therapies. New Zealand white rabbits were embolized with aged autologous clot (n=23 or insoluble microspheres (n=21. To examine effects of treatment on penumbra, sphere-stroked animals were treated with 3 μm microbubbles plus ultrasound (n=19. Rabbits were euthanized at 4 or 24 hr. Infarct volume was measured following triphenyltetrazolium chloride (TTC staining of brain sections. Penumbra was visualized using immunostaining of pimonidazole injected fifteen minutes prior to euthanasia. Potentially reversible penumbra was present in 14.3% stroked rabbits at 4 hours and 15.7% at 24 hours after embolic stroke and represented up to 35% of total lost tissue. Intervention at up to 24 hours may benefit a significant patient population.

  3. Animal Models of Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Domenico Santoro

    2014-12-01

    Full Text Available Allergic diseases have great impact on the quality of life of both people and domestic animals. They are increasing in prevalence in both animals and humans, possibly due to the changed lifestyle conditions and the decreased exposure to beneficial microorganisms. Dogs, in particular, suffer from environmental skin allergies and develop a clinical presentation which is very similar to the one of children with eczema. Thus, dogs are a very useful species to improve our understanding on the mechanisms involved in people’s allergies and a natural model to study eczema. Animal models are frequently used to elucidate mechanisms of disease and to control for confounding factors which are present in studies with patients with spontaneously occurring disease and to test new therapies that can be beneficial in both species. It has been found that drugs useful in one species can also have benefits in other species highlighting the importance of a comprehensive understanding of diseases across species and the value of comparative studies. The purpose of the current article is to review allergic diseases across species and to focus on how these diseases compare to the counterpart in people.

  4. Animal Models of Periventricular Leukomalacia

    Science.gov (United States)

    Choi, Ehn-Kyoung; Park, Dongsun; Kim, Tae Kyun; Lee, Sun Hee; Bae, Dae-Kwon; Yang, Goeun; Yang, Yun-Hui; Kyung, Jangbeen; Kim, Dajeong; Lee, Woo Ryoung; Suh, Jun-Gyo; Jeong, Eun-Suk; Kim, Seung U.

    2011-01-01

    Periventricular leukomalacia, specifically characterized as white matter injury, in neonates is strongly associated with the damage of pre-myelinating oligodendrocytes. Clinical data suggest that hypoxia-ischemia during delivery and intrauterine or neonatal infection-inflammation are important factors in the etiology of periventricular leukomalacia including cerebral palsy, a serious case exhibiting neurobehavioral deficits of periventricular leukomalacia. In order to explore the pathophysiological mechanisms of white matter injury and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, novel animal models have been developed using hypoperfusion, microbes or bacterial products (lipopolysaccharide) and excitotoxins. Such efforts have developed rat models that produce predominantly white matter lesions by adopting combined hypoxia-ischemia technique on postnatal days 1-7, in which unilateral or bilateral carotid arteries of animals are occluded (ischemia) followed by 1-2 hour exposure to 6-8% oxygen environment (hypoxia). Furthermore, low doses of lipopolysaccharide that by themselves have no adverse-effects in 7-day-old rats, dramatically increase brain injury to hypoxic-ischemic challenge, implying that inflammation sensitizes the immature central nervous system. Therefore, among numerous models of periventricular leukomalacia, combination of hypoxia-ischemia-lipopolysaccharide might be one of the most-acceptable rodent models to induce extensive white matter injury and ensuing neurobehavioral deficits for the evaluation of candidate therapeutics. PMID:21826166

  5. Animal models of RLS phenotypes.

    Science.gov (United States)

    Allen, Richard P; Donelson, Nathan C; Jones, Byron C; Li, Yuqing; Manconi, Mauro; Rye, David B; Sanyal, Subhabrata; Winkelmann, Juliane

    2017-03-01

    Restless legs syndrome (RLS) is a complex disorder that involves sensory and motor systems. The major pathophysiology of RLS is low iron concentration in the substantia nigra containing the cell bodies of dopamine neurons that project to the striatum, an area that is crucial for modulating movement. People who have RLS often present with normal iron values outside the brain; recent studies implicate several genes are involved in the syndrome. Like most complex diseases, animal models usually do not faithfully capture the full phenotypic spectrum of "disease," which is a uniquely human construct. Nonetheless, animal models have proven useful in helping to unravel the complex pathophysiology of diseases such as RLS and suggesting novel treatment paradigms. For example, hypothesis-independent genome-wide association studies (GWAS) have identified several genes as increasing the risk for RLS, including BTBD9. Independently, the murine homolog Btbd9 was identified as a candidate gene for iron regulation in the midbrain in mice. The relevance of the phenotype of another of the GWAS identified genes, MEIS1, has also been explored. The role of Btbd9 in iron regulation and RLS-like behaviors has been further evaluated in mice carrying a null mutation of the gene and in fruit flies when the BTBD9 protein is degraded. The BTBD9 and MEIS1 stories originate from human GWAS research, supported by work in a genetic reference population of mice (forward genetics) and further verified in mice, fish flies, and worms. Finally, the role of genetics is further supported by an inbred mouse strain that displays many of the phenotypic characteristics of RLS. The role of animal models of RLS phenotypes is also extended to include periodic limb movements. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Association between acute statin therapy, survival, and improved functional outcome after ischemic stroke: the North Dublin Population Stroke Study.

    LENUS (Irish Health Repository)

    2011-04-01

    Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study.

  7. Stroke Lesions in a Large Upper Limb Rehabilitation Trial Cohort Rarely Match Lesions in Common Preclinical Models.

    Science.gov (United States)

    Edwardson, Matthew A; Wang, Ximing; Liu, Brent; Ding, Li; Lane, Christianne J; Park, Caron; Nelsen, Monica A; Jones, Theresa A; Wolf, Steven L; Winstein, Carolee J; Dromerick, Alexander W

    2017-06-01

    Stroke patients with mild-moderate upper extremity motor impairments and minimal sensory and cognitive deficits provide a useful model to study recovery and improve rehabilitation. Laboratory-based investigators use lesioning techniques for similar goals. To determine whether stroke lesions in an upper extremity rehabilitation trial cohort match lesions from the preclinical stroke recovery models used to drive translational research. Clinical neuroimages from 297 participants enrolled in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study were reviewed. Images were characterized based on lesion type (ischemic or hemorrhagic), volume, vascular territory, depth (cortical gray matter, cortical white matter, subcortical), old strokes, and leukoaraiosis. Lesions were compared with those of preclinical stroke models commonly used to study upper limb recovery. Among the ischemic stroke participants, median infarct volume was 1.8 mL, with most lesions confined to subcortical structures (61%) including the anterior choroidal artery territory (30%) and the pons (23%). Of ICARE participants, stroke patients, but they represent a clinically and scientifically important subgroup. Compared with lesions in general stroke populations and widely studied animal models of recovery, ICARE participants had smaller, more subcortically based strokes. Improved preclinical-clinical translational efforts may require better alignment of lesions between preclinical and human stroke recovery models.

  8. A surgical model of permanent and transient middle cerebral artery stroke in the sheep.

    Directory of Open Access Journals (Sweden)

    Adam J Wells

    Full Text Available BACKGROUND: Animal models are essential to study the pathophysiological changes associated with focal occlusive stroke and to investigate novel therapies. Currently used rodent models have yielded little clinical success, however large animal models may provide a more suitable alternative to improve clinical translation. We sought to develop a model of acute proximal middle cerebral artery (MCA ischemic stroke in sheep, including both permanent occlusion and transient occlusion with reperfusion. MATERIALS AND METHODS: 18 adult male and female Merino sheep were randomly allocated to one of three groups (n = 6/gp: 1 sham surgery; 2 permanent proximal MCA occlusion (MCAO; or 3 temporary MCAO with aneurysm clip. All animals had invasive arterial blood pressure, intracranial pressure and brain tissue oxygen monitoring. At 4 h following vessel occlusion or sham surgery animals were killed by perfusion fixation. Brains were processed for histopathological examination and infarct area determination. 6 further animals were randomized to either permanent (n = 3 or temporary MCAO (n = 3 and then had magnetic resonance imaging (MRI at 4 h after MCAO. RESULTS: Evidence of ischemic injury in an MCA distribution was seen in all stroke animals. The ischemic lesion area was significantly larger after permanent (28.8% compared with temporary MCAO (14.6%. Sham animals demonstrated no evidence of ischemic injury. There was a significant reduction in brain tissue oxygen partial pressure after permanent vessel occlusion between 30 and 210 mins after MCAO. MRI at 4 h demonstrated complete proximal MCA occlusion in the permanent MCAO animals with a diffusion deficit involving the whole right MCA territory, whereas temporary MCAO animals demonstrated MRA evidence of flow within the right MCA and smaller predominantly cortical diffusion deficits. CONCLUSIONS: Proximal MCAO can be achieved in an ovine model of stroke via a surgical approach. Permanent

  9. Animal models and conserved processes

    Directory of Open Access Journals (Sweden)

    Greek Ray

    2012-09-01

    Full Text Available Abstract Background The concept of conserved processes presents unique opportunities for using nonhuman animal models in biomedical research. However, the concept must be examined in the context that humans and nonhuman animals are evolved, complex, adaptive systems. Given that nonhuman animals are examples of living systems that are differently complex from humans, what does the existence of a conserved gene or process imply for inter-species extrapolation? Methods We surveyed the literature including philosophy of science, biological complexity, conserved processes, evolutionary biology, comparative medicine, anti-neoplastic agents, inhalational anesthetics, and drug development journals in order to determine the value of nonhuman animal models when studying conserved processes. Results Evolution through natural selection has employed components and processes both to produce the same outcomes among species but also to generate different functions and traits. Many genes and processes are conserved, but new combinations of these processes or different regulation of the genes involved in these processes have resulted in unique organisms. Further, there is a hierarchy of organization in complex living systems. At some levels, the components are simple systems that can be analyzed by mathematics or the physical sciences, while at other levels the system cannot be fully analyzed by reducing it to a physical system. The study of complex living systems must alternate between focusing on the parts and examining the intact whole organism while taking into account the connections between the two. Systems biology aims for this holism. We examined the actions of inhalational anesthetic agents and anti-neoplastic agents in order to address what the characteristics of complex living systems imply for inter-species extrapolation of traits and responses related to conserved processes. Conclusion We conclude that even the presence of conserved processes is

  10. Animal models and conserved processes.

    Science.gov (United States)

    Greek, Ray; Rice, Mark J

    2012-09-10

    The concept of conserved processes presents unique opportunities for using nonhuman animal models in biomedical research. However, the concept must be examined in the context that humans and nonhuman animals are evolved, complex, adaptive systems. Given that nonhuman animals are examples of living systems that are differently complex from humans, what does the existence of a conserved gene or process imply for inter-species extrapolation? We surveyed the literature including philosophy of science, biological complexity, conserved processes, evolutionary biology, comparative medicine, anti-neoplastic agents, inhalational anesthetics, and drug development journals in order to determine the value of nonhuman animal models when studying conserved processes. Evolution through natural selection has employed components and processes both to produce the same outcomes among species but also to generate different functions and traits. Many genes and processes are conserved, but new combinations of these processes or different regulation of the genes involved in these processes have resulted in unique organisms. Further, there is a hierarchy of organization in complex living systems. At some levels, the components are simple systems that can be analyzed by mathematics or the physical sciences, while at other levels the system cannot be fully analyzed by reducing it to a physical system. The study of complex living systems must alternate between focusing on the parts and examining the intact whole organism while taking into account the connections between the two. Systems biology aims for this holism. We examined the actions of inhalational anesthetic agents and anti-neoplastic agents in order to address what the characteristics of complex living systems imply for inter-species extrapolation of traits and responses related to conserved processes. We conclude that even the presence of conserved processes is insufficient for inter-species extrapolation when the trait or response

  11. Propensity of Withania somnifera to Attenuate Behavioural, Biochemical, and Histological Alterations in Experimental Model of Stroke.

    Science.gov (United States)

    Sood, Abhilasha; Kumar, Aditya; Dhawan, Devinder K; Sandhir, Rajat

    2016-10-01

    The present study was designed to evaluate the beneficial effects of Withania somnifera (WS) pre-supplementation on middle cerebral artery occlusion (MCAO) model of ischemic stroke. Ischemic stroke was induced in the rats by inserting intraluminal suture for 90 min, followed by reperfusion injury for 24 h. The animals were assessed for locomotor functions (by neurological deficit scores, narrow beam walk and rotarod test), cognitive and anxiety-like behavioural functions (by morris water maze and elevated plus maze test). MCAO animals showed significant impairment in locomotor and cognitive functions. Neurobehavioural changes were accompanied by decreased acetylcholinesterase activity, increased oxidative stress in terms of enhanced lipid peroxidation and lowered thiol levels in the MCAO animals. In addition, MCAO animals had cerebral infarcts and the presence of pycnotic nuclei. Single-photon emission computerized tomography (SPECT) of MCAO animals revealed a cerebral infarct as a hypoactive area. On the other hand, pre-supplementation with WS (300 mg/kg body weight) for 30 days to MCAO animals was effective in restoring the acetylcholinesterase activity, lipid peroxidation, thiols and attenuated MCAO induced behavioural deficits. WS significantly reduced the cerebral infarct volume and ameliorated histopathological alterations. Improved blood flow was observed in the SPECT images from the brain regions of ischemic rats pre-treated with WS. The results of the study showed a protective effect of WS supplementation in ischemic stroke and are suggestive of its potential application in stroke management.

  12. A New Model for Secondary Prevention of Stroke: TRAnsition Coaching for Stroke (TRACS

    Directory of Open Access Journals (Sweden)

    Cheryl eBushnell

    2014-10-01

    Full Text Available Non-adherence to stroke prevention medications is a risk factor for first-ever and recurrent stroke. As of yet, there are no guidelines for processes to recognize and address medication non-adherence in stroke patients. We developed a new model of post-discharge prevention care that measures and addresses medication-taking (TRAnsition Coaching for Stroke or TRACS. TRACS includes personalized education about risk factors and medications prior to discharge, follow-up telephone calls, and appointments with a stroke nurse practitioner (NP. The stroke NP asks about medication use (persistence and whether doses are missed (adherence, and helps to solve problems with access to medications or side effects. In an analysis of 142 patients enrolled in TRACS from October 2012 to February 2014, medication persistence (use of medications from discharge to the time of measurement was about 80%. Medication persistence at NP visit was higher in those patients with a first-ever stroke (78.9 % vs those with recurrent stroke (60.7 %; p=0.045. Concerted efforts with 2-day RN follow-up calls and earlier NP appointments to improve medication-taking behaviors are underway.

  13. Parathyroid diseases and animal models.

    Science.gov (United States)

    Imanishi, Yasuo; Nagata, Yuki; Inaba, Masaaki

    2012-01-01

    CIRCULATING CALCIUM AND PHOSPHATE ARE TIGHTLY REGULATED BY THREE HORMONES: the active form of vitamin D (1,25-dihydroxyvitamin D), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). PTH acts to stimulate a rapid increment in serum calcium and has a crucial role in calcium homeostasis. Major target organs of PTH are kidney and bone. The oversecretion of the hormone results in hypercalcemia, caused by increased intestinal calcium absorption, reduced renal calcium clearance, and mobilization of calcium from bone in primary hyperparathyroidism. In chronic kidney disease, secondary hyperparathyroidism of uremia is observed in its early stages, and this finally develops into the autonomous secretion of PTH during maintenance hemodialysis. Receptors in parathyroid cells, such as the calcium-sensing receptor, vitamin D receptor, and FGF receptor (FGFR)-Klotho complex have crucial roles in the regulation of PTH secretion. Genes such as Cyclin D1, RET, MEN1, HRPT2, and CDKN1B have been identified in parathyroid diseases. Genetically engineered animals with these receptors and the associated genes have provided us with valuable information on the patho-physiology of parathyroid diseases. The application of these animal models is significant for the development of new therapies.

  14. Parathyroid diseases and animal models

    Directory of Open Access Journals (Sweden)

    Yasuo eImanishi

    2012-06-01

    Full Text Available Circulating calcium and phosphate are tightly regulated by 3 hormones: the active form of vitamin D (1,25-dihydroxyvitamin D, fibroblast growth factor (FGF-23, and parathyroid hormone (PTH. PTH acts to stimulate a rapid increment in serum calcium and has a crucial role in calcium homeostasis. Major target organs of PTH are kidney and bone. The oversecretion of the hormone results in hypercalcemia, caused by increased intestinal calcium absorption, reduced renal calcium clearance, and mobilization of calcium from bone in primary hyperparathyroidism. In chronic kidney disease, secondary hyperparathyroidism of uremia is observed in its early stages, and early stages, and this finally develops into the autonomous secretion of PTH during maintenance hemodialysis. Receptors in parathyroid cells, such as the calcium-sensing receptor, vitamin D receptor, and FGF receptor (FGFR-Klotho complex have crucial roles in the regulation of PTH secretion. Genes such as Cyclin D1, RET, MEN1, HRPT2, and CDKN1B have been identified in parathyroid diseases. Genetically engineered animals with these receptors and the associated genes have provided us with valuable information on the patho-physiology of parathyroid diseases. The application of these animal models is significant for the development of new therapies.

  15. Animal models for cancer cachexia.

    Science.gov (United States)

    Ballarò, Riccardo; Costelli, Paola; Penna, Fabio

    2016-12-01

    Cancer cachexia is a frequent syndrome that affects patient quality of life, anticancer treatment effectiveness, and overall survival. The lack of anticancer cachexia therapies likely relies on the complexity of the syndrome that renders difficult to design appropriate clinical trials and, conversely, on the insufficient knowledge of the underlying pathogenetic mechanisms. The aim of this review is to collect the most relevant latest information regarding cancer cachexia with a special focus on the experimental systems adopted for modeling the disease in translational studies. The scenario of preclinical models for the study of cancer cachexia is not static and is rapidly evolving in parallel with new prospective treatment options. The well established syngeneic models using rodent cancer cells injected ectopically are now used alongside new ones featuring orthotopic injection, human cancer cell or patient-derived xenograft, or spontaneous tumors in genetically engineered mice. The use of more complex animal models that better resemble cancer cachexia, ideally including also the administration of chemotherapy, will expand the understanding of the underlying mechanisms and will allow a more reliable evaluation of prospective drugs for translational purposes.

  16. Efficacy of Alteplase in a Mouse Model of Acute Ischemic Stroke: A Retrospective Pooled Analysis.

    Science.gov (United States)

    Orset, Cyrille; Haelewyn, Benoit; Allan, Stuart M; Ansar, Saema; Campos, Francesco; Cho, Tae Hee; Durand, Anne; El Amki, Mohamad; Fatar, Marc; Garcia-Yébenes, Isaac; Gauberti, Maxime; Grudzenski, Saskia; Lizasoain, Ignacio; Lo, Eng; Macrez, Richard; Margaill, Isabelle; Maysami, Samaneh; Meairs, Stephen; Nighoghossian, Norbert; Orbe, Josune; Paramo, Jose Antonio; Parienti, Jean-Jacques; Rothwell, Nancy J; Rubio, Marina; Waeber, Christian; Young, Alan R; Touzé, Emmanuel; Vivien, Denis

    2016-05-01

    The debate over the fact that experimental drugs proposed for the treatment of stroke fail in the translation to the clinical situation has attracted considerable attention in the literature. In this context, we present a retrospective pooled analysis of a large data set from preclinical studies, to examine the effects of early versus late administration of intravenous recombinant tissue-type plasminogen activator. We collected data from 26 individual studies from 9 international centers (13 researchers; 716 animals) that compared recombinant tissue-type plasminogen activator with controls, in a unique mouse model of thromboembolic stroke induced by an in situ injection of thrombin into the middle cerebral artery. Studies were classified into early (stroke in mice. The power analysis reveals that a multicenter trial would require 123 animals per group instead of 40 for a single-center trial. © 2016 American Heart Association, Inc.

  17. Chronobiology of ethanol: animal models.

    Science.gov (United States)

    Rosenwasser, Alan M

    2015-06-01

    Clinical and epidemiological observations have revealed that alcohol abuse and alcoholism are associated with widespread disruptions in sleep and other circadian biological rhythms. As with other psychiatric disorders, animal models have been very useful in efforts to better understand the cause and effect relationships underlying the largely correlative human data. This review summarizes the experimental findings indicating bidirectional interactions between alcohol (ethanol) consumption and the circadian timing system, emphasizing behavioral studies conducted in the author's laboratory. Together with convergent evidence from multiple laboratories, the work summarized here establishes that ethanol intake (or administration) alters fundamental properties of the underlying circadian pacemaker. In turn, circadian disruption induced by either environmental or genetic manipulations can alter voluntary ethanol intake. These reciprocal interactions may create a vicious cycle that contributes to the downward spiral of alcohol and drug addiction. In the future, such studies may lead to the development of chronobiologically based interventions to prevent relapse and effectively mitigate some of the societal burden associated with such disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Animal Robot Assisted-therapy for Rehabilitation of Patient with Post-Stroke Depression

    Science.gov (United States)

    Zikril Zulkifli, Winal; Shamsuddin, Syamimi; Hwee, Lim Thiam

    2017-06-01

    Recently, the utilization of therapeutic animal robots has expanded. This research aims to explore robotics application for mental healthcare in Malaysia through human-robot interaction (HRI). PARO, the robotic seal PARO was developed to give psychological effects on humans. Major Depressive Disorder (MDD) is a common but severe mood disorder. This study focuses on the interaction protocol between PARO and patients with MDD. Initially, twelve rehabilitation patients gave subjective evaluation on their first interaction with PARO. Next, therapeutic interaction environment was set-up with PARO in it to act as an augmentation strategy with other psychological interventions for post-stroke depression. Patient was exposed to PARO for 20 minutes. The results of behavioural analysis complemented with information from HRI survey question. The analysis also observed that the individual interactors engaged with the robot in diverse ways based on their needs Results show positive reaction toward the acceptance of an animal robot. Next, therapeutic interaction is set-up for PARO to contribute as an augmentation strategy with other psychological interventions for post-stroke depression. The outcome is to reduce the stress level among patients through facilitated therapy session with PARO

  19. Stroke

    Science.gov (United States)

    ... adjust your treatment as needed. Rehabilitation After a stroke, you may need rehabilitation (rehab) to help you recover. Rehab may include working with speech, physical, and occupational therapists. Language, ... may have trouble communicating after a stroke. You may not be able to find the ...

  20. A working model of stroke recovery from rehabilitation robotics practitioners.

    Science.gov (United States)

    Krebs, Hermano Igo; Volpe, Bruce; Hogan, Neville

    2009-02-25

    We reviewed some of our initial insights about the process of upper-limb behavioral recovery following stroke. Evidence to date indicates that intensity, task specificity, active engagement, and focusing training on motor coordination are key factors enabling efficacious recovery. On modeling, experience with over 400 stroke patients has suggested a working model of recovery similar to implicit motor learning. Ultimately, we plan to apply these insights in the development of customized training paradigms to enhance recovery.

  1. Towards a reliable animal model of migraine

    DEFF Research Database (Denmark)

    Olesen, Jes; Jansen-Olesen, Inger

    2012-01-01

    The pharmaceutical industry shows a decreasing interest in the development of drugs for migraine. One of the reasons for this could be the lack of reliable animal models for studying the effect of acute and prophylactic migraine drugs. The infusion of glyceryl trinitrate (GTN) is the best validated...... and most studied human migraine model. Several attempts have been made to transfer this model to animals. The different variants of this model are discussed as well as other recent models....

  2. Animal models in fetal medicine and obstetrics

    DEFF Research Database (Denmark)

    Dahl Andersen, Maria; Alstrup, Aage Kristian Olsen; Duvald, Christina Søndergaard

    2017-01-01

    Animal models remain essential to understand the fundamental mechanisms occurring in fetal medicine and obstetric diseases, such as intrauterine growth restriction, preeclampsia and gestational diabetes. These vary regarding the employed method used for induction of the disease, and vary regarding...... the animal characteristics (size, number of fetuses, placenta barrier type, etc). While none of these exactly mirrors the human condition, different pregnant animal models (mice, rats, guinea pigs, chinchillas, rabbits, sheep and pigs) are here described with respect to advantages and limitations...

  3. Animal models of cerebral arterial gas embolism

    NARCIS (Netherlands)

    Weenink, Robert P.; Hollmann, Markus W.; van Hulst, Robert A.

    2012-01-01

    Cerebral arterial gas embolism is a dreaded complication of diving and invasive medical procedures. Many different animal models have been used in research on cerebral arterial gas embolism. This review provides an overview of the most important characteristics of these animal models. The properties

  4. 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.

  5. 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

  6. Animal model and neurobiology of suicide.

    Science.gov (United States)

    Preti, Antonio

    2011-06-01

    Animal models are formidable tools to investigate the etiology, the course and the potential treatment of an illness. No convincing animal model of suicide has been produced to date, and despite the intensive study of thousands of animal species naturalists have not identified suicide in nonhuman species in field situations. When modeling suicidal behavior in the animal, the greatest challenge is reproducing the role of will and intention in suicide mechanics. To overcome this limitation, current investigations on animals focus on every single step leading to suicide in humans. The most promising endophenotypes worth investigating in animals are the cortisol social-stress response and the aggression/impulsivity trait, involving the serotonergic system. Astroglia, neurotrophic factors and neurotrophins are implied in suicide, too. The prevention of suicide rests on the identification and treatment of every element increasing the risk. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Animal Migraine Models for Drug Development

    DEFF Research Database (Denmark)

    Jansen-Olesen, Inger; Tfelt-Hansen, Peer; Olesen, Jes

    2013-01-01

    responses are likely to be behavioral, allowing multiple experiments in each individual animal. Distinction is made between acute and prophylactic models and how to validate each of them. Modern insight into neurobiological mechanisms of migraine is so good that it is only a question of resources...... for headache has almost come to a standstill partly because of a lack of valid animal models. Here we review previous models with emphasis on optimal characteristics of a future model. In addition to selection of animal species, the method of induction of migraine-like changes and the method of recording...

  8. Overview of Animal Models of Obesity

    Science.gov (United States)

    Lutz, Thomas A.; Woods, Stephen C.

    2012-01-01

    This is a review of animal models of obesity currently used in research. We have focused upon more commonly utilized models since there are far too many newly created models to consider, especially those caused by selective molecular genetic approaches modifying one or more genes in specific populations of cells. Further, we will not discuss the generation and use of inducible transgenic animals (induced knock-out or knock-in) even though they often bear significant advantages compared to traditional transgenic animals; influences of the genetic modification during the development of the animals can be minimized. The number of these animal models is simply too large to be covered in this chapter. PMID:22948848

  9. Spontaneous ischaemic stroke lesions in a dog brain: neuropathological characterisation and comparison to human ischaemic stroke

    DEFF Research Database (Denmark)

    Thomsen, Barbara Blicher; Gredal, Hanne; Wirenfeldt, Martin

    2017-01-01

    Background Dogs develop spontaneous ischaemic stroke with a clinical picture closely resembling human ischaemic stroke patients. Animal stroke models have been developed, but it has proved difficult to translate results obtained from such models into successful therapeutic strategies in human....../macrophages and astrocytes. Conclusions The neuropathological changes reported in the present study were similar to findings in human patients with ischaemic stroke. The dog with spontaneous ischaemic stroke is of interest as a complementary spontaneous animal model for further neuropathological studies....... stroke patients. In order to face this apparent translational gap within stroke research, dogs with ischaemic stroke constitute an opportunity to study the neuropathology of ischaemic stroke in an animal species. Case presentation A 7 years and 8 months old female neutered Rottweiler dog suffered...

  10. Animal models of obesity and diabetes mellitus

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Clemmensen, Christoffer; Hofmann, Susanna M

    2018-01-01

    More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover...... available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models....

  11. The WZNW model on PSU(1, 1 vertical stroke 2)

    Energy Technology Data Exchange (ETDEWEB)

    Goetz, G. [CEA Centre d' Etudes de Saclay, 91 - Gif-sur-Yvette (France). Service de Physique Theorique; Quella, T. [King' s College London (United Kingdom). Dept. of Mathematics]|[Amsterdam Univ. (Netherlands). KdV Institute for Mathematics; Schomerus, V. [CEA Centre d' Etudes de Saclay, 91 - Gif-sur-Yvette (France). Service de Physique Theorique]|[Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2006-10-15

    According to the work of Berkovits, Vafa and Witten, the non-linear sigma model on the supergroup PSU(1,1 vertical stroke 2) is the essential building block for string theory on AdS{sub 3}xS{sup 3}xT{sup 4}. Models associated with a non-vanishing value of the RR flux can be obtained through a psu(1,1 vertical stroke 2) invariant marginal deformation of the WZNW model on PSU(1,1 vertical stroke 2). We take this as a motivation to present a manifestly psu(1,1 vertical stroke 2) covariant construction of the model at the Wess-Zumino point, corresponding to a purely NSNS background 3-form flux. At this point the model possesses an enhanced psu(1,1 vertical stroke 2) current algebra symmetry whose representation theory, including explicit character formulas, is developed systematically in the first part of the paper. The space of vertex operators and a free fermion representation for their correlation functions is our main subject in the second part. Contrary to a widespread claim, bosonic and fermionic fields are necessarily coupled to each other. The interaction changes the supersymmetry transformations, with drastic consequences for the multiplets of localized normalizable states in the model. It is only this fact which allows us to decompose the full state space into multiplets of the global supersymmetry. We analyze these decompositions systematically as a preparation for a forthcoming study of the RR deformation. (orig.)

  12. The WZNW model on PSU(1, 1 vertical stroke 2)

    International Nuclear Information System (INIS)

    Goetz, G.

    2006-10-01

    According to the work of Berkovits, Vafa and Witten, the non-linear sigma model on the supergroup PSU(1,1 vertical stroke 2) is the essential building block for string theory on AdS 3 xS 3 xT 4 . Models associated with a non-vanishing value of the RR flux can be obtained through a psu(1,1 vertical stroke 2) invariant marginal deformation of the WZNW model on PSU(1,1 vertical stroke 2). We take this as a motivation to present a manifestly psu(1,1 vertical stroke 2) covariant construction of the model at the Wess-Zumino point, corresponding to a purely NSNS background 3-form flux. At this point the model possesses an enhanced psu(1,1 vertical stroke 2) current algebra symmetry whose representation theory, including explicit character formulas, is developed systematically in the first part of the paper. The space of vertex operators and a free fermion representation for their correlation functions is our main subject in the second part. Contrary to a widespread claim, bosonic and fermionic fields are necessarily coupled to each other. The interaction changes the supersymmetry transformations, with drastic consequences for the multiplets of localized normalizable states in the model. It is only this fact which allows us to decompose the full state space into multiplets of the global supersymmetry. We analyze these decompositions systematically as a preparation for a forthcoming study of the RR deformation. (orig.)

  13. Brain repair after stroke--a novel neurological model.

    Science.gov (United States)

    Small, Steven L; Buccino, Giovanni; Solodkin, Ana

    2013-12-01

    Following stroke, patients are commonly left with debilitating motor and speech impairments. This article reviews the state of the art in neurological repair for stroke and proposes a new model for the future. We suggest that stroke treatment--from the time of the ictus itself to living with the consequences--must be fundamentally neurological, from limiting the extent of injury at the outset, to repairing the consequent damage. Our model links brain and behaviour by targeting brain circuits, and we illustrate the model though action observation treatment, which aims to enhance brain network connectivity. The model is based on the assumptions that the mechanisms of neural repair inherently involve cellular and circuit plasticity, that brain plasticity is a synaptic phenomenon that is largely stimulus-dependent, and that brain repair required both physical and behavioural interventions that are tailored to reorganize specific brain circuits. We review current approaches to brain repair after stroke and present our new model, and discuss the biological foundations, rationales, and data to support our novel approach to upper-extremity and language rehabilitation. We believe that by enhancing plasticity at the level of brain network interactions, this neurological model for brain repair could ultimately lead to a cure for stroke.

  14. Animal Models of Middle Ear Cholesteatoma

    Directory of Open Access Journals (Sweden)

    Tomomi Yamamoto-Fukuda

    2011-01-01

    Full Text Available Middle ear acquired cholesteatoma is a pathological condition associated with otitis media, which may be associated with temporal bone resorption, otorrhea and hearing loss, and occasionally various other complications. Cholesteatoma is characterized by the enhanced proliferation of epithelial cells with aberrant morphologic characteristics. Unfortunately, our understanding of the mechanism underlying its pathogenesis is limited. To investigate its pathogenesis, different animal models have been used. This paper provides a brief overview of the current status of research in the field of pathogenesis of middle ear acquired cholesteatoma, four types of animal models previously reported on, up-to-date cholesteatoma research using these animal models, our current studies of the local hybrid ear model, and the future prospect of new animal models of middle ear cholesteatoma.

  15. Animal models: an important tool in mycology.

    Science.gov (United States)

    Capilla, Javier; Clemons, Karl V; Stevens, David A

    2007-12-01

    Animal models of fungal infections are, and will remain, a key tool in the advancement of the medical mycology. Many different types of animal models of fungal infection have been developed, with murine models the most frequently used, for studies of pathogenesis, virulence, immunology, diagnosis, and therapy. The ability to control numerous variables in performing the model allows us to mimic human disease states and quantitatively monitor the course of the disease. However, no single model can answer all questions and different animal species or different routes of infection can show somewhat different results. Thus, the choice of which animal model to use must be made carefully, addressing issues of the type of human disease to mimic, the parameters to follow and collection of the appropriate data to answer those questions being asked. This review addresses a variety of uses for animal models in medical mycology. It focuses on the most clinically important diseases affecting humans and cites various examples of the different types of studies that have been performed. Overall, animal models of fungal infection will continue to be valuable tools in addressing questions concerning fungal infections and contribute to our deeper understanding of how these infections occur, progress and can be controlled and eliminated.

  16. The development of expertise: animal models?

    Science.gov (United States)

    Helton, William S

    2004-01-01

    There is a continuing debate in the psychological literature between researchers who lean more toward learning theories of expertise development and those who lean more toward talent theories. However, the development of human expertise has not been open to direct experimental methods and will probably continue to elude experimentalists in the future. A promising alternative to direct experimental methods is to use human animal models, a possibility that researchers in expertise seem to have overlooked. However, there are studies in the animal behavior literature that address the development of nonhuman animal expertise without specifically referring to the topic as expertise. In the present study, the author discusses two nonhuman animal examples of expertise development that have been researched by ethologists. Nonhuman animal expertise development, unlike human expertise development, is subject to direct experimentation. The author thus recommends that researchers use nonhuman animals in their studies of expertise.

  17. Animal Models of Chemotherapy-induced Mucositis

    DEFF Research Database (Denmark)

    Sangild, Per T; Shen, René Liang; Pontoppidan, Peter Erik Lotko

    2018-01-01

    of CIM, and how to prevent it. Animal models allow highly controlled experimental conditions, detailed organ (e.g. GIT) insights, standardized, clinically-relevant treatment regimens and discovery of new biomarkers. Still, surprisingly few results from animal models have been translated into clinical CIM......Chemotherapy for cancer patients induces damaging tissue reactions along the epithelium of the gastrointestinal tract (GIT). This chemotherapy-induced mucositis (CIM) is a serious side effect of cytotoxic drugs and several animal models of CIM have been developed to help understand the progression...... mangement and treatments. The results obtained from specific animal models can be difficult to translate to the diverse range of CIM manifestations in patients that vary according to the antineoplastic drugs, dose, underlying (cancer) disease and patient characteristics (e.g. age, genetics, body...

  18. Lessons from animal models of osteoarthritis.

    NARCIS (Netherlands)

    Berg, W.B. van den

    2008-01-01

    Animal models of osteoarthritis (OA) provide valuable insight into pathogenetic pathways. Although OA is not an inflammatory disease, synovial activation clearly plays a role. Matrix metalloproteinases 3 (stromelysin) and 13 (collagenase) appear crucial, and a disintegrin and metalloproteinase with

  19. STRESS RESPONSE STUDIES USING ANIMAL MODELS

    Science.gov (United States)

    This presentation will provide the evidence that ozone exposure in animal models induce neuroendocrine stress response and this stress response modulates lung injury and inflammation through adrenergic and glucocorticoid receptors.

  20. Animal models of cerebral amyloid angiopathy.

    Science.gov (United States)

    Jäkel, Lieke; Van Nostrand, William E; Nicoll, James A R; Werring, David J; Verbeek, Marcel M

    2017-10-15

    Cerebral amyloid angiopathy (CAA), due to vascular amyloid β (Aβ) deposition, is a risk factor for intracerebral haemorrhage and dementia. CAA can occur in sporadic or rare hereditary forms, and is almost invariably associated with Alzheimer's disease (AD). Experimental (animal) models are of great interest in studying mechanisms and potential treatments for CAA. Naturally occurring animal models of CAA exist, including cats, dogs and non-human primates, which can be used for longitudinal studies. However, due to ethical considerations and low throughput of these models, other animal models are more favourable for research. In the past two decades, a variety of transgenic mouse models expressing the human Aβ precursor protein (APP) has been developed. Many of these mouse models develop CAA in addition to senile plaques, whereas some of these models were generated specifically to study CAA. In addition, other animal models make use of a second stimulus, such as hypoperfusion or hyperhomocysteinemia (HHcy), to accelerate CAA. In this manuscript, we provide a comprehensive review of existing animal models for CAA, which can aid in understanding the pathophysiology of CAA and explore the response to potential therapies. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  1. Characterization of ICP Behavior in an Experimental Model of Hemorrhagic Stroke in Rats.

    Science.gov (United States)

    Cardim, Danilo Augusto; do Val da Silva, Raquel Araújo; Cardim, Ana Carolina; Cabella, Brenno Caetano Troca; Frigieri, Gustavo Henrique; de Sousa Torres, Cecília Vidal; Wang, Charles Chenwei; de Pacheco Andrade, Rodrigo Albuquerque; Scandiuzzi, Renata Caldo; Rizzatti, Ana Carolina Segato; Mascarenhas, Yvonne Maria; Leite, João Pereira; Mascarenhas, Sérgio

    2016-01-01

    Intracranial pressure (ICP) monitoring is sometimes required in clinical pictures of stroke, as extensive intraparenchymal hematomas and intracranial bleeding may severely increase ICP, which can lead to irreversible conditions, such as dementia and cognitive derangement. ICP monitoring has been accepted as a procedure for the safe diagnosis of increased ICP, and for the treatment of intracranial hypertension in some diseases. In this work, we evaluated ICP behavior during the induction of an experimental model of autologous blood injection in rats, simulating a hemorrhagic stroke. Rats were subjected to stereotactic surgery for the implantation of a unilateral cannula into the left striatal region of the brain. Autologous blood was infused into the left striatal region with an automatic microinfusion pump. ICP monitoring was performed throughout the procedure of hemorrhagic stroke induction. Analyses consisted of short-time Fourier transform for ICP before and after stroke induction and the histological processing of the animals' brains. Short-time Fourier transform analysis demonstrated oscillations in the ICP frequency components throughout time after the microinjections compared with data before them. Histological analysis revealed neuropathological changes in the striatum in all microinjected animals.

  2. A cognitive model's view of animal cognition

    Directory of Open Access Journals (Sweden)

    Sidney D'MELLO, Stan FRANKLIN

    2011-08-01

    Full Text Available Although it is a relatively new field of study, the animal cognition literature is quite extensive and difficult to synthesize. This paper explores the contributions a comprehensive, computational, cognitive model can make toward organizing and assimilating this literature, as well as toward identifying important concepts and their interrelations. Using the LIDA model as an example, a framework is described within which to integrate the diverse research in animal cognition. Such a framework can provide both an ontology of concepts and their relations, and a working model of an animal’s cognitive processes that can compliment active empirical research. In addition to helping to account for a broad range of cognitive processes, such a model can help to comparatively assess the cognitive capabilities of different animal species. After deriving an ontology for animal cognition from the LIDA model, we apply it to develop the beginnings of a database that maps the cognitive facilities of a variety of animal species. We conclude by discussing future avenues of research, particularly the use of computational models of animal cognition as valuable tools for hypotheses generation and testing [Current Zoology 57 (4: 499–513, 2011].

  3. Animal models in motion sickness research

    Science.gov (United States)

    Daunton, Nancy G.

    1990-01-01

    Practical information on candidate animal models for motion sickness research and on methods used to elicit and detect motion sickness in these models is provided. Four good potential models for use in motion sickness experiments include the dog, cat, squirrel monkey, and rat. It is concluded that the appropriate use of the animal models, combined with exploitation of state-of-the-art biomedical techniques, should generate a great step forward in the understanding of motion sickness mechanisms and in the development of efficient and effective approaches to its prevention and treatment in humans.

  4. Gait analysis in a pre- and post-ischemic stroke biomedical pig model.

    Science.gov (United States)

    Duberstein, Kylee Jo; Platt, Simon R; Holmes, Shannon P; Dove, C Robert; Howerth, Elizabeth W; Kent, Marc; Stice, Steven L; Hill, William D; Hess, David C; West, Franklin D

    2014-02-10

    Severity of neural injury including stroke in human patients, as well as recovery from injury, can be assessed through changes in gait patterns of affected individuals. Similar quantification of motor function deficits has been measured in rodent animal models of such injuries. However, due to differences in fundamental structure of human and rodent brains, there is a need to develop a large animal model to facilitate treatment development for neurological conditions. Porcine brain structure is similar to that of humans, and therefore the pig may make a more clinically relevant animal model. The current study was undertaken to determine key gait characteristics in normal biomedical miniature pigs and dynamic changes that occur post-neural injury in a porcine middle cerebral artery (MCA) occlusion ischemic stroke model. Yucatan miniature pigs were trained to walk through a semi-circular track and were recorded with high speed cameras to detect changes in key gait parameters. Analysis of normal pigs showed overall symmetry in hindlimb swing and stance times, forelimb stance time, along with step length, step velocity, and maximum hoof height on both fore and hindlimbs. A subset of pigs were again recorded at 7, 5 and 3 days prior to MCA occlusion and then at 1, 3, 5, 7, 14 and 30 days following surgery. MRI analysis showed that MCA occlusion resulted in significant infarction. Gait analysis indicated that stroke resulted in notable asymmetries in both temporal and spatial variables. Pigs exhibited lower maximum front hoof height on the paretic side, as well as shorter swing time and longer stance time on the paretic hindlimb. These results support that gait analysis of stroke injury is a highly sensitive detection method for changes in gait parameters in pig. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Final model of multicriterionevaluation of animal welfare

    DEFF Research Database (Denmark)

    Bonde, Marianne; Botreau, R; Bracke, MBM

    One major objective of Welfare Quality® is to propose harmonized methods for the overall assessment of animal welfare on farm and at slaughter that are science based and meet societal concerns. Welfare is a multidimensional concept and its assessment requires measures of different aspects. Welfare...... Quality® proposes a formal evaluation model whereby the data on animals or their environment are transformed into value scores that reflect compliance with 12 subcriteria and 4 criteria of good welfare. Each animal unit is then allocated to one of four categories: excellent welfare, enhanced welfare......, acceptable welfare and not classified. This evaluation model is tuned according to the views of experts from animal and social sciences, and stakeholders....

  6. Societal value of stem cell therapy in stroke--a modeling study.

    Science.gov (United States)

    Svensson, Johanna; Ghatnekar, Ola; Lindgren, Arne; Lindvall, Olle; Norrving, Bo; Persson, Ulf; Kokaia, Zaal

    2012-01-01

    Stroke is one of the major causes of disability in the adult population and represents a heavy social and economic burden. Currently available therapeutic tools to support the recovery of impaired brain functions are quite limited. Animal studies have demonstrated that neuronal replacement and partial reconstruction of neural circuitry or modulation of the recovery process is possible with cell transplantation in the damaged adult brain. Stem cell therapy (SCT) may promote functional recovery also in stroke patients, thereby improving quality of life and reducing costs. Our aim was to estimate the potential societal value of SCT in stroke patients. We created a decision-analytic model in Microsoft Excel 2010 to assess life-long costs and quality-adjusted life years (QALYs) of SCT versus standard care for stroke patients from a societal perspective. The model structure consisted of 7 health states in accordance with the modified Rankin Scale (mRS). We modeled for age (55, 65, and 75 years), functional status at discharge (mRS 2, 3, and 4), effectiveness of SCT (50 and 25% increase in the probability to improve 1 mRS grade), mode of stem cell administration, risk of recurrent stroke, complications of intervention, and use of immunosuppressive drugs. The difference between an assumed societal willingness to pay for a QALY gain in Sweden (110,400 USD) and the cost per QALY gain resulting from the model was interpreted as the value of SCT. Increased survival (1.06 life years) and improved functional status gave rise to an estimated gain of 1.34 QALY in a cohort of patients aged 55 with mRS 2 at hospital discharge. Although the SCT intervention increased costs by 64,014 USD (excluding cost of stem cells), the costs of intervention were offset mainly by decreased productivity losses. In total, the intervention saved 19,055 USD, i.e., at a price of 19,055 USD for stem cells, the SCT would be cost neutral. The societal value of SCT was 166,500 USD. The application of the

  7. Optogenetics in animal model of alcohol addiction

    Science.gov (United States)

    Nalberczak, Maria; Radwanska, Kasia

    2014-11-01

    Our understanding of the neuronal and molecular basis of alcohol addiction is still not satisfactory. As a consequence we still miss successful therapy of alcoholism. One of the reasons for such state is the lack of appropriate animal models which would allow in-depth analysis of biological basis of addiction. Here we will present our efforts to create the animal model of alcohol addiction in the automated learning device, the IntelliCage setup. Applying this model to optogenetically modified mice with remotely controlled regulation of selected neuronal populations by light may lead to very precise identification of neuronal circuits involved in coding addiction-related behaviors.

  8. Oxymetazoline ototoxicity in a chinchilla animal model.

    Science.gov (United States)

    Daniel, Sam J; Akinpelu, Olubunmi V; Sahmkow, Sofia; Funnell, W Robert J; Akache, Fadi

    2012-01-01

    To investigate possible ototoxic effects of a one-time application of oxymetazoline drops in a chinchilla animal model with tympanostomy tubes. Study Design. A prospective, controlled animal study. The Research Institute of the Montreal's Children Hospital, McGill University Health Centre. Ventilation tubes were inserted in both ears of 12 animals. One ear was randomly assigned to receive oxymetazoline drops (0.5 mL). The contralateral ear did not receive any drops, serving as a control ear. Distortion product otoacoustic emissions were measured bilaterally for a wide range of frequencies (between 1 and 16 kHz) before and 1 day after the application of oxymetazoline in the experimental ears. Two months later, the animals were sacrificed and all cochleae were dissected out and processed for scanning electron microscopy. In this established chinchilla animal model, the measured distortion product otoacoustic emission amplitudes and the morphological appearance on scanning electron microscopy were similar for both control and experimental ears. Oxymetazoline did not cause ototoxicity in a chinchilla animal model 2 months after a single application via a tympanostomy tube.

  9. Animal models of preeclampsia; uses and limitations.

    LENUS (Irish Health Repository)

    McCarthy, F P

    2012-01-31

    Preeclampsia remains a leading cause of maternal and fetal morbidity and mortality and has an unknown etiology. The limited progress made regarding new treatments to reduce the incidence and severity of preeclampsia has been attributed to the difficulties faced in the development of suitable animal models for the mechanistic research of this disease. In addition, animal models need hypotheses on which to be based and the slow development of testable hypotheses has also contributed to this poor progress. The past decade has seen significant advances in our understanding of preeclampsia and the development of viable reproducible animal models has contributed significantly to these advances. Although many of these models have features of preeclampsia, they are still poor overall models of the human disease and limited due to lack of reproducibility and because they do not include the complete spectrum of pathophysiological changes associated with preeclampsia. This review aims to provide a succinct and comprehensive assessment of current animal models of preeclampsia, their uses and limitations with particular attention paid to the best validated and most comprehensive models, in addition to those models which have been utilized to investigate potential therapeutic interventions for the treatment or prevention of preeclampsia.

  10. Animal models for HIV cure research

    Directory of Open Access Journals (Sweden)

    Ben Bruno Policicchio

    2016-01-01

    Full Text Available The HIV-1/AIDS pandemic continues to spread unabated worldwide and no vaccine exists within our grasp. Effective antiretroviral therapy (ART has been developed, but ART cannot clear the virus from the infected patient. A cure for HIV-1 is badly needed to stop both the spread of the virus in human populations and disease progression in infected individuals. A safe and effective cure strategy for HIV infection will require multiple tools and appropriate animal models are tools that are central to cure research. An ideal animal model should recapitulate the essential aspects of HIV pathogenesis and associated immune responses, while permitting invasive studies, thus allowing a thorough evaluation of strategies aimed at reducing the size of the reservoir (functional cure or eliminating the reservoir altogether (sterilizing cure. Since there is no perfect animal model for cure research, multiple models have been tailored and tested to address specific quintessential questions of virus persistence and eradication. The development of new nonhuman primate and mouse models, along with a certain interest in the feline model, have the potential to fuel cure research. In this review, we highlight the major animal models currently utilized for cure research and the contributions of each model to this goal.

  11. Animal Models for HIV Cure Research.

    Science.gov (United States)

    Policicchio, Benjamin B; Pandrea, Ivona; Apetrei, Cristian

    2016-01-01

    The HIV-1/AIDS pandemic continues to spread unabated worldwide, and no vaccine exists within our grasp. Effective antiretroviral therapy (ART) has been developed, but ART cannot clear the virus from the infected patient. A cure for HIV-1 is badly needed to stop both the spread of the virus in human populations and disease progression in infected individuals. A safe and effective cure strategy for human immunodeficiency virus (HIV) infection will require multiple tools, and appropriate animal models are tools that are central to cure research. An ideal animal model should recapitulate the essential aspects of HIV pathogenesis and associated immune responses, while permitting invasive studies, thus allowing a thorough evaluation of strategies aimed at reducing the size of the reservoir (functional cure) or eliminating the reservoir altogether (sterilizing cure). Since there is no perfect animal model for cure research, multiple models have been tailored and tested to address specific quintessential questions of virus persistence and eradication. The development of new non-human primate and mouse models, along with a certain interest in the feline model, has the potential to fuel cure research. In this review, we highlight the major animal models currently utilized for cure research and the contributions of each model to this goal.

  12. The role of sleep in recovery following ischemic stroke: A review of human and animal data

    OpenAIRE

    Duss, Simone B.; Seiler, Andrea; Schmidt, Markus H.; Pace, Marta; Adamantidis, Antoine; Müri, René M.; Bassetti, Claudio L.

    2016-01-01

    Despite advancements in understanding the pathophysiology of stroke and the state of the art in acute management of afflicted patients as well as in subsequent neurorehabilitation training, stroke remains the most common neurological cause of long-term disability in adulthood. To enhance stroke patients’ independence and well-being it is necessary, therefore, to consider and develop new therapeutic strategies and approaches. We postulate that sleep might play a pivotal role in neurorehabilita...

  13. Large animal models for stem cell therapy.

    Science.gov (United States)

    Harding, John; Roberts, R Michael; Mirochnitchenko, Oleg

    2013-03-28

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions

  14. Neuroprotective Properties and Mechanisms of Resveratrol in in Vitro and in Vivo Experimental Cerebral Stroke Models

    Science.gov (United States)

    2013-01-01

    Resveratrol, a natural stilbene present at relatively high concentrations in grape skin and seeds and red wine, is known for its purported antioxidant activity in the vascular and nervous systems. In contrast to its direct antioxidant role within the central nervous system, recent research supports a protective mechanism through increasing endogenous cellular antioxidant defenses, which triggers a cascade of parallel neuroprotective pathways. A growing body of in vitro and in vivo evidence indicates that resveratrol acts through multiple pathways and reduces ischemic damage in vital organs, such as the heart and the brain, in various rodent models. Most of the protective biological actions of resveratrol have been associated with its antioxidative, anti-inflammatory, and antiapoptotic properties and other indirect pathways. Continued public interest and increasing resveratrol supplements on the market warrant a review of the available in vitro and in vivo science reported in the stroke-related literature. Rigorous clinical trials evaluating the effects of resveratrol in stroke are absent, though the general population consumption appears to be relatively safe. Resveratrol has shown potential for treating stroke in laboratory animals and in vitro human cell studies, yet there is still a need for human research in preclinical settings. This review summarizes many of the findings on the neuroprotective potential of resveratrol in cerebral stroke, focusing on both the in vitro and in vivo experimental models and some proposed mechanisms of action. PMID:23758534

  15. Neuroprotective properties and mechanisms of resveratrol in in vitro and in vivo experimental cerebral stroke models.

    Science.gov (United States)

    Singh, Nilendra; Agrawal, Megha; Doré, Sylvain

    2013-08-21

    Resveratrol, a natural stilbene present at relatively high concentrations in grape skin and seeds and red wine, is known for its purported antioxidant activity in the vascular and nervous systems. In contrast to its direct antioxidant role within the central nervous system, recent research supports a protective mechanism through increasing endogenous cellular antioxidant defenses, which triggers a cascade of parallel neuroprotective pathways. A growing body of in vitro and in vivo evidence indicates that resveratrol acts through multiple pathways and reduces ischemic damage in vital organs, such as the heart and the brain, in various rodent models. Most of the protective biological actions of resveratrol have been associated with its antioxidative, anti-inflammatory, and antiapoptotic properties and other indirect pathways. Continued public interest and increasing resveratrol supplements on the market warrant a review of the available in vitro and in vivo science reported in the stroke-related literature. Rigorous clinical trials evaluating the effects of resveratrol in stroke are absent, though the general population consumption appears to be relatively safe. Resveratrol has shown potential for treating stroke in laboratory animals and in vitro human cell studies, yet there is still a need for human research in preclinical settings. This review summarizes many of the findings on the neuroprotective potential of resveratrol in cerebral stroke, focusing on both the in vitro and in vivo experimental models and some proposed mechanisms of action.

  16. Recognizing Strokes in Tennis Videos Using Hidden Markov Models

    NARCIS (Netherlands)

    Petkovic, M.; Jonker, Willem; Zivkovic, Z.

    This paper addresses content-based video retrieval with an emphasis on recognizing events in tennis game videos. In particular, we aim at recognizing different classes of tennis strokes using automatic learning capability of Hidden Markov Models. Driven by our domain knowledge, a robust player

  17. Standardization of A Physiologic Hypoparathyroidism Animal Model.

    Science.gov (United States)

    Jung, Soo Yeon; Kim, Ha Yeong; Park, Hae Sang; Yin, Xiang Yun; Chung, Sung Min; Kim, Han Su

    2016-01-01

    Ideal hypoparathyroidism animal models are a prerequisite to developing new treatment modalities for this disorder. The purpose of this study was to evaluate the feasibility of a model whereby rats were parathyroidectomized (PTX) using a fluorescent-identification method and the ideal calcium content of the diet was determined. Thirty male rats were divided into surgical sham (SHAM, n = 5) and PTX plus 0, 0.5, and 2% calcium diet groups (PTX-FC (n = 5), PTX-NC (n = 10), and PTX-HC (n = 10), respectively). Serum parathyroid hormone levels decreased to non-detectable levels in all PTX groups. All animals in the PTX-FC group died within 4 days after the operation. All animals survived when supplied calcium in the diet. However, serum calcium levels were higher in the PTX-HC than the SHAM group. The PTX-NC group demonstrated the most representative modeling of primary hypothyroidism. Serum calcium levels decreased and phosphorus levels increased, and bone volume was increased. All animals survived without further treatment and did not show nephrotoxicity including calcium deposits. These findings demonstrate that PTX animal models produced by using the fluorescent-identification method, and fed a 0.5% calcium diet, are appropriate for hypoparathyroidism treatment studies.

  18. Standardization of A Physiologic Hypoparathyroidism Animal Model.

    Directory of Open Access Journals (Sweden)

    Soo Yeon Jung

    Full Text Available Ideal hypoparathyroidism animal models are a prerequisite to developing new treatment modalities for this disorder. The purpose of this study was to evaluate the feasibility of a model whereby rats were parathyroidectomized (PTX using a fluorescent-identification method and the ideal calcium content of the diet was determined. Thirty male rats were divided into surgical sham (SHAM, n = 5 and PTX plus 0, 0.5, and 2% calcium diet groups (PTX-FC (n = 5, PTX-NC (n = 10, and PTX-HC (n = 10, respectively. Serum parathyroid hormone levels decreased to non-detectable levels in all PTX groups. All animals in the PTX-FC group died within 4 days after the operation. All animals survived when supplied calcium in the diet. However, serum calcium levels were higher in the PTX-HC than the SHAM group. The PTX-NC group demonstrated the most representative modeling of primary hypothyroidism. Serum calcium levels decreased and phosphorus levels increased, and bone volume was increased. All animals survived without further treatment and did not show nephrotoxicity including calcium deposits. These findings demonstrate that PTX animal models produced by using the fluorescent-identification method, and fed a 0.5% calcium diet, are appropriate for hypoparathyroidism treatment studies.

  19. Development of animal models of otitis media.

    Science.gov (United States)

    Park, Moo Kyun; Lee, Byung Don

    2013-04-01

    Otitis media is defined as inflammation of the middle ear, including the auditory ossicles and the Eustachian tube. Otitis media is a major health problem in many societies. The causes of otitis media includes infection and anatomic/physiologic, host, and environmental factors. In general, otitis media is a childhood disease, and anatomic and physiologic changes have great effects on its development. Thus, in vitro or human experimental studies of otitis media are difficult. Several experimental animal models have been introduced to investigate the pathogenesis and treatment of otitis media. However, none are ideal. The aim of this review is to provide a brief overview of the current status of animal models of otitis media with effusion, acute otitis media, and cholesteatoma. This review will assist determination of the most appropriate animal models of otitis media.

  20. Animal models for Gaucher disease research

    Directory of Open Access Journals (Sweden)

    Tamar Farfel-Becker

    2011-11-01

    Full Text Available Gaucher disease (GD, the most common lysosomal storage disorder (LSD, is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.

  1. Animal models of asthma: utility and limitations

    Directory of Open Access Journals (Sweden)

    Aun MV

    2017-11-01

    Full Text Available Marcelo Vivolo Aun,1,2 Rafael Bonamichi-Santos,1,2 Fernanda Magalhães Arantes-Costa,2 Jorge Kalil,1 Pedro Giavina-Bianchi1 1Clinical Immunology and Allergy Division, Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil, 2Laboratory of Experimental Therapeutics (LIM20, Department of Internal Medicine, University of Sao Paulo, Sao Paulo, Brazil Abstract: Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila, rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes

  2. Animal models of transcranial direct current stimulation: Methods and mechanisms.

    Science.gov (United States)

    Jackson, Mark P; Rahman, Asif; Lafon, Belen; Kronberg, Gregory; Ling, Doris; Parra, Lucas C; Bikson, Marom

    2016-11-01

    complexity of normal and pathological brain function, and how recent studies have already indicated more sophisticated approaches are necessary. One tDCS theory regarding "functional targeting" suggests the specificity of tDCS effects are possible by modulating ongoing function (plasticity). Use of animal models of disease are summarized including pain, movement disorders, stroke, and epilepsy. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Molecular markers and mechanisms of stroke: RNA studies of blood in animals and humans

    Science.gov (United States)

    Sharp, Frank R; Jickling, Glen C; Stamova, Boryana; Tian, Yingfang; Zhan, Xinhua; Liu, DaZhi; Kuczynski, Beth; Cox, Christopher D; Ander, Bradley P

    2011-01-01

    Whole genome expression microarrays can be used to study gene expression in blood, which comes in part from leukocytes, immature platelets, and red blood cells. Since these cells are important in the pathogenesis of stroke, RNA provides an index of these cellular responses to stroke. Our studies in rats have shown specific gene expression changes 24 hours after ischemic stroke, hemorrhage, status epilepticus, hypoxia, hypoglycemia, global ischemia, and following brief focal ischemia that simulated transient ischemic attacks in humans. Human studies show gene expression changes following ischemic stroke. These gene profiles predict a second cohort with >90% sensitivity and specificity. Gene profiles for ischemic stroke caused by large-vessel atherosclerosis and cardioembolism have been described that predict a second cohort with >85% sensitivity and specificity. Atherosclerotic genes were associated with clotting, platelets, and monocytes, and cardioembolic genes were associated with inflammation, infection, and neutrophils. These gene profiles predicted the cause of stroke in 58% of cryptogenic patients. These studies will provide diagnostic, prognostic, and therapeutic markers, and will advance our understanding of stroke in humans. New techniques to measure all coding and noncoding RNAs along with alternatively spliced transcripts will markedly advance molecular studies of human stroke. PMID:21505474

  4. Efficacy of Alteplase® in a mouse model of acute ischemic stroke: a retrospective pooled analysis

    Science.gov (United States)

    Orset, Cyrille; Haelewyn, Benoit; Allan, Stuart M.; Ansar, Saema; Campos, Francesco; Cho, Tae Hee; Durand, Anne; El Amki, Mohamad; Fatar, Marc; Garcia-Yébenes, Isaac; Gauberti, Maxime; Grudzenski, Saskia; Lizasoain, Ignacio; Lo, Eng; Macrez, Richard; Margaill, Isabelle; Maysami, Samaneh; Meairs, Stephen; Nighoghossian, Norbert; Orbe, Josune; Paramo, Jose Antonio; Parienti, Jean-Jacques; Rothwell, Nancy J.; Rubio, Marina; Waeber, Christian; Young, Alan R.

    2016-01-01

    Background and purpose The debate over the fact that experimental drugs proposed for the treatment of stroke fail in the translation to the clinical situation, has attracted considerable attention in the literature. In this context, we present a retrospective pooled analysis of a large dataset from pre-clinical studies, in order to examine the effects of early versus late administration of intravenous recombinant tissue type plasminogen activator (rt-PA). Methods We collected data from 26 individual studies from 9 international centers (13 researchers, 716 animals) that compared rt-PA to controls, in a unique mouse model of thromboembolic stroke induced by an in situ injection of thrombin into the middle cerebral artery. Studies were classified into early (stroke in mice. The power analysis reveals that a multi-center trial would require 123 animals per group instead of 40 for a single center trial. PMID:27032444

  5. Are animal models predictive for humans?

    Directory of Open Access Journals (Sweden)

    Greek Ray

    2009-01-01

    Full Text Available Abstract It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is not surprising considering what we have learned from fields such evolutionary and developmental biology, gene regulation and expression, epigenetics, complexity theory, and comparative genomics.

  6. Henipavirus Infections: Lessons from Animal Models

    Directory of Open Access Journals (Sweden)

    Kévin P. Dhondt

    2013-04-01

    Full Text Available The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed.

  7. The wobbler mouse, an ALS animal model

    DEFF Research Database (Denmark)

    Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas

    2013-01-01

    This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...

  8. Animal models of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Pérez-Rial, Sandra; Girón-Martínez, Álvaro; Peces-Barba, Germán

    2015-03-01

    Animal models of disease have always been welcomed by the scientific community because they provide an approach to the investigation of certain aspects of the disease in question. Animal models of COPD cannot reproduce the heterogeneity of the disease and usually only manage to represent the disease in its milder stages. Moreover, airflow obstruction, the variable that determines patient diagnosis, not always taken into account in the models. For this reason, models have focused on the development of emphysema, easily detectable by lung morphometry, and have disregarded other components of the disease, such as airway injury or associated vascular changes. Continuous, long-term exposure to cigarette smoke is considered the main risk factor for this disease, justifying the fact that the cigarette smoke exposure model is the most widely used. Some variations on this basic model, related to exposure time, the association of other inducers or inhibitors, exacerbations or the use of transgenic animals to facilitate the identification of pathogenic pathways have been developed. Some variations or heterogeneity of this disease, then, can be reproduced and models can be designed for resolving researchers' questions on disease identification or treatment responses. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  9. Large Mammalian Animal Models of Heart Disease

    Directory of Open Access Journals (Sweden)

    Paula Camacho

    2016-10-01

    Full Text Available Due to the biological complexity of the cardiovascular system, the animal model is an urgent pre-clinical need to advance our knowledge of cardiovascular disease and to explore new drugs to repair the damaged heart. Ideally, a model system should be inexpensive, easily manipulated, reproducible, a biological representative of human disease, and ethically sound. Although a larger animal model is more expensive and difficult to manipulate, its genetic, structural, functional, and even disease similarities to humans make it an ideal model to first consider. This review presents the commonly-used large animals—dog, sheep, pig, and non-human primates—while the less-used other large animals—cows, horses—are excluded. The review attempts to introduce unique points for each species regarding its biological property, degrees of susceptibility to develop certain types of heart diseases, and methodology of induced conditions. For example, dogs barely develop myocardial infarction, while dilated cardiomyopathy is developed quite often. Based on the similarities of each species to the human, the model selection may first consider non-human primates—pig, sheep, then dog—but it also depends on other factors, for example, purposes, funding, ethics, and policy. We hope this review can serve as a basic outline of large animal models for cardiovascular researchers and clinicians.

  10. [Skin defect modeling in experimental animals].

    Science.gov (United States)

    Oleshko, A N; Kornienko, V V; Tkachenko, Yu A; Kurganskaya, V A

    2015-02-01

    To assess the skin regeneration and explore new medical devices for the treatment of skin defects is necessary to conduct long-term experiments using laboratory animals. Currently, there are many methods for skin trauma modeling but most of them have disadvantages that limit their use. The purpose of this work - the development of an experimental model of the formation of skin defect of various etiologies with the specified parameters of depth and area of damage to the absence of systemic effects on the animal's body. We have developed an installation that allows us to form a skin defect of mechanical, thermal and chemical etiology with area from 1.76 cm2 to 2.0 cm2. The experiment was conducted on 18 male laboratory rats to examine the effectiveness of current method and control the depth and area of the defect. As a result of the new methodology, we were able to carry out simulation skin injuries of different etiology on laboratory animals in the short term and reduce the severity of injuries to extend the life span of animals to monitor the repair processes, as well as to standardize the modeling of injuries according to the criteria of area and depth of the defect.

  11. Phenotyping animal models of diabetic neuropathy

    DEFF Research Database (Denmark)

    Biessels, G J; Bril, V; Calcutt, N A

    2014-01-01

    of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted......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....... The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current...

  12. Dynamics of myelin content decrease in the rat stroke model

    Science.gov (United States)

    Kisel, A.; Khodanovich, M.; Atochin, D.; Mustafina, L.; Yarnykh, V.

    2017-08-01

    The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures.

  13. Animal models of anxiety disorders and stress

    Directory of Open Access Journals (Sweden)

    Alline C. Campos

    2013-01-01

    Full Text Available Anxiety and stress-related disorders are severe psychiatric conditions that affect performance in daily tasks and represent a high cost to public health. The initial observation of Charles Darwin that animals and human beings share similar characteristics in the expression of emotion raise the possibility of studying the mechanisms of psychiatric disorders in other mammals (mainly rodents. The development of animal models of anxiety and stress has helped to identify the pharmacological mechanisms and potential clinical effects of several drugs. Animal models of anxiety are based on conflict situations that can generate opposite motivational states induced by approach-avoidance situations. The present review revisited the main rodent models of anxiety and stress responses used worldwide. Here we defined as “ethological” the tests that assess unlearned/unpunished responses (such as the elevated plus maze, light-dark box, and open field, whereas models that involve learned/punished responses are referred to as “conditioned operant conflict tests” (such as the Vogel conflict test. We also discussed models that involve mainly classical conditioning tests (fear conditioning. Finally, we addressed the main protocols used to induce stress responses in rodents, including psychosocial (social defeat and neonatal isolation stress, physical (restraint stress, and chronic unpredictable stress.

  14. Fantastic animals as an experimental model to teach animal adaptation

    Science.gov (United States)

    Guidetti, Roberto; Baraldi, Laura; Calzolai, Caterina; Pini, Lorenza; Veronesi, Paola; Pederzoli, Aurora

    2007-01-01

    Background Science curricula and teachers should emphasize evolution in a manner commensurate with its importance as a unifying concept in science. The concept of adaptation represents a first step to understand the results of natural selection. We settled an experimental project of alternative didactic to improve knowledge of organism adaptation. Students were involved and stimulated in learning processes by creative activities. To set adaptation in a historic frame, fossil records as evidence of past life and evolution were considered. Results The experimental project is schematized in nine phases: review of previous knowledge; lesson on fossils; lesson on fantastic animals; planning an imaginary world; creation of an imaginary animal; revision of the imaginary animals; adaptations of real animals; adaptations of fossil animals; and public exposition. A rubric to evaluate the student's performances is reported. The project involved professors and students of the University of Modena and Reggio Emilia and of the "G. Marconi" Secondary School of First Degree (Modena, Italy). Conclusion The educational objectives of the project are in line with the National Indications of the Italian Ministry of Public Instruction: knowledge of the characteristics of living beings, the meanings of the term "adaptation", the meaning of fossils, the definition of ecosystem, and the particularity of the different biomes. At the end of the project, students will be able to grasp particular adaptations of real organisms and to deduce information about the environment in which the organism evolved. This project allows students to review previous knowledge and to form their personalities. PMID:17767729

  15. Spatiotemporal epidemic models for rabies among animals

    Directory of Open Access Journals (Sweden)

    Shigui Ruan

    2017-08-01

    Full Text Available Rabies is a serious concern to public health and wildlife management worldwide. Over the last three decades, various mathematical models have been proposed to study the transmission dynamics of rabies. In this paper we provide a mini-review on some reaction-diffusion models describing the spatial spread of rabies among animals. More specifically, we introduce the susceptible-exposed-infectious models for the spatial transmission of rabies among foxes (Murray et al., 1986, the spatiotemporal epidemic model for rabies among raccoons (Neilan and Lenhart, 2011, the diffusive rabies model for skunk and bat interactions (Bonchering et al., 2012, and the reaction-diffusion model for rabies among dogs (Zhang et al., 2012. Numerical simulations on the spatiotemporal dynamics of these models from these papers are presented.

  16. Antidiabetic dietary materials and animal models.

    Science.gov (United States)

    Wang, Sunan; Zhu, Fan

    2016-07-01

    The ever-increasing occurrence of diabetes worldwide demands cost-effective anti-diabetic strategies. Food-based materials have great potential as efficient anti-diabetic agents. Focusing on the literatures of the recent 5years, this review summarizes the methods, findings, and limitations of each research involving non-medicinal foods (individual and mixed) and diabetic animal models. Various types of fruits, vegetables, legumes, cereals, spices, beverages, oilseeds, and edible oils showed antidiabetic effects in different animal models. Animal feeding trials rarely had identical designs in food doses, feeding schedules, and routes of administration, as well as biochemical markers for antidiabetic evaluation. Various possible cellular and metabolic targets were speculated for the anti-hyperglycemic effects of the dietary materials, and the molecular mechanisms of action remain to be better explored. Short-term (maximum 16weeks) antidiabetic studies have been established. Limited safety/tolerability data are available for antidiabetic dietary materials. Findings from current animal studies present a generic antidiabetic dietary pattern associated with plant-based whole foods, which agrees well with the findings of epidemiological studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial...

  18. Microparticles and cancer thrombosis in animal models.

    Science.gov (United States)

    Mege, Diane; Mezouar, Soraya; Dignat-George, Françoise; Panicot-Dubois, Laurence; Dubois, Christophe

    2016-04-01

    Cancer-associated venous thromboembolism (VTE) constitutes the second cause of death after cancer. Many risk factors for cancer-associated VTE have been identified, among them soluble tissue factor and microparticles (MPs). Few data are available about the implication of MPs in cancer associated-VTE through animal model of cancer. The objective of the present review was to report the state of the current literature about MPs and cancer-associated VTE in animal model of cancer. Fourteen series have reported the role of MPs in cancer-associated VTE, through three main mouse models: ectopic or orthotopic tumor induction, experimental metastasis by intravenous injection of tumor cells into the lateral tail vein of the mouse. Pancreatic cancer is the most used animal model, due to its high rate of cancer-associated VTE. All the series reported that tumor cell-derived MPs can promote thrombus formation in TF-dependent manner. Some authors reported also the implication of phosphatidylserine and PSGL1 in the generation of thrombin. Moreover, MPs seem to be implicated in cancer progression through a coagulation-dependent mechanism secondary to thrombocytosis, or a mechanism implicating the regulation of the immune response. For these reasons, few authors have reported that antiplatelet and anticoagulant treatments may prevent tumor progression and the formation of metastases in addition of coagulopathy. © 2016 Elsevier Ltd. All rights reserved.

  19. Experimental animal modelling for TB vaccine development

    Directory of Open Access Journals (Sweden)

    Pere-Joan Cardona

    2017-03-01

    Full Text Available Research for a novel vaccine to prevent tuberculosis is an urgent medical need. The current vaccine, BCG, has demonstrated a non-homogenous efficacy in humans, but still is the gold standard to be improved upon. In general, the main indicator for testing the potency of new candidates in animal models is the reduction of the bacillary load in the lungs at the acute phase of the infection. Usually, this reduction is similar to that induced by BCG, although in some cases a weak but significant improvement can be detected, but none of candidates are able to prevent establishment of infection. The main characteristics of several laboratory animals are reviewed, reflecting that none are able to simulate the whole characteristics of human tuberculosis. As, so far, no surrogate of protection has been found, it is important to test new candidates in several models in order to generate convincing evidence of efficacy that might be better than that of BCG in humans. It is also important to investigate the use of “in silico” and “ex vivo” models to better understand experimental data and also to try to replace, or at least reduce and refine experimental models in animals.

  20. Animal models of age related macular degeneration

    Science.gov (United States)

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  1. Deformation Models Tracking, Animation and Applications

    CERN Document Server

    Torres, Arnau; Gómez, Javier

    2013-01-01

    The computational modelling of deformations has been actively studied for the last thirty years. This is mainly due to its large range of applications that include computer animation, medical imaging, shape estimation, face deformation as well as other parts of the human body, and object tracking. In addition, these advances have been supported by the evolution of computer processing capabilities, enabling realism in a more sophisticated way. This book encompasses relevant works of expert researchers in the field of deformation models and their applications.  The book is divided into two main parts. The first part presents recent object deformation techniques from the point of view of computer graphics and computer animation. The second part of this book presents six works that study deformations from a computer vision point of view with a common characteristic: deformations are applied in real world applications. The primary audience for this work are researchers from different multidisciplinary fields, s...

  2. Animal models of maternal nutrition and altered offspring bone structure – Bone development across the lifecourse

    OpenAIRE

    SA Lanham; C Bertram; C Cooper; ROC Oreffo

    2011-01-01

    It is widely accepted that the likelihood of offspring developing heart disease, stroke, or diabetes in later life, is influenced by the their in utero environment and maternal nutrition. There is increasing epidemiological evidence that osteoporosis in the offspring may also be influenced by the mother’s nutrition during pregnancy. This review provides evidence from a range of animal models that supports the epidemiological data; suggesting that lifelong bone development and growth in offspr...

  3. The site of embolization related to infarct size, oedema and clinical outcome in a rat stroke model - further translational stroke research

    DEFF Research Database (Denmark)

    Overgaard, Karsten; Rasmussen, Rune S; Johansen, Flemming F

    2010-01-01

    Reliable models are essential for translational stroke research to study the pathophysiology of ischaemic stroke in an effort to find therapies that may ultimately reduce oedema, infarction and mortality in the clinic. The purpose of this study was to investigate the relation between the site...... of arterial embolization and the subsequent oedema, infarction and clinical outcome in a rat embolic stroke model....

  4. Thrombolytic and anticoagulation treatment in a rat embolic stroke model

    DEFF Research Database (Denmark)

    Rasmussen, Rune Skovgaard; Overgaard, K; Meden, P

    2003-01-01

    OBJECTIVES: The effects of pentasaccharide (PENTA), given alone or combined with thrombolysis using recombinant tissue plasminogen activator (rt-PA), on infarct size and clinical outcome were evaluated in a rat embolic stroke model. MATERIALS AND METHODS: Ninety-two rats were embolized unilaterally...... group, 4% (P treatment. Compared with rt-PA treatment alone, 0.5 mg/kg PENTA...... alone or combined with rt-PA did not significantly increase mortality or tendency for hemorrhage....

  5. Animal models of compulsive eating behavior.

    Science.gov (United States)

    Di Segni, Matteo; Patrono, Enrico; Patella, Loris; Puglisi-Allegra, Stefano; Ventura, Rossella

    2014-10-22

    Eating disorders are multifactorial conditions that can involve a combination of genetic, metabolic, environmental, and behavioral factors. Studies in humans and laboratory animals show that eating can also be regulated by factors unrelated to metabolic control. Several studies suggest a link between stress, access to highly palatable food, and eating disorders. Eating "comfort foods" in response to a negative emotional state, for example, suggests that some individuals overeat to self-medicate. Clinical data suggest that some individuals may develop addiction-like behaviors from consuming palatable foods. Based on this observation, "food addiction" has emerged as an area of intense scientific research. A growing body of evidence suggests that some aspects of food addiction, such as compulsive eating behavior, can be modeled in animals. Moreover, several areas of the brain, including various neurotransmitter systems, are involved in the reinforcement effects of both food and drugs, suggesting that natural and pharmacological stimuli activate similar neural systems. In addition, several recent studies have identified a putative connection between neural circuits activated in the seeking and intake of both palatable food and drugs. The development of well-characterized animal models will increase our understanding of the etiological factors of food addiction and will help identify the neural substrates involved in eating disorders such as compulsive overeating. Such models will facilitate the development and validation of targeted pharmacological therapies.

  6. Animal Models of Compulsive Eating Behavior

    Directory of Open Access Journals (Sweden)

    Matteo Di Segni

    2014-10-01

    Full Text Available Eating disorders are multifactorial conditions that can involve a combination of genetic, metabolic, environmental, and behavioral factors. Studies in humans and laboratory animals show that eating can also be regulated by factors unrelated to metabolic control. Several studies suggest a link between stress, access to highly palatable food, and eating disorders. Eating “comfort foods” in response to a negative emotional state, for example, suggests that some individuals overeat to self-medicate. Clinical data suggest that some individuals may develop addiction-like behaviors from consuming palatable foods. Based on this observation, “food addiction” has emerged as an area of intense scientific research. A growing body of evidence suggests that some aspects of food addiction, such as compulsive eating behavior, can be modeled in animals. Moreover, several areas of the brain, including various neurotransmitter systems, are involved in the reinforcement effects of both food and drugs, suggesting that natural and pharmacological stimuli activate similar neural systems. In addition, several recent studies have identified a putative connection between neural circuits activated in the seeking and intake of both palatable food and drugs. The development of well-characterized animal models will increase our understanding of the etiological factors of food addiction and will help identify the neural substrates involved in eating disorders such as compulsive overeating. Such models will facilitate the development and validation of targeted pharmacological therapies.

  7. Animal Models Utilized in HTLV-1 Research

    Directory of Open Access Journals (Sweden)

    Amanda R. Panfil

    2013-01-01

    Full Text Available Since the isolation and discovery of human T-cell leukemia virus type 1 (HTLV-1 over 30 years ago, researchers have utilized animal models to study HTLV-1 transmission, viral persistence, virus-elicited immune responses, and HTLV-1-associated disease development (ATL, HAM/TSP. Non-human primates, rabbits, rats, and mice have all been used to help understand HTLV-1 biology and disease progression. Non-human primates offer a model system that is phylogenetically similar to humans for examining viral persistence. Viral transmission, persistence, and immune responses have been widely studied using New Zealand White rabbits. The advent of molecular clones of HTLV-1 has offered the opportunity to assess the importance of various viral genes in rabbits, non-human primates, and mice. Additionally, over-expression of viral genes using transgenic mice has helped uncover the importance of Tax and Hbz in the induction of lymphoma and other lymphocyte-mediated diseases. HTLV-1 inoculation of certain strains of rats results in histopathological features and clinical symptoms similar to that of humans with HAM/TSP. Transplantation of certain types of ATL cell lines in immunocompromised mice results in lymphoma. Recently, “humanized” mice have been used to model ATL development for the first time. Not all HTLV-1 animal models develop disease and those that do vary in consistency depending on the type of monkey, strain of rat, or even type of ATL cell line used. However, the progress made using animal models cannot be understated as it has led to insights into the mechanisms regulating viral replication, viral persistence, disease development, and, most importantly, model systems to test disease treatments.

  8. Animal Models of Cancer-Associated Hypercalcemia.

    Science.gov (United States)

    Kohart, Nicole A; Elshafae, Said M; Breitbach, Justin T; Rosol, Thomas J

    2017-04-13

    Cancer-associated hypercalcemia (CAH) is a frequently-occurring paraneoplastic syndrome that contributes to substantial patient morbidity and occurs in both humans and animals. Patients with CAH are often characterized by markedly elevated serum calcium concentrations that result in a range of clinical symptoms involving the nervous, gastrointestinal and urinary systems. CAH is caused by two principle mechanisms; humorally-mediated and/or through local osteolytic bone metastasis resulting in excessive calcium release from resorbed bone. Humoral hypercalcemia of malignancy (HHM) is the most common mechanism and is due to the production and release of tumor-associated cytokines and humoral factors, such as parathyroid hormone-related protein (PTHrP), that act at distant sites to increase serum calcium concentrations. Local osteolytic hypercalcemia (LOH) occurs when primary or metastatic bone tumors act locally by releasing factors that stimulate osteoclast activity and bone resorption. LOH is a less frequent cause of CAH and in some cases can induce hypercalcemia in concert with HHM. Rarely, ectopic production of parathyroid hormone has been described. PTHrP-mediated hypercalcemia is the most common mechanism of CAH in human and canine malignancies and is recognized in other domestic species. Spontaneous and experimentally-induced animal models have been developed to study the mechanisms of CAH. These models have been essential for the evaluation of novel approaches and adjuvant therapies to manage CAH. This review will highlight the comparative aspects of CAH in humans and animals with a discussion of the available animal models used to study the pathogenesis of this important clinical syndrome.

  9. Potential animal models of seasonal affective disorder.

    Science.gov (United States)

    Workman, Joanna L; Nelson, Randy J

    2011-01-01

    Seasonal affective disorder (SAD) is characterized by depressive episodes during winter that are alleviated during summer and by morning bright light treatment. Currently, there is no animal model of SAD. However, it may be possible to use rodents that respond to day length (photoperiod) to understand how photoperiod can shape the brain and behavior in humans. As nights lengthen in the autumn, the duration of the nightly elevation of melatonin increase; seasonally breeding animals use this information to orchestrate seasonal changes in physiology and behavior. SAD may originate from the extended duration of nightly melatonin secretion during fall and winter. These similarities between humans and rodents in melatonin secretion allows for comparisons with rodents that express more depressive-like responses when exposed to short day lengths. For instance, Siberian hamsters, fat sand rats, Nile grass rats, and Wistar rats display a depressive-like phenotype when exposed to short days. Current research in depression and animal models of depression suggests that hippocampal plasticity may underlie the symptoms of depression and depressive-like behaviors, respectively. It is also possible that day length induces structural changes in human brains. Many seasonally breeding rodents undergo changes in whole brain and hippocampal volume in short days. Based on strict validity criteria, there is no animal model of SAD, but rodents that respond to reduced day lengths may be useful to approximate the neurobiological phenomena that occur in people with SAD, leading to greater understanding of the etiology of the disorder as well as novel therapeutic interventions. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. An animal model to study regenerative endodontics.

    Science.gov (United States)

    Torabinejad, Mahmoud; Corr, Robert; Buhrley, Matthew; Wright, Kenneth; Shabahang, Shahrokh

    2011-02-01

    A growing body of evidence is demonstrating the possibility for regeneration of tissues within the pulp space and continued root development in teeth with necrotic pulps and open apices. There are areas of research related to regenerative endodontics that need to be investigated in an animal model. The purpose of this study was to investigate ferret cuspid teeth as a model to investigate factors involved in regenerative endodontics. Six young male ferrets between the ages of 36-133 days were used in this investigation. Each animal was anesthetized and perfused with 10% buffered formalin. Block sections including the mandibular and maxillary cuspid teeth and their surrounding periapical tissues were obtained, radiographed, decalcified, sectioned, and stained with hematoxylin-eosin to determine various stages of apical closure in these teeth. The permanent mandibular and maxillary cuspid teeth with open apices erupted approximately 50 days after birth. Initial signs of closure of the apical foramen in these teeth were observed between 90-110 days. Complete apical closure was observed in the cuspid teeth when the animals were 133 days old. Based on the experiment, ferret cuspid teeth can be used to investigate various factors involved in regenerative endodontics that cannot be tested in human subjects. The most appropriate time to conduct the experiments would be when the ferrets are between the ages of 50 and 90 days. Copyright © 2011. Published by Elsevier Inc.

  11. Beneficial effects of isovolemic hemodilution using a perfluorocarbon emulsion in a stroke model.

    Science.gov (United States)

    Kline, R A; Negendank, W; McCoy, L; Berguer, R

    1991-08-01

    In a clinically applicable cat stroke model, 16 purpose-bred adult animals were used to evaluate the beneficial effects of two treatment regimens: isovolemic hemodilution with either a perfluorocarbon emulsion or dextran 40 (a glucose polymer). Animals that received these treatment regimens were then compared with a control group of untreated animals. Focal cerebral infarctions were produced by transorbital ligation of the left middle cerebral artery. The randomly allocated treatment arms of the study were instituted 3 hours after ligation of the middle cerebral artery, thereby simulating a human clinical situation. In vivo mitochondrial metabolic activity of the peri-infarct cerebral tissue was continually assessed by means of a multiwavelength near-infrared spectrophotometer. This allowed measurement of cellular oxygenation at the cytochrome aa3 level, the terminal member of the cytochrome chain. Sequential proton-based magnetic resonance imaging was used to measure intracerebral water in vivo. Cardiac output, oxygen consumption/delivery, chemical, histologic, and rheologic parameters were also assessed. The data collected were analyzed by group means and standard statistical analyses, which revealed that the group treated with the perfluorocarbon emulsion had both less brain edema in the early post-infarct period (p less than 0.05), as well as a higher level of oxidation of cytochrome aa3 (p less than or equal to 0.025). This evidence supports the premise that isovolemic hemodilution with an oxygen-carrying hemodiluent may be beneficial in the treatment of ischemic strokes.

  12. Animal models for HIV/AIDS research

    Science.gov (United States)

    Hatziioannou, Theodora; Evans, David T.

    2015-01-01

    The AIDS pandemic continues to present us with unique scientific and public health challenges. Although the development of effective antiretroviral therapy has been a major triumph, the emergence of drug resistance requires active management of treatment regimens and the continued development of new antiretroviral drugs. Moreover, despite nearly 30 years of intensive investigation, we still lack the basic scientific knowledge necessary to produce a safe and effective vaccine against HIV-1. Animal models offer obvious advantages in the study of HIV/AIDS, allowing for a more invasive investigation of the disease and for preclinical testing of drugs and vaccines. Advances in humanized mouse models, non-human primate immunogenetics and recombinant challenge viruses have greatly increased the number and sophistication of available mouse and simian models. Understanding the advantages and limitations of each of these models is essential for the design of animal studies to guide the development of vaccines and antiretroviral therapies for the prevention and treatment of HIV-1 infection. PMID:23154262

  13. Experimental Oral Candidiasis in Animal Models

    Science.gov (United States)

    Samaranayake, Yuthika H.; Samaranayake, Lakshman P.

    2001-01-01

    Oral candidiasis is as much the final outcome of the vulnerability of the host as of the virulence of the invading organism. We review here the extensive literature on animal experiments mainly appertaining to the host predisposing factors that initiate and perpetuate these infections. The monkey, rat, and mouse are the choice models for investigating oral candidiasis, but comparisons between the same or different models appear difficult, because of variables such as the study design, the number of animals used, their diet, the differences in Candida strains, and the duration of the studies. These variables notwithstanding, the following could be concluded. (i) The primate model is ideal for investigating Candida-associated denture stomatitis since both erythematous and pseudomembranous lesions have been produced in monkeys with prosthetic plates; they are, however, expensive and difficult to obtain and maintain. (ii) The rat model (both Sprague-Dawley and Wistar) is well proven for observing chronic oral candidal colonization and infection, due to the ease of breeding and handling and their ready availability. (iii) Mice are similar, but in addition there are well characterized variants simulating immunologic and genetic abnormalities (e.g., athymic, euthymic, murine-acquired immune deficiency syndrome, and severe combined immunodeficient models) and hence are used for short-term studies relating the host immune response and oral candidiasis. Nonetheless, an ideal, relatively inexpensive model representative of the human oral environment in ecological and microbiological terms is yet to be described. Until such a model is developed, researchers should pay attention to standardization of the experimental protocols described here to obtain broadly comparable and meaningful data. PMID:11292645

  14. Image-guided pro-angiogenic therapy in diabetic stroke mouse models using a multi-modal nanoprobe.

    Science.gov (United States)

    Bai, Ying-Ying; Gao, Xihui; Wang, Yuan-Cheng; Peng, Xin-Gui; Chang, Di; Zheng, Shuyan; Li, Cong; Ju, Shenghong

    2014-01-01

    The efficacy of pro-angiogenic therapy is difficult to evaluate with current diagnostic modalities. The objectives were to develop a non-invasive imaging strategy to define the temporal characteristics of angiogenesis and to evaluate the response to pro-angiogenic therapy in diabetic stroke mouse models. A home-made ανβ3 integrin-targeted multi-modal nanoprobe was intravenously injected into mouse models at set time points after photothrombotic stroke. Magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging were carried out at 24 h post-injection. Bone marrow-derived endothelial progenitor cells (EPCs) were infused into the mouse models of ischemic stroke to stimulate angiogenesis. The peak signal intensity in the ischemic-angiogenic area of diabetic and wild-type mouse models was achieved on day 10, with significantly lower signal enhancement observed in the diabetic models. Although the signal intensity was significantly higher after EPC treatment in both models, the enhancement was less pronounced in the diabetic animals compared with the wild-type controls. Histological analysis revealed that the microvessel density and expression of β3 integrin were correlated with the signal intensity assessed with MRI and NIRF imaging. The non-invasive imaging method could be used for early and accurate evaluation of the response to pro-angiogenic therapy in diabetic stroke models.

  15. Scalp acupuncture attenuates neurological deficits in a rat model of hemorrhagic stroke.

    Science.gov (United States)

    Liu, Hao; Sun, Xiaowei; Zou, Wei; Leng, Mengtong; Zhang, Beng; Kang, Xiaoyu; He, Tao; Wang, Hui

    2017-06-01

    Hemorrhagic stroke accounts for approximately 15% of all stroke cases, and is associated with high morbidity and mortality. Limited human studies suggested that scalp acupuncture could facilitate functional recovery after cerebral hemorrhage. In the current study, we used an animal model of cerebral hemorrhage to examine the potential effects of scalp acupuncture. Adult male Sprague-Dawley rats received autologous blood (50μL) into the right caudate nucleus on the right side under pentobarbital anesthesia, and then received scalp acupuncture (DU20 through GB7 on the lesion side) or sham acupuncture (1cm to the right side of the acupoints) (n=10 per group). A group of rats receiving autologous blood into the caudate nucleus but no other intervention, as well as a group of rats receiving anesthesia but no blood injection to the brain (n=10 per group) were included as additional controls. Composite neuroscore, corner turn test, forelimb placing test, wire hang task and beam walking were used to evaluate the behavior of rats. Hematoxylin and Eosin (HE) staining was used to observe the histopathological changes. Western blot was used to detect the content of tumor necrosis factor alpha (TNF-α) and nuclear factor-KappaB (NFκB) protein expression. Scalp acupuncture attenuated neurological deficits (ptreatment. The brain content of TNF-α and NFκB was decreased (phemorrhagic stroke. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

    Directory of Open Access Journals (Sweden)

    Muhammad Nazrul Somchit

    2014-12-01

    Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

  17. Small-Animal Models of Zika Virus.

    Science.gov (United States)

    Julander, Justin G; Siddharthan, Venkatraman

    2017-12-16

    Zika virus (ZIKV) infection can result in serious consequences, including severe congenital manifestations, persistent infection in the testes, and neurologic sequelae. After a pandemic emergence, the virus has spread to much of North and South America and has been introduced to many countries outside of ZIKV-endemic areas as infected travelers return to their home countries. Rodent models have been important in gaining a better understanding of the wide range of disease etiologies associated with ZIKV infection and for the initial phase of developing countermeasures to prevent or treat viral infections. We discuss herein the advantages and disadvantages of small-animal models that have been developed to replicate various aspects of disease associated with ZIKV infection. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  18. Biokinetic models for radionuclides in experimental animals

    International Nuclear Information System (INIS)

    Morcillo, M. A.

    2003-01-01

    The biokinetic models for many radionuclides are, to a large extent, based on data obtained in experimental animals. The methods used in the experimental development of a biokinetic model can be classified in two groups (i) those applied during the experimental work, which include the activity determination of a given radionuclide at different times and in different biological media such as blood, serum, organs/tissues, urine, bile and faeces and (ii) those methods used for the analysis and study of the experimental data, based in mathematical tools. Some of these methods are reviewed,with special emphasis in the whole body macro autoradiography. To conclude, the contribution that this type of studies can have in two fields of radiation protection is discussed, namely optimization of dosimetric evaluations and decorporation of radionuclides. (Author)

  19. Advances in transgenic animal models and techniques.

    Science.gov (United States)

    Ménoret, Séverine; Tesson, Laurent; Remy, Séverine; Usal, Claire; Ouisse, Laure-Hélène; Brusselle, Lucas; Chenouard, Vanessa; Anegon, Ignacio

    2017-10-01

    On May 11th and 12th 2017 was held in Nantes, France, the international meeting "Advances in transgenic animal models and techniques" ( http://www.trm.univ-nantes.fr/ ). This biennial meeting is the fifth one of its kind to be organized by the Transgenic Rats ImmunoPhenomic (TRIP) Nantes facility ( http://www.tgr.nantes.inserm.fr/ ). The meeting was supported by private companies (SONIDEL, Scionics computer innovation, New England Biolabs, MERCK, genOway, Journal Disease Models and Mechanisms) and by public institutions (International Society for Transgenic Technology, University of Nantes, INSERM UMR 1064, SFR François Bonamy, CNRS, Région Pays de la Loire, Biogenouest, TEFOR infrastructure, ITUN, IHU-CESTI and DHU-Oncogeffe and Labex IGO). Around 100 participants, from France but also from different European countries, Japan and USA, attended the meeting.

  20. Animal Models of Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Eva Harris

    2012-01-01

    Full Text Available The development of animal models of dengue virus (DENV infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines.

  1. Stroke after coronary artery bypass grafting. Is there place for a stroke-risk stratification model?

    NARCIS (Netherlands)

    Noyez, L.; Swieten, H.A. van

    2009-01-01

    AIM: Preoperative carotid screening is common in the prevention of perioperative stroke. The authors describe our experience with selective screening of patients with a recent (<1 year) neurological event. Because many variables are related with the development of perioperative stroke we

  2. Models to Tailor Brain Stimulation Therapies in Stroke

    Directory of Open Access Journals (Sweden)

    E. B. Plow

    2016-01-01

    Full Text Available A great challenge facing stroke rehabilitation is the lack of information on how to derive targeted therapies. As such, techniques once considered promising, such as brain stimulation, have demonstrated mixed efficacy across heterogeneous samples in clinical studies. Here, we explain reasons, citing its one-type-suits-all approach as the primary cause of variable efficacy. We present evidence supporting the role of alternate substrates, which can be targeted instead in patients with greater damage and deficit. Building on this groundwork, this review will also discuss different frameworks on how to tailor brain stimulation therapies. To the best of our knowledge, our report is the first instance that enumerates and compares across theoretical models from upper limb recovery and conditions like aphasia and depression. Here, we explain how different models capture heterogeneity across patients and how they can be used to predict which patients would best respond to what treatments to develop targeted, individualized brain stimulation therapies. Our intent is to weigh pros and cons of testing each type of model so brain stimulation is successfully tailored to maximize upper limb recovery in stroke.

  3. [Analysis of dalbavancin in animal models].

    Science.gov (United States)

    Murillo, Óscar; El-Haj, Cristina

    2017-01-01

    Multiresistant Gram-positive infections continue to pose a major clinical challenge and the development of new antibiotics is always desirable. Dalbavancin is a lipoglycopeptide with a prolonged half-life that allows long dosing intervals. In experimental models, its activity has been evaluated in distinct models and microorganisms, which limits the conclusions that can be drawn; however, the largest number of studies have been conducted in Staphylococcus aureus infection. Overall, dalbavancin has shown concentration-dependent efficacy and the parameters best explaining its activity are maximal pharmacodynamic concentration/minimal inhibitory concentration and the area under the curve/minimal inhibitory concentration. In these experimental models, dalbavancin has shown good distribution, a prolonged half-life in all animal species and efficacy that is mostly similar to that of previous glycopeptides but with lower doses and with longer dosing intervals. Of note, the efficacy of dalbavancin is not altered by methicillin resistance or the glycopeptide sensitivity of S. aureus. In the case of difficult-to-treat staphylococcal infections (eg, endocarditis, foreign body infections), an adequate dosing interval and high dosage seem to play an important role in the efficacy of the drug. All in all, experimental models can still provide greater knowledge of this new antibiotic to guide clinical research and determine its role in the treatment of distinct infections produced by Gram-positive microorganisms. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  4. Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Nikravesh

    2011-11-01

    Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

  5. Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke.

    Science.gov (United States)

    Khodaparast, Navid; Hays, Seth A; Sloan, Andrew M; Fayyaz, Tabbassum; Hulsey, Daniel R; Rennaker, Robert L; Kilgard, Michael P

    2014-09-01

    Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into 3 groups: vagus nerve stimulation during rehabilitation (rehab), vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), prelesion training, postlesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed 1 week of recovery before postlesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All 17 trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to prelesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to prelesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared with rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation. © The Author(s) 2014.

  6. Animal models of chronic wound care

    DEFF Research Database (Denmark)

    Trøstrup, Hannah; Thomsen, Kim; Calum, Henrik

    2016-01-01

    Chronic wounds are a substantial clinical problem affecting millions of people worldwide. Pathophysiologically, chronic wounds are stuck in the inflammatory state of healing. The role of bacterial biofilms in suppression and perturbation of host response could be an explanation for this observation....... An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure) has to be taken...... into consideration as underlying pathophysiological mechanisms and comorbidities display tremendous variation in humans. Confounders such as infection, smoking, chronological age, sex, medication, metabolic disturbances, and renal impairment add to the difficulty in gaining systematic and comparable studies...

  7. Animal models for HCV and HBV studies

    Directory of Open Access Journals (Sweden)

    Isabelle Chemin

    2007-02-01

    Full Text Available

    The narrow host range of infection and lack of suitable tissue culture systems for the propagation of hepatitis B and C viruses are limitations that have prevented a more thorough understanding of persistent infection and the pathogenesis of chronic liver disease.

    Despite decades of intensive research and significant progresses in understanding of viral hepatitis, many basic questions and clinical problems still await to be resolved. For example, the HBV cellular receptor and related mechanisms of viral entry have not yet been identified. Little is also known about the function of certain non-structural viral products, such as the hepatitis B e antigen and the X protein, or about the role of excess hepadnavirus subviral particles circulating in the blood stream during infection. Furthermore, the molecular mechanisms involved in the development of hepatocellular carcinoma and the role of the immune system in determining the fate of infection are not fully understood.

    The reason for these drawbacks is essentially due to the lack of reliable cell-based in vitro infection systems and, most importantly, convenient animal models.

    This lack of knowledge has been partially overcome for hepatitis B virus (HBV, by the discovery and characterization of HBV-like viruses in wild animals while for hepatitis C virus (HCV, related flaviviruses have been used as surrogate systems.

    Other laboratories have developed transgenic mice that express virus gene products and/or support virus replication. Some HBV transgenic mouse models

  8. Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives

    Directory of Open Access Journals (Sweden)

    Mohan Kumar Pasupuleti

    2016-01-01

    Full Text Available Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.

  9. Animal Model of Acute Deep Vein Thrombosis

    International Nuclear Information System (INIS)

    Roy, Sumit; Laerum, Frode; Brosstad, Frank; Kvernebo, Knut; Sakariassen, Kjell S.

    1998-01-01

    Purpose: To develop an animal model of acute deep vein thrombosis (DVT). Methods: In part I of the study nine juvenile domestic pigs were used. Each external iliac vein was transluminally occluded with a balloon catheter. Thrombin was infused through a microcatheter in one leg according to one of the following protocols: (1) intraarterial (IA): 1250 U at 25 U/min in the common femoral artery (n= 3); (2) intravenous (IV): 5000 U in the popliteal vein at 500 U/min (n= 3), or at 100 U/min (n= 3). Saline was administered in the opposite leg. After the animals were killed, the mass of thrombus in the iliofemoral veins was measured. The pudendoepiploic (PEV), profunda femoris (PF), and popliteal veins (PV) were examined. Thrombosis in the tributaries of the superficial femoral vein (SFVt) was graded according to a three-point scale (0, +, ++). In part II of the study IV administration was further investigated in nine pigs using the following three regimens with 1000 U at 25 U/min serving as the control: (1) 1000 U at 100 U/min, (2) 250 U at 25 U/min, (3) 250 U at 6.25 U/min. Results: All animals survived. In part I median thrombus mass in the test limbs was 1.40 g as compared with 0.25 g in the controls (p= 0.01). PEV, PFV and PV were thrombosed in all limbs infused with thrombin. IV infusion was more effective in inducing thrombosis in both the parent veins (mass 1.32-1.78 g) and SVFt (++ in 4 of 6 legs), as compared with IA infusion (mass 0.0-1.16 g; SFVt ++ in 1 of 3 legs). In part II thrombus mass in axial veins ranged from 1.23 to 2.86 g, and showed no relationship with the dose of thrombin or the rate of infusion. Tributary thrombosis was less extensive with 250 U at 25 U/min than with the other regimens. Conclusion: Slow distal intravenous thrombin infusion in the hind legs of pigs combined with proximal venous occlusion induces thrombosis in the leg veins that closely resembles clinical DVT in distribution

  10. On the SU(2 vertical stroke 1) WZNW model and its statistical mechanics applications

    Energy Technology Data Exchange (ETDEWEB)

    Saleur, H. [CEA Centre d' Etudes de Saclay, 91 - Gif-sur-Yvette (France). Service de Physique Theorique]|[University of Southern California, Los Angeles, CA (United States). Dept. of Physics; Schomerus, V. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2006-11-15

    Motivated by a careful analysis of the Laplacian on the supergroup SU(2 vertical stroke 1) we formulate a proposal for the state space of the SU(2 vertical stroke 1) WZNW model. We then use properties of sl(2 vertical stroke 1) characters to compute the partition function of the theory. In the special case of level k=1 the latter is found to agree with the properly regularized partition function for the continuum limit of the integrable sl(2 vertical stroke 1)3- anti 3 super-spin chain. Some general conclusions applicable to other WZNW models (in particular the case k=-1/2) are also drawn. (orig.)

  11. RASopathies: unraveling mechanisms with animal models

    Directory of Open Access Journals (Sweden)

    Granton A. Jindal

    2015-08-01

    Full Text Available RASopathies are developmental disorders caused by germline mutations in the Ras-MAPK pathway, and are characterized by a broad spectrum of functional and morphological abnormalities. The high incidence of these disorders (∼1/1000 births motivates the development of systematic approaches for their efficient diagnosis and potential treatment. Recent advances in genome sequencing have greatly facilitated the genotyping and discovery of mutations in affected individuals, but establishing the causal relationships between molecules and disease phenotypes is non-trivial and presents both technical and conceptual challenges. Here, we discuss how these challenges could be addressed using genetically modified model organisms that have been instrumental in delineating the Ras-MAPK pathway and its roles during development. Focusing on studies in mice, zebrafish and Drosophila, we provide an up-to-date review of animal models of RASopathies at the molecular and functional level. We also discuss how increasingly sophisticated techniques of genetic engineering can be used to rigorously connect changes in specific components of the Ras-MAPK pathway with observed functional and morphological phenotypes. Establishing these connections is essential for advancing our understanding of RASopathies and for devising rational strategies for their management and treatment.

  12. Four-Stroke, Internal Combustion Engine Performance Modeling

    Science.gov (United States)

    Wagner, Richard C.

    In this thesis, two models of four-stroke, internal combustion engines are created and compared. The first model predicts the intake and exhaust processes using isentropic flow equations augmented by discharge coefficients. The second model predicts the intake and exhaust processes using a compressible, time-accurate, Quasi-One-Dimensional (Q1D) approach. Both models employ the same heat release and reduced-order modeling of the cylinder charge. Both include friction and cylinder loss models so that the predicted performance values can be compared to measurements. The results indicate that the isentropic-based model neglects important fluid mechanics and returns inaccurate results. The Q1D flow model, combined with the reduced-order model of the cylinder charge, is able to capture the dominant intake and exhaust fluid mechanics and produces results that compare well with measurement. Fluid friction, convective heat transfer, piston ring and skirt friction and temperature-varying specific heats in the working fluids are all shown to be significant factors in engine performance predictions. Charge blowby is shown to play a lesser role.

  13. Preclinical stroke research--advantages and disadvantages of the most common rodent models of focal ischaemia.

    Science.gov (United States)

    Macrae, I M

    2011-10-01

    This review describes the most commonly used rodent models and outcome measures in preclinical stroke research and discusses their strengths and limitations. Most models involve permanent or transient middle cerebral artery occlusion with therapeutic agents tested for their ability to reduce stroke-induced infarcts and improve neurological deficits. Many drugs have demonstrated preclinical efficacy but, other than thrombolytics, which restore blood flow, none have demonstrated efficacy in clinical trials. This failure to translate efficacy from bench to bedside is discussed alongside achievable steps to improve the ability of preclinical research to predict clinical efficacy: (i) Improvements in study quality and reporting. Study design must include randomization, blinding and predefined inclusion/exclusion criteria, and journal editors have the power to ensure statements on these and mortality data are included in preclinical publications. (ii) Negative and neutral studies must be published to enable preclinical meta-analyses and systematic reviews to more accurately predict drug efficacy in man. (iii) Preclinical groups should work within networks and agree on standardized procedures for assessing final infarct and functional outcome. This will improve research quality, timeliness and translational capacity. (iv) Greater uptake and improvements in non-invasive diagnostic imaging to detect and study potentially salvageable penumbral tissue, the target for acute neuroprotection. Drug effects on penumbra lifespan studied serially, followed by assessment of behavioural outcome and infarct within in the same animal group, will increase the power to detect drug efficacy preclinically. Similar progress in detecting drug efficacy clinically will follow from patient recruitment into acute stroke trials based on evidence of remaining penumbra. © 2011 The Author. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  14. Wound healing in animal models: review article

    Directory of Open Access Journals (Sweden)

    Fariba Jaffary

    2017-10-01

    Full Text Available Wound healing and reduction of its recovery time is one of the most important issues in medicine. Wound is defined as disruption of anatomy and function of normal skin. This injury could be the result of physical elements such as  surgical incision, hit or pressure cut of the skin and gunshot wound. Chemical or caustic burn is another category of wound causes that can be induced by acid or base contact irritation. Healing is a process of cellular and extracellular matrix interactions that occur in the damaged tissue. Wound healing consists of several stages including hemostasis, inflammatory phase, proliferative phase and new tissue formation which reconstructs by new collagen formation. Wounds are divided into acute and chronic types based on their healing time. Acute wounds have sudden onset and in normal individuals usually have healing process of less than 4 weeks without any residual side effects. In contrast, chronic wounds have gradual onset. Their inflammatory phase is prolonged and the healing process is stopped due to some background factors like diabetes, ischemia or local pressure. If the healing process lasts more than 4 weeks it will be classified as chronic wound. Despite major advances in the treatment of wounds, still finding effective modalities for healing wounds in the shortest possible time with the fewest side effects is a current challenge. In this review different phases of wound healing and clinical types of wound such as venous leg ulcer, diabetic foot ulcer and pressure ulcer are discussed. Also acute wound models (i.e burn wounds or incisional wound and chronic wound models (such as venous leg ulcers, diabetic foot ulcer, pressure ulcers or bedsore in laboratory animals are presented. This summary can be considered as a preliminary step to facilitate designing of more targeted and applied research in this area.

  15. Searching for better animal models of BPD: a perspective.

    Science.gov (United States)

    Ambalavanan, Namasivayam; Morty, Rory E

    2016-11-01

    There have been many efforts to develop good animal models of bronchopulmonary dysplasia (BPD) to better understand the pathophysiology and mechanisms underlying development of BPD as well as to test potential strategies for its prevention and treatment. This Perspectives summarizes the features of common animal models of BPD and the strengths and limitations of such models. Potential optimal approaches to development of animal models are indicated, with the underlying concepts that require emphasis. Copyright © 2016 the American Physiological Society.

  16. Modeling individual animal histories with multistate capture–recapture models

    Science.gov (United States)

    Lebreton, Jean-Dominique; Nichols, James D.; Barker, Richard J.; Pradel, Roger; Spendelow, Jeffrey A.

    2009-01-01

    Many fields of science begin with a phase of exploration and description, followed by investigations of the processes that account for observed patterns. The science of ecology is no exception, and recent decades have seen a focus on understanding key processes underlying the dynamics of ecological systems. In population ecology, emphasis has shifted from the state variable of population size to the demographic processes responsible for changes in this state variable: birth, death, immigration, and emigration. In evolutionary ecology, some of these same demographic processes, rates of birth and death, are also the determinants of fitness. In animal population ecology, the estimation of state variables and their associated vital rates is especially problematic because of the difficulties in sampling such populations and detecting individual animals. Indeed, early capture–recapture models were developed for the purpose of estimating population size, given the reality that all animals are not caught or detected at any sampling occasion. More recently, capture–recapture models for open populations were developed to draw inferences about survival in the face of these same sampling problems. The focus of this paper is on multi‐state mark–recapture models (MSMR), which first appeared in the 1970s but have undergone substantial development in the last 15 years. These models were developed to deal explicitly with biological variation, in that animals in different “states” (classes defined by location, physiology, behavior, reproductive status, etc.) may have different probabilities of survival and detection. Animal transitions between states are also stochastic and themselves of interest. These general models have proven to be extremely useful and provide a way of thinking about a remarkably wide range of important ecological processes. These methods are now at a stage of refinement and sophistication where they can readily be used by biologists to tackle a wide

  17. Digital creature creation: applied 3D modelling and animation for Australian animal visualization

    OpenAIRE

    Ung, Chandara

    2017-01-01

    This exegesis focuses on the investigative and studio research informing the digital construction of a diverse selection of Australian animals. A series of case studies of digital creature construction - the Jackie Dragon, Jabiru, Bandicoot, Eel, Blue Ringed Octopus and Fiddler Crab - will be outlined along with the key creation study of the Groper. Through investigating how visual research can inform the creation of 3D modelled and animated animal subjects and tracing their development proce...

  18. Logical Analysis of Data (LAD model for the early diagnosis of acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Hoehn Gerard

    2008-07-01

    Full Text Available Abstract Background Strokes are a leading cause of morbidity and the first cause of adult disability in the United States. Currently, no biomarkers are being used clinically to diagnose acute ischemic stroke. A diagnostic test using a blood sample from a patient would potentially be beneficial in treating the disease. Results A classification approach is described for differentiating between proteomic samples of stroke patients and controls, and a second novel predictive model is developed for predicting the severity of stroke as measured by the National Institutes of Health Stroke Scale (NIHSS. The models were constructed by applying the Logical Analysis of Data (LAD methodology to the mass peak profiles of 48 stroke patients and 32 controls. The classification model was shown to have an accuracy of 75% when tested on an independent validation set of 35 stroke patients and 25 controls, while the predictive model exhibited superior performance when compared to alternative algorithms. In spite of their high accuracy, both models are extremely simple and were developed using a common set consisting of only 3 peaks. Conclusion We have successfully identified 3 biomarkers that can detect ischemic stroke with an accuracy of 75%. The performance of the classification model on the validation set and on cross-validation does not deteriorate significantly when compared to that on the training set, indicating the robustness of the model. As in the case of the LAD classification model, the results of the predictive model validate the function constructed on our support-set for approximating the severity scores of stroke patients. The correlation and root mean absolute error of the LAD predictive model are consistently superior to those of the other algorithms used (Support vector machines, C4.5 decision trees, Logistic regression and Multilayer perceptron.

  19. The complete guide to blender graphics computer modeling and animation

    CERN Document Server

    Blain, John M

    2014-01-01

    Smoothly Leads Users into the Subject of Computer Graphics through the Blender GUIBlender, the free and open source 3D computer modeling and animation program, allows users to create and animate models and figures in scenes, compile feature movies, and interact with the models and create video games. Reflecting the latest version of Blender, The Complete Guide to Blender Graphics: Computer Modeling & Animation, 2nd Edition helps beginners learn the basics of computer animation using this versatile graphics program. This edition incorporates many new features of Blender, including developments

  20. Model of hospital-supported discharge after stroke

    DEFF Research Database (Denmark)

    Torp, Claus Rydahl; Vinkler, Sonja; Pedersen, Kirsten Damgaard

    2006-01-01

    BACKGROUND AND PURPOSE: Readmission rate within 6 months after a stroke is 40% to 50%. The purpose of the project was to evaluate whether an interdisciplinary stroke team could reduce length of hospital stay, readmission rate, increase patient satisfaction and reduce dependency of help. METHODS......: One hundred and ninety-eight patients with acute stroke were randomized into 103 patients whose discharge was supported by an interdisciplinary stroke team and 95 control patients who received standard aftercare. Baseline characteristics were comparable in the 2 groups. The patients were evaluated...... services. Furthermore, there was no significant difference in functional scores or patient satisfaction. CONCLUSIONS: In this setting we could not show benefit of an interdisciplinary stroke team supporting patients at discharge perhaps because standard aftercare was very efficient already....

  1. Development and Validation of a Predictive Model for Functional Outcome After Stroke Rehabilitation: The Maugeri Model.

    Science.gov (United States)

    Scrutinio, Domenico; Lanzillo, Bernardo; Guida, Pietro; Mastropasqua, Filippo; Monitillo, Vincenzo; Pusineri, Monica; Formica, Roberto; Russo, Giovanna; Guarnaschelli, Caterina; Ferretti, Chiara; Calabrese, Gianluigi

    2017-12-01

    Prediction of outcome after stroke rehabilitation may help clinicians in decision-making and planning rehabilitation care. We developed and validated a predictive tool to estimate the probability of achieving improvement in physical functioning (model 1) and a level of independence requiring no more than supervision (model 2) after stroke rehabilitation. The models were derived from 717 patients admitted for stroke rehabilitation. We used multivariable logistic regression analysis to build each model. Then, each model was prospectively validated in 875 patients. Model 1 included age, time from stroke occurrence to rehabilitation admission, admission motor and cognitive Functional Independence Measure scores, and neglect. Model 2 included age, male gender, time since stroke onset, and admission motor and cognitive Functional Independence Measure score. Both models demonstrated excellent discrimination. In the derivation cohort, the area under the curve was 0.883 (95% confidence intervals, 0.858-0.910) for model 1 and 0.913 (95% confidence intervals, 0.884-0.942) for model 2. The Hosmer-Lemeshow χ 2 was 4.12 ( P =0.249) and 1.20 ( P =0.754), respectively. In the validation cohort, the area under the curve was 0.866 (95% confidence intervals, 0.840-0.892) for model 1 and 0.850 (95% confidence intervals, 0.815-0.885) for model 2. The Hosmer-Lemeshow χ 2 was 8.86 ( P =0.115) and 34.50 ( P =0.001), respectively. Both improvement in physical functioning (hazard ratios, 0.43; 0.25-0.71; P =0.001) and a level of independence requiring no more than supervision (hazard ratios, 0.32; 0.14-0.68; P =0.004) were independently associated with improved 4-year survival. A calculator is freely available for download at https://goo.gl/fEAp81. This study provides researchers and clinicians with an easy-to-use, accurate, and validated predictive tool for potential application in rehabilitation research and stroke management. © 2017 American Heart Association, Inc.

  2. Trans-sodium crocetinate improves outcomes in rodent models of occlusive and hemorrhagic stroke.

    Science.gov (United States)

    Wang, Yi; Yoshimura, Ryo; Manabe, Hiroaki; Schretter, Catherine; Clarke, Ryon; Cai, Yu; Fitzgerald, Mark; Lee, Kevin S

    2014-10-02

    Trans-sodium crocetinate (TSC) is a novel carotenoid compound capable of enhancing the diffusion of small molecules in aqueous solutions. TSC improves the diffusion of oxygen and glucose, and increases oxygenation in ischemic brain tissue. TSC also dampens the intensity of an ischemic challenge during an ongoing ischemic event. The current study examined the impact of TSC in rat models of ischemic and hemorrhagic stroke. Rat three vessel occlusion (3VO), and combined 3VO and one vessel occlusion (3VO/1VO) models of ischemic stroke were evaluated for structural and behavioral outcomes. The effects of TSC were also tested in a rat model of intracerebral hemorrhage (ICH). Delayed treatment with TSC reduced infarct volume in a rodent model of transient focal ischemia involving either 2 or 6h of ischemia. Neurological outcomes, based on a multi-scale assessment and automated gait analysis, also were improved by TSC treatment. Additionally, TSC reduced edema and hemorrhagic volume in a rat model of ICH. An optimal therapeutic candidate for early intervention in ischemic stroke should be effective when administered on a delayed basis and should not aggravate outcomes associated with hemorrhagic stroke. The current findings demonstrate that delayed TSC treatment improves outcomes in experimental models of both ischemic and hemorrhagic stroke. Together, these findings suggest that TSC may be a safe and beneficial therapeutic modality for early stroke intervention, irrespective of the type of stroke involved. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Animation of 3D Model of Human Head

    Directory of Open Access Journals (Sweden)

    V. Michalcin

    2007-04-01

    Full Text Available The paper deals with the new algorithm of animation of 3D model of the human head in combination with its global motion. The designed algorithm is very fast and with low calculation requirements, because it does not need the synthesis of the input videosequence for estimation of the animation parameters as well as the parameters of global motion. The used 3D model Candide generates different expressions using its animation units which are controlled by the animation parameters. These ones are estimated on the basis of optical flow without the need of extracting of the feature points in the frames of the input videosequence because they are given by the selected vertices of the animation units of the calibrated 3D model Candide. The established multiple iterations inside the designed animation algorithm of 3D model of the human head between two successive frames significantly improved its accuracy above all for the large motion.

  4. MODELING OF ANIMATED SIMULATIONS BY MAXIMA PROGRAM TOOLS

    Directory of Open Access Journals (Sweden)

    Nataliya O. Bugayets

    2015-06-01

    Full Text Available The article deals with the methodical features in training of computer simulation of systems and processes using animation. In the article the importance of visibility of educational material that combines sensory and thinking sides of cognition is noted. The concept of modeling and the process of building models has been revealed. Attention is paid to the development of skills that are essential for effective learning of animated simulation by visual aids. The graphical environment tools of the computer mathematics system Maxima for animated simulation are described. The examples of creation of models animated visual aids and their use for the development of research skills are presented.

  5. Animal Models of Compulsive Eating Behavior

    OpenAIRE

    Matteo Di Segni; Enrico Patrono; Loris Patella; Stefano Puglisi-Allegra; Rossella Ventura

    2014-01-01

    Eating disorders are multifactorial conditions that can involve a combination of genetic, metabolic, environmental, and behavioral factors. Studies in humans and laboratory animals show that eating can also be regulated by factors unrelated to metabolic control. Several studies suggest a link between stress, access to highly palatable food, and eating disorders. Eating “comfort foods” in response to a negative emotional state, for example, suggests that some individuals overeat to self-medica...

  6. The Use of Animal Models in Behavioural Neuroscience Research

    NARCIS (Netherlands)

    Bovenkerk, B.; Kaldewaij, F.

    2015-01-01

    Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are

  7. The Use of Animal Models in Behavioural Neuroscience Research.

    NARCIS (Netherlands)

    Bovenkerk, Bernice; Kaldewaij, Frederike

    2015-01-01

    Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are

  8. Stress and adaptation : Toward ecologically relevant animal models

    NARCIS (Netherlands)

    Koolhaas, Jaap M.; Boer, Sietse F. de; Buwalda, Bauke

    Animal models have contributed considerably to the current understanding of mechanisms underlying the role of stress in health and disease. Despite the progress made already, much more can be made by more carefully exploiting animals' and humans' shared biology, using ecologically relevant models.

  9. Aspects of animal models for major neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Lefter Radu

    2014-01-01

    Full Text Available We will review the main animal models for the major neuropsychiatric disorders, focusing on schizophrenia, Alzheimer’s disease, Parkinson’s disease, depression, anxiety and autism. Although these mental disorders are specifically human pathologies and therefore impossible to perfectly replicate in animals, the use of experimental animals is based on the physiological and anatomical similarities between humans and animals such as the rat, and mouse, and on the fact that 99% of human and murine genomes are shared. Pathological conditions in animals can be assessed by manipulating the metabolism of neurotransmitters, through various behavioral tests, and by determining biochemical parameters that can serve as important markers of disorders.

  10. Decision-tree model of treatment-seeking behaviors after detecting symptoms by Korean stroke patients.

    Science.gov (United States)

    Oh, Hyo-Sook; Park, Hyeoun-Ae

    2006-06-01

    This study was performed to develop and test a decision-tree model of treatment-seeking behaviors about when Korean patients visit a doctor after experiencing stroke symptoms. The study used methodological triangulation. The model was developed based on qualitative data collected from in-depth interviews with 18 stroke patients. The model was tested using quantitative data collected from interviews and a structured questionnaire involving 150 stroke patients. The predictability of the decision-tree model was quantified as the proportion of participants who followed the pathway predicted by the model. Decision outcomes of the model were categorized into immediate and delayed treatment-seeking behavior. The model was influenced by lowered consciousness, social-group influences, perceived seriousness of symptoms, past history of hypertension or stroke, and barriers to hospital visits. The predictability of the model was found to be 90.7%. The results from this study can help healthcare personnel understand the education needs of stroke patients regarding treatment-seeking behaviors, and hence aid in the development of educational strategies for stroke patients.

  11. Structure constants of the OSP(1 vertical stroke 2) WZNW model

    Energy Technology Data Exchange (ETDEWEB)

    Hikida, Y.; Schomerus, V.

    2007-11-15

    We propose exact formulas for the 2- and 3-point functions of the WZNW model on the non-compact supergroup OSP(1 vertical stroke 2). Using the path integral approach that was recently developed in arXiv:0706.1030 we show how local correlation functions in the OSP(p vertical stroke 2) WZNW models can be obtained from those of N=p supersymmetric Liouville field theory for p=1,2. We then employ known results on correlators in N=1 Liouville theory to determine the structure constants of the OSP(1 vertical stroke 2) theory. (orig.)

  12. Formal models in animal-metacognition research: the problem of interpreting animals' behavior.

    Science.gov (United States)

    Smith, J David; Zakrzewski, Alexandria C; Church, Barbara A

    2016-10-01

    Ongoing research explores whether animals have precursors to metacognition-that is, the capacity to monitor mental states or cognitive processes. Comparative psychologists have tested apes, monkeys, rats, pigeons, and a dolphin using perceptual, memory, foraging, and information-seeking paradigms. The consensus is that some species have a functional analog to human metacognition. Recently, though, associative modelers have used formal-mathematical models hoping to describe animals' "metacognitive" performances in associative-behaviorist ways. We evaluate these attempts to reify formal models as proof of particular explanations of animal cognition. These attempts misunderstand the content and proper application of models. They embody mistakes of scientific reasoning. They blur fundamental distinctions in understanding animal cognition. They impede theoretical development. In contrast, an energetic empirical enterprise is achieving strong success in describing the psychology underlying animals' metacognitive performances. We argue that this careful empirical work is the clear path to useful theoretical development. The issues raised here about formal modeling-in the domain of animal metacognition-potentially extend to biobehavioral research more broadly.

  13. Geographic Modeling to Quantify the Impact of Primary and Comprehensive Stroke Center Destination Policies.

    Science.gov (United States)

    Mullen, Michael T; Pajerowski, William; Messé, Steven R; Mechem, C Crawford; Jia, Judy; Abboud, Michael; David, Guy; Carr, Brendan G; Band, Roger

    2018-02-28

    We evaluated the impact of a primary stroke center (PSC) destination policy in a major metropolitan city and used geographic modeling to evaluate expected changes for a comprehensive stroke center policy. We identified suspected stroke emergency medical services encounters from 1/1/2004 to 12/31/2013 in Philadelphia, PA. Transport times were compared before and after initiation of a PSC destination policy on 10/3/2011. Geographic modeling estimated the impact of bypassing the closest hospital for the closest PSC and for the closest comprehensive stroke center. There were 2 326 943 emergency medical services runs during the study period, of which 15 099 had a provider diagnosis of stroke. Bypassing the closest hospital for a PSC was common before the official policy and increased steadily over time. Geographic modeling suggested that bypassing the closest hospital in favor of the closest PSC adds a median of 3.1 minutes to transport time. Bypassing to the closest comprehensive stroke center would add a median of 8.3 minutes. Within a large metropolitan area, the time cost of routing patients preferentially to PSCs and comprehensive stroke centers is low. © 2018 American Heart Association, Inc.

  14. Validation of simplified centre of mass models during gait in individuals with chronic stroke.

    Science.gov (United States)

    Huntley, Andrew H; Schinkel-Ivy, Alison; Aqui, Anthony; Mansfield, Avril

    2017-10-01

    The feasibility of using a multiple segment (full-body) kinematic model in clinical gait assessment is difficult when considering obstacles such as time and cost constraints. While simplified gait models have been explored in healthy individuals, no such work to date has been conducted in a stroke population. The aim of this study was to quantify the errors of simplified kinematic models for chronic stroke gait assessment. Sixteen individuals with chronic stroke (>6months), outfitted with full body kinematic markers, performed a series of gait trials. Three centre of mass models were computed: (i) 13-segment whole-body model, (ii) 3 segment head-trunk-pelvis model, and (iii) 1 segment pelvis model. Root mean squared error differences were compared between models, along with correlations to measures of stroke severity. Error differences revealed that, while both models were similar in the mediolateral direction, the head-trunk-pelvis model had less error in the anteroposterior direction and the pelvis model had less error in the vertical direction. There was some evidence that the head-trunk-pelvis model error is influenced in the mediolateral direction for individuals with more severe strokes, as a few significant correlations were observed between the head-trunk-pelvis model and measures of stroke severity. These findings demonstrate the utility and robustness of the pelvis model for clinical gait assessment in individuals with chronic stroke. Low error in the mediolateral and vertical directions is especially important when considering potential stability analyses during gait for this population, as lateral stability has been previously linked to fall risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Animal models for microbicide safety and efficacy testing.

    Science.gov (United States)

    Veazey, Ronald S

    2013-07-01

    Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

  16. Rat middle cerebral artery occlusion is not a suitable model for the study of stroke-induced spontaneous infections.

    Directory of Open Access Journals (Sweden)

    Mireia Campos-Martorell

    Full Text Available BACKGROUND: Infections related to stroke-induced immunodepression are an important complication causing a high rate of death in patients. Several experimental studies in mouse stroke models have described this process but it has never been tested in other species such as rats. METHODS: Our study focused on the appearance of secondary systemic and pulmonary infections in ischemic rats, comparing with sham and naive animals. For that purpose, male Wistar rats were subjected to embolic middle cerebral artery occlusion (eMCAO or to transient MCAO (tMCAO inserting a nylon filament. Forty-eight hours after ischemia, blood and lung samples were evaluated. RESULTS: In eMCAO set, ischemic rats showed a significant decrease in blood-peripheral lymphocytes (naive = 58.8±18.1%, ischemic = 22.9±16.4% together with an increase in polymorphonuclears (PMNs (naive = 29.2±14.7%, ischemic = 71.7±19.5%, while no change in monocytes was observed. The increase in PMNs counts was positively correlated with worse neurological outcome 48 hours after eMCAO (r = 0.55, p = 0.043. However, sham animals showed similar changes in peripheral leukocytes as those seen in ischemic rats (lymphocytes: 40.1±19.7%; PMNs: 51.7±19.2%. Analysis of bacteriological lung growth showed clear differences between naive (0±0 CFU/mL; log10 and both sham (3.9±2.5 CFU/mL; log10 and ischemic (4.3±2.9 CFU/mL; log10 groups. Additionally, naive animals presented non-pathological lung histology, while both sham and ischemic showed congestion, edema or hemorrhage. Concordant results were found in the second set of animals submitted to a tMCAO. CONCLUSIONS: Inflammatory and infection changes in Wistar rats subjected to MCAO models may be attributed not only to the brain ischemic injury but to the surgical aggression and/or anaesthetic stress. Consequently, we suggest that stroke-induced immunodepression in ischemic experimental models should be interpreted with caution

  17. Mathematical models of behavior of individual animals.

    Science.gov (United States)

    Tsibulsky, Vladimir L; Norman, Andrew B

    2007-01-01

    This review is focused on mathematical modeling of behaviors of a whole organism with special emphasis on models with a clearly scientific approach to the problem that helps to understand the mechanisms underlying behavior. The aim is to provide an overview of old and contemporary mathematical models without complex mathematical details. Only deterministic and stochastic, but not statistical models are reviewed. All mathematical models of behavior can be divided into two main classes. First, models that are based on the principle of teleological determinism assume that subjects choose the behavior that will lead them to a better payoff in the future. Examples are game theories and operant behavior models both of which are based on the matching law. The second class of models are based on the principle of causal determinism, which assume that subjects do not choose from a set of possibilities but rather are compelled to perform a predetermined behavior in response to specific stimuli. Examples are perception and discrimination models, drug effects models and individual-based population models. A brief overview of the utility of each mathematical model is provided for each section.

  18. Systematic reviews of animal models: methodology versus epistemology.

    Science.gov (United States)

    Greek, Ray; Menache, Andre

    2013-01-01

    Systematic reviews are currently favored methods of evaluating research in order to reach conclusions regarding medical practice. The need for such reviews is necessitated by the fact that no research is perfect and experts are prone to bias. By combining many studies that fulfill specific criteria, one hopes that the strengths can be multiplied and thus reliable conclusions attained. Potential flaws in this process include the assumptions that underlie the research under examination. If the assumptions, or axioms, upon which the research studies are based, are untenable either scientifically or logically, then the results must be highly suspect regardless of the otherwise high quality of the studies or the systematic reviews. We outline recent criticisms of animal-based research, namely that animal models are failing to predict human responses. It is this failure that is purportedly being corrected via systematic reviews. We then examine the assumption that animal models can predict human outcomes to perturbations such as disease or drugs, even under the best of circumstances. We examine the use of animal models in light of empirical evidence comparing human outcomes to those from animal models, complexity theory, and evolutionary biology. We conclude that even if legitimate criticisms of animal models were addressed, through standardization of protocols and systematic reviews, the animal model would still fail as a predictive modality for human response to drugs and disease. Therefore, systematic reviews and meta-analyses of animal-based research are poor tools for attempting to reach conclusions regarding human interventions.

  19. Animal Models of Hemophilia and Related Bleeding Disorders

    Science.gov (United States)

    Lozier, Jay N.; Nichols, Timothy C.

    2013-01-01

    Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467

  20. Time series sightability modeling of animal populations.

    Directory of Open Access Journals (Sweden)

    Althea A ArchMiller

    Full Text Available Logistic regression models-or "sightability models"-fit to detection/non-detection data from marked individuals are often used to adjust for visibility bias in later detection-only surveys, with population abundance estimated using a modified Horvitz-Thompson (mHT estimator. More recently, a model-based alternative for analyzing combined detection/non-detection and detection-only data was developed. This approach seemed promising, since it resulted in similar estimates as the mHT when applied to data from moose (Alces alces surveys in Minnesota. More importantly, it provided a framework for developing flexible models for analyzing multiyear detection-only survey data in combination with detection/non-detection data. During initial attempts to extend the model-based approach to multiple years of detection-only data, we found that estimates of detection probabilities and population abundance were sensitive to the amount of detection-only data included in the combined (detection/non-detection and detection-only analysis. Subsequently, we developed a robust hierarchical modeling approach where sightability model parameters are informed only by the detection/non-detection data, and we used this approach to fit a fixed-effects model (FE model with year-specific parameters and a temporally-smoothed model (TS model that shares information across years via random effects and a temporal spline. The abundance estimates from the TS model were more precise, with decreased interannual variability relative to the FE model and mHT abundance estimates, illustrating the potential benefits from model-based approaches that allow information to be shared across years.

  1. Reviewing model application to support animal health decision making.

    Science.gov (United States)

    Singer, Alexander; Salman, Mo; Thulke, Hans-Hermann

    2011-04-01

    Animal health is of societal importance as it affects human welfare, and anthropogenic interests shape decision making to assure animal health. Scientific advice to support decision making is manifold. Modelling, as one piece of the scientific toolbox, is appreciated for its ability to describe and structure data, to give insight in complex processes and to predict future outcome. In this paper we study the application of scientific modelling to support practical animal health decisions. We reviewed the 35 animal health related scientific opinions adopted by the Animal Health and Animal Welfare Panel of the European Food Safety Authority (EFSA). Thirteen of these documents were based on the application of models. The review took two viewpoints, the decision maker's need and the modeller's approach. In the reviewed material three types of modelling questions were addressed by four specific model types. The correspondence between tasks and models underpinned the importance of the modelling question in triggering the modelling approach. End point quantifications were the dominating request from decision makers, implying that prediction of risk is a major need. However, due to knowledge gaps corresponding modelling studies often shed away from providing exact numbers. Instead, comparative scenario analyses were performed, furthering the understanding of the decision problem and effects of alternative management options. In conclusion, the most adequate scientific support for decision making - including available modelling capacity - might be expected if the required advice is clearly stated. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Time series sightability modeling of animal populations

    Science.gov (United States)

    ArchMiller, Althea A.; Dorazio, Robert; St. Clair, Katherine; Fieberg, John R.

    2018-01-01

    Logistic regression models—or “sightability models”—fit to detection/non-detection data from marked individuals are often used to adjust for visibility bias in later detection-only surveys, with population abundance estimated using a modified Horvitz-Thompson (mHT) estimator. More recently, a model-based alternative for analyzing combined detection/non-detection and detection-only data was developed. This approach seemed promising, since it resulted in similar estimates as the mHT when applied to data from moose (Alces alces) surveys in Minnesota. More importantly, it provided a framework for developing flexible models for analyzing multiyear detection-only survey data in combination with detection/non-detection data. During initial attempts to extend the model-based approach to multiple years of detection-only data, we found that estimates of detection probabilities and population abundance were sensitive to the amount of detection-only data included in the combined (detection/non-detection and detection-only) analysis. Subsequently, we developed a robust hierarchical modeling approach where sightability model parameters are informed only by the detection/non-detection data, and we used this approach to fit a fixed-effects model (FE model) with year-specific parameters and a temporally-smoothed model (TS model) that shares information across years via random effects and a temporal spline. The abundance estimates from the TS model were more precise, with decreased interannual variability relative to the FE model and mHT abundance estimates, illustrating the potential benefits from model-based approaches that allow information to be shared across years.

  3. Animal models for dengue vaccine development and testing.

    Science.gov (United States)

    Na, Woonsung; Yeom, Minjoo; Choi, Il-Kyu; Yook, Heejun; Song, Daesub

    2017-07-01

    Dengue fever is a tropical endemic disease; however, because of climate change, it may become a problem in South Korea in the near future. Research on vaccines for dengue fever and outbreak preparedness are currently insufficient. In addition, because there are no appropriate animal models, controversial results from vaccine efficacy assessments and clinical trials have been reported. Therefore, to study the mechanism of dengue fever and test the immunogenicity of vaccines, an appropriate animal model is urgently needed. In addition to mouse models, more suitable models using animals that can be humanized will need to be constructed. In this report, we look at the current status of model animal construction and discuss which models require further development.

  4. Animals

    International Nuclear Information System (INIS)

    Skuterud, L.; Strand, P.; Howard, B.J.

    1997-01-01

    The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG)

  5. Recent advances in animal model experimentation in autism research.

    Science.gov (United States)

    Tania, Mousumi; Khan, Md Asaduzzaman; Xia, Kun

    2014-10-01

    Autism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism. We have reviewed the publications over the last three decades, which are related to animal model study in autism. Animal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism. In this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.

  6. Animal models for human genetic diseases

    African Journals Online (AJOL)

    Sharif Sons

    to be the prime model of inherited human disease and share 99% of their ... disturbances (including anxiety and depression) ..... Leibovici M, Safieddine S, Petit C (2008). Mouse models for human hereditary deafness. Curr. Top. Dev. Biol. 84:385-429. Levi YF, Meiner Z, Canello T, Frid K, Kovacs GG, Budka H, Avrahami.

  7. Research progress on animal models of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Wen DONG

    2015-08-01

    Full Text Available Alzheimer's disease (AD is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

  8. The Effects of Various Weather Conditions as a Potential Ischemic Stroke Trigger in Dogs.

    Science.gov (United States)

    Meadows, Kristy L; Silver, Gena M

    2017-11-16

    Stroke is the fifth leading cause of death in the United States, and is the leading cause of serious, long-term disability worldwide. There are at least 795,000 new or recurrent strokes each year, and approximately 85% of all stroke occurrences are ischemic. Unfortunately, companion animals are also at risk for ischemic stroke. Although the exact incidence of ischemic stroke in companion animals is unknown, some studies, and the veterinary information network (VIN), report that approximately 3% of neurological case referrals are due to a stroke. There is a long list of predisposing factors associated with the risk of ischemic stroke in both humans and canines; however, these factors do not explain why a stroke happens at a particular time on a particular day. Our understanding of these potential stroke "triggers" is limited, and the effect of transient environmental exposures may be one such "trigger". The present study investigated the extent to which the natural occurrence of canine ischemic stroke was related to the weather conditions in the time-period immediately preceding the onset of stroke. The results of the present study demonstrated that the change in weather conditions could be a potential stroke trigger, with the strokes evaluated occurring after periods of rapid, large fluctuations in weather conditions. There are currently no epidemiological data on the seasonal variability of ischemic stroke in dogs, and determining whether canine stroke parallels human stroke would further validate the use of companion dogs as an appropriate naturally occurring model.

  9. A Comparison of Different Engineering Models for Computation of Lightning Magnetic Field of Negative First Strokes

    Directory of Open Access Journals (Sweden)

    V. Javor

    2012-11-01

    Full Text Available A comparison of different engineering models results for a lightning magnetic field of negative first strokes is presented in this paper. A new function for representing double-peaked channel-base current is used for lightning stroke modeling. This function includes the initial and subsidiary peak in a current waveform. For experimentally measured currents, a magnetic field is calculated for the three engineering models: transmission line (TL model, TL model with linear decay (MTLL, and TL model with exponential decay (MTLE.

  10. Animal Models and Antifungal Agents in Paracoccidioidomycosis: An Overview.

    Science.gov (United States)

    Goldani, Luciano Z; Wirth, Fernanda

    2017-08-01

    Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America. The morbidity and mortality associated with paracoccidioidomycosis necessitate our understanding of fungal pathogenesis and discovering of new agents to treat this infection. Animal models have contributed much to the knowledge of fungal infections and their corresponding therapeutic treatments. This is true for animal models of the primary fungal pathogens such as P. brasiliensis. This review describes the development, details and utility of animal models of paracoccidioidomycosis for studying and developing the current antifungal agents used for therapy of this fungal disease and novel agents with antifungal properties against P. brasiliensis.

  11. Epidemiological models to support animal disease surveillance activities

    DEFF Research Database (Denmark)

    Willeberg, Preben; Paisley, Larry; Lind, Peter

    2011-01-01

    Epidemiological models have been used extensively as a tool in improving animal disease surveillance activities. A review of published papers identified three main groups of model applications: models for planning surveillance, models for evaluating the performance of surveillance systems...... and models for interpreting surveillance data as part of ongoing control or eradication programmes. Two Danish examples are outlined. The first illustrates how models were used in documenting country freedom from disease (trichinellosis) and the second demonstrates how models were of assistance in predicting...

  12. Animal models for periodontal regeneration and peri-implant responses.

    Science.gov (United States)

    Kantarci, Alpdogan; Hasturk, Hatice; Van Dyke, Thomas E

    2015-06-01

    Translation of experimental data to the clinical setting requires the safety and efficacy of such data to be confirmed in animal systems before application in humans. In dental research, the animal species used is dependent largely on the research question or on the disease model. Periodontal disease and, by analogy, peri-implant disease, are complex infections that result in a tissue-degrading inflammatory response. It is impossible to explore the complex pathogenesis of periodontitis or peri-implantitis using only reductionist in-vitro methods. Both the disease process and healing of the periodontal and peri-implant tissues can be studied in animals. Regeneration (after periodontal surgery), in response to various biologic materials with potential for tissue engineering, is a continuous process involving various types of tissue, including epithelia, connective tissues and alveolar bone. The same principles apply to peri-implant healing. Given the complexity of the biology, animal models are necessary and serve as the standard for successful translation of regenerative materials and dental implants to the clinical setting. Smaller species of animal are more convenient for disease-associated research, whereas larger animals are more appropriate for studies that target tissue healing as the anatomy of larger animals more closely resembles human dento-alveolar architecture. This review focuses on the animal models available for the study of regeneration in periodontal research and implantology; the advantages and disadvantages of each animal model; the interpretation of data acquired; and future perspectives of animal research, with a discussion of possible nonanimal alternatives. Power calculations in such studies are crucial in order to use a sample size that is large enough to generate statistically useful data, whilst, at the same time, small enough to prevent the unnecessary use of animals. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. A unified engineering model of the first stroke in downward negative lightning

    Science.gov (United States)

    Nag, Amitabh; Rakov, Vladimir A.

    2016-03-01

    Each stroke in a negative cloud-to-ground lightning flash is composed of downward leader and upward return stroke processes, which are usually modeled individually. The first stroke leader is stepped and starts with preliminary breakdown (PB) which is often viewed as a separate process. We present the first unified engineering model for computing the electric field produced by a sequence of PB, stepped leader, and return stroke processes, serving to transport negative charge to ground. We assume that a negatively charged channel extends downward in a stepped fashion during both the PB and leader stages. Each step involves a current wave that propagates upward along the newly formed channel section. Once the leader attaches to ground, an upward propagating return stroke neutralizes the charge deposited along the channel. Model-predicted electric fields are in reasonably good agreement with simultaneous measurements at both near (hundreds of meters, electrostatic field component is dominant) and far (tens of kilometers, radiation field component is dominant) distances from the lightning channel. Relations between the features of computed electric field waveforms and model input parameters are examined. It appears that peak currents associated with PB pulses are similar to return stroke peak currents, and the observed variation of electric radiation field peaks produced by leader steps at different heights above ground is influenced by the ground corona space charge.

  14. Application of Model Animals in the Study of Drug Toxicology

    Science.gov (United States)

    Song, Yagang; Miao, Mingsan

    2018-01-01

    Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

  15. Animal models for testing anti-prion drugs.

    Science.gov (United States)

    Fernández-Borges, Natalia; Elezgarai, Saioa R; Eraña, Hasier; Castilla, Joaquín

    2013-01-01

    Prion diseases belong to a group of fatal infectious diseases with no effective therapies available. Throughout the last 35 years, less than 50 different drugs have been tested in different experimental animal models without hopeful results. An important limitation when searching for new drugs is the existence of appropriate models of the disease. The three different possible origins of prion diseases require the existence of different animal models for testing anti-prion compounds. Wild type, over-expressing transgenic mice and other more sophisticated animal models have been used to evaluate a diversity of compounds which some of them were previously tested in different in vitro experimental models. The complexity of prion diseases will require more pre-screening studies, reliable sporadic (or spontaneous) animal models and accurate chemical modifications of the selected compounds before having an effective therapy against human prion diseases. This review is intended to put on display the more relevant animal models that have been used in the search of new antiprion therapies and describe some possible procedures when handling chemical compounds presumed to have anti-prion activity prior to testing them in animal models.

  16. Medulloblastoma: Molecular Genetics and Animal Models

    Directory of Open Access Journals (Sweden)

    Corey Raffel

    2004-07-01

    Full Text Available Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.

  17. Modeling animal movements using stochastic differential equations

    Science.gov (United States)

    Haiganoush K. Preisler; Alan A. Ager; Bruce K. Johnson; John G. Kie

    2004-01-01

    We describe the use of bivariate stochastic differential equations (SDE) for modeling movements of 216 radiocollared female Rocky Mountain elk at the Starkey Experimental Forest and Range in northeastern Oregon. Spatially and temporally explicit vector fields were estimated using approximating difference equations and nonparametric regression techniques. Estimated...

  18. Animal models of substance abuse and addiction: implications for science, animal welfare, and society.

    Science.gov (United States)

    Lynch, Wendy J; Nicholson, Katherine L; Dance, Mario E; Morgan, Richard W; Foley, Patricia L

    2010-06-01

    Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models.

  19. Animals

    Energy Technology Data Exchange (ETDEWEB)

    Skuterud, L.; Strand, P. [Norwegian Radiation Protection Authority (Norway); Howard, B.J. [Inst. of Terrestrial Ecology (United Kingdom)

    1997-10-01

    The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG). 68 refs.

  20. Advances in Animal Models of Hepatitis B Virus Infection

    Directory of Open Access Journals (Sweden)

    Zhang Hang

    2015-12-01

    Full Text Available Hepatitis B virus (HBV infection seriously affects human health. Stable and reliable animal models of HBV infection bear significance in studying pathogenesis of this health condition and development of intervention measures. HBV exhibits high specificity for hosts, and chimpanzee is long used as sole animal model of HBV infection. However, use of chimpanzees is strictly constrained because of ethical reasons. Many methods were used to establish small-animal models of HBV infection. Tupaia is the only nonprimate animal that can be infected by HBV. Use of HBV-related duck hepatitis virus and marmot hepatitis virus infection model contributed to evaluation of mechanism of HBV replication and HBV treatment methods. In recent years, development of human–mouse chimeric model provided possibility of using common experimental animals to carry out HBV research. These models feature their own advantages and disadvantages and can be complementary in some ways. This study provides an overview of current and commonly used animal models of HBV infection.

  1. Animal models for evaluation of oral delivery of biopharmaceuticals

    DEFF Research Database (Denmark)

    Harloff-Helleberg, Stine; Nielsen, Line Hagner; Nielsen, Hanne Mørck

    2017-01-01

    of systems for oral delivery of biopharmaceuticals may result in new treatment modalities to increase the patient compliance and reduce product cost. In the preclinical development phase, use of experimental animal models is essential for evaluation of new formulation designs. In general, the limited oral...... bioavailability of biopharmaceuticals, of just a few percent, is expected, and therefore, the animal models and the experimental settings must be chosen with utmost care. More knowledge and focus on this topic is highly needed, despite experience from the numerous studies evaluating animal models for oral drug...... delivery of small molecule drugs. This review highlights and discusses pros and cons of the most currently used animal models and settings. Additionally, it also looks into the influence of anesthetics and sampling methods for evaluation of drug delivery systems for oral delivery of biopharmaceuticals...

  2. Albino mice as an animal model for infantile nystagmus syndrome

    NARCIS (Netherlands)

    D.L. Traber (Daniel); C.-C. Chen (Chien-Cheng); Y.-Y. Huang (Ying-Yu); M. Spoor (Monique); J. Roos (Jeanine); M.A. Frens (Maarten); D. Straumann (Dominik); C. Grimm (Christian)

    2012-01-01

    textabstractPURPOSE. Individuals with oculocutaneous albinism are predisposed to visual system abnormalities affecting the retina and retinofugal projections, which may lead to reduced visual acuity and Infantile Nystagmus Syndrome (INS). Due to absence of an established mammalian animal model,

  3. Instrumental and ethical aspects of experimental research with animal models

    Directory of Open Access Journals (Sweden)

    Mirian Watanabe

    2014-02-01

    Full Text Available Experimental animal models offer possibilities of physiology knowledge, pathogenesis of disease and action of drugs that are directly related to quality nursing care. This integrative review describes the current state of the instrumental and ethical aspects of experimental research with animal models, including the main recommendations of ethics committees that focus on animal welfare and raises questions about the impact of their findings in nursing care. Data show that, in Brazil, the progress in ethics for the use of animals for scientific purposes was consolidated with Law No. 11.794/2008 establishing ethical procedures, attending health, genetic and experimental parameters. The application of ethics in handling of animals for scientific and educational purposes and obtaining consistent and quality data brings unquestionable contributions to the nurse, as they offer subsidies to relate pathophysiological mechanisms and the clinical aspect on the patient.

  4. Biology of Obesity: Lessons from Animal Models of Obesity

    Directory of Open Access Journals (Sweden)

    Keizo Kanasaki

    2011-01-01

    problems, including diabetes, cardiovascular disease, respiratory failure, muscle weakness, and cancer. The precise molecular mechanisms by which obesity induces these health problems are not yet clear. To better understand the pathomechanisms of human disease, good animal models are essential. In this paper, we will analyze animal models of obesity and their use in the research of obesity-associated human health conditions and diseases such as diabetes, cancer, and obstructive sleep apnea syndrome.

  5. Stop staring facial modeling and animation done right

    CERN Document Server

    Osipa, Jason

    2010-01-01

    The de facto official source on facial animation—now updated!. If you want to do character facial modeling and animation at the high levels achieved in today's films and games, Stop Staring: Facial Modeling and Animation Done Right, Third Edition , is for you. While thoroughly covering the basics such as squash and stretch, lip syncs, and much more, this new edition has been thoroughly updated to capture the very newest professional design techniques, as well as changes in software, including using Python to automate tasks.: Shows you how to create facial animation for movies, games, and more;

  6. Technical Note: How to use Winbugs to infer animal models

    DEFF Research Database (Denmark)

    Damgaard, Lars Holm

    2007-01-01

    This paper deals with Bayesian inferences of animal models using Gibbs sampling. First, we suggest a general and efficient method for updating additive genetic effects, in which the computational cost is independent of the pedigree depth and increases linearly only with the size of the pedigree. ...... having Student's t distributions. In conclusion, Winbugs can be used to make inferences in small-sized, quantitative, genetic data sets applying a wide range of animal models that are not yet standard in the animal breeding literature...

  7. Reflected stochastic differential equation models for constrained animal movement

    Science.gov (United States)

    Hanks, Ephraim M.; Johnson, Devin S.; Hooten, Mevin B.

    2017-01-01

    Movement for many animal species is constrained in space by barriers such as rivers, shorelines, or impassable cliffs. We develop an approach for modeling animal movement constrained in space by considering a class of constrained stochastic processes, reflected stochastic differential equations. Our approach generalizes existing methods for modeling unconstrained animal movement. We present methods for simulation and inference based on augmenting the constrained movement path with a latent unconstrained path and illustrate this augmentation with a simulation example and an analysis of telemetry data from a Steller sea lion (Eumatopias jubatus) in southeast Alaska.

  8. Proteomics in farm animals models of human diseases.

    Science.gov (United States)

    Ceciliani, Fabrizio; Restelli, Laura; Lecchi, Cristina

    2014-10-01

    The need to provide in vivo complex environments to understand human diseases strongly relies on the use of animal models, which traditionally include small rodents and rabbits. It is becoming increasingly evident that the few species utilised to date cannot be regarded as universal. There is a great need for new animal species that are naturally endowed with specific features relevant to human diseases. Farm animals, including pigs, cows, sheep and horses, represent a valid alternative to commonly utilised rodent models. There is an ample scope for the application of proteomic techniques in farm animals, and the establishment of several proteomic maps of plasma and tissue has clearly demonstrated that farm animals provide a disease environment that closely resembles that of human diseases. The present review offers a snapshot of how proteomic techniques have been applied to farm animals to improve their use as biomedical models. Focus will be on specific topics of biomedical research in which farm animal models have been characterised through the application of proteomic techniques. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Animal models of pancreatic cancer for drug research.

    Science.gov (United States)

    Kapischke, Matthias; Pries, Alexandra

    2008-10-01

    The operative and conservative results of therapy in pancreatic ductal adenocarcinoma remain appallingly poor. This underlines the demand for further research for effective anticancer drugs. The various animal models remain the essential method for the determination of efficacy of substances during preclinical phase. Unfortunately, most of these tested substances showed a good efficacy in pancreatic carcinoma in the animal model but were not confirmed during the clinical phase. The available literature in PubMed, Medline, Ovid and secondary literature was searched regarding the available animal models for drug testing against pancreatic cancer. The models were analyzed regarding their pros and cons in anticancer drug testing. The different modifications of the orthotopic model (especially in mice) seem at present to be the best model for anticancer testing in pancreatic carcinoma. The value of genetically engineered animal model (GEM) and syngeneic models is on debate. A good selection of the model concerning the questions supposed to be clarified may improve the comparability of the results of animal experiments compared to clinical trials.

  10. MODELING OF ELECTRONIC GASOLINE INJECTION PROCESSES IN TWO STROKE ENGINE

    Directory of Open Access Journals (Sweden)

    Hraivoronskyi, Y.

    2013-06-01

    Full Text Available Basic provision of the processes developed mode, occurring in ignition fuel system with electronically controlled two stroke engine with positive ignition are given. Fuel injection process’ calculation results for the case of placing fuel injector into intake system presented.

  11. Large animal models for vaccine development and testing.

    Science.gov (United States)

    Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A

    2015-01-01

    The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. Animal Models Used to Explore Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

    Lysgaard Poulsen, J; Stubbe, J; Lindholt, J S

    2016-01-01

    OBJECTIVE: Experimental animal models have been used to investigate the formation, development, and progression of abdominal aortic aneurysms (AAAs) for decades. New models are constantly being developed to imitate the mechanisms of human AAAs and to identify treatments that are less risky than...... those used today. However, to the authors' knowledge, there is no model identical to the human AAA. The objective of this systematic review was to assess the different types of animal models used to investigate the development, progression, and treatment of AAA and to highlight their advantages...... and limitations. METHODS: A search protocol was used to perform a systematic literature search of PubMed and Embase. A total of 2,830 records were identified. After selection of the relevant articles, 564 papers on animal AAA models were included. RESULTS: The most common models in rodents, including elastase...

  13. Stroke and Drug Delivery--In Vitro Models of the Ischemic Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Tornabene, Erica; Brodin, Birger

    2016-01-01

    Stroke is a major cause of death and disability worldwide. Both cerebral hypoperfusion and focal cerebral infarcts are caused by a reduction of blood flow to the brain, leading to stroke and subsequent brain damage. At present, only few medical treatments of stroke are available, with the Food...... and Drug Administration-approved tissue plasminogen activator for treatment of acute ischemic stroke being the most prominent example. A large number of potential drug candidates for treatment of ischemic brain tissue have been developed and subsequently failed in clinical trials. A deeper understanding...... of permeation pathways across the barrier in ischemic and postischemic brain endothelium is important for development of new medical treatments. The blood-brain barrier, that is, the endothelial monolayer lining the brain capillaries, changes properties during an ischemic event. In vitro models of the blood-brain...

  14. Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences

    Directory of Open Access Journals (Sweden)

    Gillian M. Lavelle

    2016-01-01

    Full Text Available Cystic fibrosis (CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF.

  15. Cytomegalovirus Antivirals and Development of Improved Animal Models

    Science.gov (United States)

    McGregor, Alistair; Choi, K. Yeon

    2015-01-01

    Introduction Cytomegalovirus (CMV) is a ubiquitous pathogen that establishes a life long asymptomatic infection in healthy individuals. Infection of immunesuppressed individuals causes serious illness. Transplant and AIDS patients are highly susceptible to CMV leading to life threatening end organ disease. Another vulnerable population is the developing fetus in utero, where congenital infection can result in surviving newborns with long term developmental problems. There is no vaccine licensed for CMV and current antivirals suffer from complications associated with prolonged treatment. These include drug toxicity and emergence of resistant strains. There is an obvious need for new antivirals. Candidate intervention strategies are tested in controlled pre-clinical animal models but species specificity of HCMV precludes the direct study of the virus in an animal model. Areas covered This review explores the current status of CMV antivirals and development of new drugs. This includes the use of animal models and the development of new improved models such as humanized animal CMV and bioluminescent imaging of virus in animals in real time. Expert Opinion Various new CMV antivirals are in development, some with greater spectrum of activity against other viruses. Although the greatest need is in the setting of transplant patients there remains an unmet need for a safe antiviral strategy against congenital CMV. This is especially important since an effective CMV vaccine remains an elusive goal. In this capacity greater emphasis should be placed on suitable pre-clinical animal models and greater collaboration between industry and academia. PMID:21883024

  16. Review of Animal Models of Prostate Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Jessica K. Simmons

    2014-06-01

    Full Text Available Prostate cancer bone metastases are associated with a poor prognosis and are considered incurable. Insight into the formation and growth of prostate cancer bone metastasis is required for development of new imaging and therapeutic strategies to combat this devastating disease. Animal models are indispensable in investigating cancer pathogenesis and evaluating therapeutics. Multiple animal models of prostate cancer bone metastasis have been developed, but few effectively model prostatic neoplasms and osteoblastic bone metastases as they occur in men. This review discusses the animal models that have been developed to investigate prostate cancer bone metastasis, with a focus on canine models and also includes human xenograft and rodent models. Adult dogs spontaneously develop benign prostatic hyperplasia and prostate cancer with osteoblastic bone metastases. Large animal models, such as dogs, are needed to develop new molecular imaging tools and effective focal intraprostatic therapy. None of the available models fully reflect the metastatic disease seen in men, although the various models have provided important insight into the metastatic process. As additional models are developed and knowledge from the different models is combined, the molecular mechanisms of prostate cancer bone metastasis can be deciphered and targeted for development of novel therapies and molecular diagnostic imaging.

  17. Sex differences in animal models of psychiatric disorders

    Science.gov (United States)

    Kokras, N; Dalla, C

    2014-01-01

    Psychiatric disorders are characterized by sex differences in their prevalence, symptomatology and treatment response. Animal models have been widely employed for the investigation of the neurobiology of such disorders and the discovery of new treatments. However, mostly male animals have been used in preclinical pharmacological studies. In this review, we highlight the need for the inclusion of both male and female animals in experimental studies aiming at gender-oriented prevention, diagnosis and treatment of psychiatric disorders. We present behavioural findings on sex differences from animal models of depression, anxiety, post-traumatic stress disorder, substance-related disorders, obsessive–compulsive disorder, schizophrenia, bipolar disorder and autism. Moreover, when available, we include studies conducted across different stages of the oestrous cycle. By inspection of the relevant literature, it is obvious that robust sex differences exist in models of all psychiatric disorders. However, many times results are conflicting, and no clear conclusion regarding the direction of sex differences and the effect of the oestrous cycle is drawn. Moreover, there is a lack of considerable amount of studies using psychiatric drugs in both male and female animals, in order to evaluate the differential response between the two sexes. Notably, while in most cases animal models successfully mimic drug response in both sexes, test parameters and treatment-sensitive behavioural indices are not always the same for male and female rodents. Thus, there is an increasing need to validate animal models for both sexes and use standard procedures across different laboratories. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24697577

  18. Animal models for the study of hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Wei-Na Guo

    2018-01-01

    Full Text Available Even with an effective vaccine, an estimated 240 million people are chronically infected with hepatitis B virus (HBV worldwide. Current antiviral therapies, including interferon and nucleot(side analogues, rarely cure chronic hepatitis B. Animal models are very crucial for understanding the pathogenesis of chronic hepatitis B and developing new therapeutic drugs or strategies. HBV can only infect humans and chimpanzees, with the use of chimpanzees in HBV research strongly restricted. Thus, most advances in HBV research have been gained using mouse models with HBV replication or infection or models with HBV-related hepadnaviral infection. This review summarizes the animal models currently available for the study of HBV infection.

  19. Animal models of pulmonary emphysema: a stereologist's perspective

    Directory of Open Access Journals (Sweden)

    H. Fehrenbach

    2006-12-01

    Full Text Available A variety of animal models have been suggested as models of pulmonary emphysema; these are critically discussed in the present article from a stereologist's perspective. In addition, a stereological design for the quantification of experimentally induced emphysema is proposed. On the basis of the widely accepted definition of pulmonary emphysema being an "abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls," quantitative morphology is the only method with which to reliably assess the presence of emphysema. Recognising this, careful inspection of animal models that are based on instillation of elastase, genetic alterations, inhalation of cigarette smoke or induction of apoptosis, reveals that both criteria of emphysema definition were demonstrated in surprisingly few of them. Several aspects are suggested to be critical for the understanding of animal models of human emphysema. For example, genetic models that rely on the inhibition of the formation of alveoli during post-natal alveolarisation should clearly be distinguished from models that rely on the loss of mature alveoli after alveolarisation is complete. Furthermore, inhalation models that are characterised by exposed animals exhibiting a severe loss of body weight should carefully examine the relative contribution of intervention and weight loss, respectively. Models that rely on the exposure of juvenile animals for several weeks or even months should take into account the effects of normal lung growth and ageing. Stereology offers appropriate tools with which to quantify the parameters relevant to assess development and the regeneration of emphysema. Stereologists continue to develop tools that will help ascertain the reliability of established and new models. If inappropriate parameters continue to be used for the evaluation of animal models of emphysema, thinking and resources are likely to be misdirected and the

  20. Elementary of animal model for percutaneous and ocular penetration

    Directory of Open Access Journals (Sweden)

    Kalpesh Chhotalal Ashara

    2016-12-01

    Full Text Available Models of animal are the most appropriate method for assessments of human in-vivo percutaneous and ocular penetrations. Monkey and rodents are used for the same. There are several nuts and bolts of each one, so it is necessary to study each one separately. Monkey, porcine and guinea pig penetration are correlated with that of human skin. The skin of rodents, lupus, pigs, etc. has more penetration properties than human skin. Rabbit, goat and sheep eye are mostly used for ocular penetration. The researcher also used hen’s egg chorioallantoic membrane test for ocular irritation study. The other animals’ cornea, cul-de-sac, eyeballs and prepared corneal epithelial models are very less in practice. Web-based alternative non-animal models are also available instead of animal models too. This article describes characteristics of monkeys, pigs, rats, rabbits, guinea pigs and hairless rodents, HuSki model, Cellophane® membrane, egg membrane, gelatin membrane, animal models for ophthalmic delivery, hen’s egg chorioallantoic membrane test, prepared corneal epithelial models and web-based alternative non-animal database.

  1. Models of 'obesity' in large animals and birds.

    Science.gov (United States)

    Clarke, Iain J

    2008-01-01

    Most laboratory-based research on obesity is carried out in rodents, but there are a number of other interesting models in the animal kingdom that are instructive. This includes domesticated animal species such as pigs and sheep, as well as wild, migrating and hibernating species. Larger animals allow particular experimental manipulations that are not possible in smaller animals and especially useful models have been developed to address issues such as manipulation of fetal development. Although some of the most well-studied models are ruminants, with metabolic control that differs from monogastrics, the general principles of metabolic regulation still pertain. It is possible to obtain much more accurate endocrine profiles in larger animals and this has provided important data in relation to leptin and ghrelin physiology. Genetic models have been created in domesticated animals through selection and these complement those of the laboratory rodent. This short review highlights particular areas of research in domesticated and wild species that expand our knowledge of systems that are important for our understanding of obesity and metabolism.

  2. Animal Models of Diabetic Macrovascular Complications: Key Players in the Development of New Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Suvi E. Heinonen

    2015-01-01

    Full Text Available Diabetes mellitus is a lifelong, incapacitating metabolic disease associated with chronic macrovascular complications (coronary heart disease, stroke, and peripheral vascular disease and microvascular disorders leading to damage of the kidneys (nephropathy and eyes (retinopathy. Based on the current trends, the rising prevalence of diabetes worldwide will lead to increased cardiovascular morbidity and mortality. Therefore, novel means to prevent and treat these complications are needed. Under the auspices of the IMI (Innovative Medicines Initiative, the SUMMIT (SUrrogate markers for Micro- and Macrovascular hard end points for Innovative diabetes Tools consortium is working on the development of novel animal models that better replicate vascular complications of diabetes and on the characterization of the available models. In the past years, with the high level of genomic information available and more advanced molecular tools, a very large number of models has been created. Selecting the right model for a specific study is not a trivial task and will have an impact on the study results and their interpretation. This review gathers information on the available experimental animal models of diabetic macrovascular complications and evaluates their pros and cons for research purposes as well as for drug development.

  3. OBESITY AND CRITICAL ILLNESS: INSIGHTS FROM ANIMAL MODELS.

    Science.gov (United States)

    Mittwede, Peter N; Clemmer, John S; Bergin, Patrick F; Xiang, Lusha

    2016-04-01

    Critical illness is a major cause of morbidity and mortality around the world. While obesity is often detrimental in the context of trauma, it is paradoxically associated with improved outcomes in some septic patients. The reasons for these disparate outcomes are not well understood. A number of animal models have been used to study the obese response to various forms of critical illness. Just as there have been many animal models that have attempted to mimic clinical conditions, there are many clinical scenarios that can occur in the highly heterogeneous critically ill patient population that occupies hospitals and intensive care units. This poses a formidable challenge for clinicians and researchers attempting to understand the mechanisms of disease and develop appropriate therapies and treatment algorithms for specific subsets of patients, including the obese. The development of new, and the modification of existing animal models, is important in order to bring effective treatments to a wide range of patients. Not only do experimental variables need to be matched as closely as possible to clinical scenarios, but animal models with pre-existing comorbid conditions need to be studied. This review briefly summarizes animal models of hemorrhage, blunt trauma, traumatic brain injury, and sepsis. It also discusses what has been learned through the use of obese models to study the pathophysiology of critical illness in light of what has been demonstrated in the clinical literature.

  4. Precise MRI-based stereotaxic surgery in large animal models

    DEFF Research Database (Denmark)

    Glud, A. N.; Bech, J.; Tvilling, L.

    and subcortical anatomical differences. NEW METHOD: We present a convenient method to make an MRI-visible skull fiducial for 3D MRI-based stereotaxic procedures in larger experimental animals. Plastic screws were filled with either copper-sulphate solution or MRI-visible paste from a commercially available......BACKGROUND: Stereotaxic neurosurgery in large animals is used widely in different sophisticated models, where precision is becoming more crucial as desired anatomical target regions are becoming smaller. Individually calculated coordinates are necessary in large animal models with cortical...... cranial head marker. The screw fiducials were inserted in the animal skulls and T1 weighted MRI was performed allowing identification of the inserted skull marker. RESULTS: Both types of fiducial markers were clearly visible on the MRÍs. This allows high precision in the stereotaxic space. COMPARISON...

  5. Lateral dynamic flight stability of a model hoverfly in normal and inclined stroke-plane hovering

    International Nuclear Information System (INIS)

    Xu, Na; Sun, Mao

    2014-01-01

    Many insects hover with their wings beating in a horizontal plane (‘normal hovering’), while some insects, e.g., hoverflies and dragonflies, hover with inclined stroke-planes. Here, we investigate the lateral dynamic flight stability of a hovering model hoverfly. The aerodynamic derivatives are computed using the method of computational fluid dynamics, and the equations of motion are solved by the techniques of eigenvalue and eigenvector analysis. The following is shown: The flight of the insect is unstable at normal hovering (stroke-plane angle equals 0) and the instability becomes weaker as the stroke-plane angle increases; the flight becomes stable at a relatively large stroke-plane angle (larger than about 24°). As previously shown, the instability at normal hovering is due to a positive roll-moment/side-velocity derivative produced by the ‘changing-LEV-axial-velocity’ effect. When the stroke-plane angle increases, the wings bend toward the back of the body, and the ‘changing-LEV-axial-velocity’ effect decreases; in addition, another effect, called the ‘changing-relative-velocity’ effect (the ‘lateral wind’, which is due to the side motion of the insect, changes the relative velocity of its wings), becomes increasingly stronger. This causes the roll-moment/side-velocity derivative to first decrease and then become negative, resulting in the above change in stability as a function of the stroke-plane angle. (paper)

  6. Procoagulant snake venoms have differential effects in animal plasmas: Implications for antivenom testing in animal models.

    Science.gov (United States)

    Maduwage, Kalana P; Scorgie, Fiona E; Lincz, Lisa F; O'Leary, Margaret A; Isbister, Geoffrey K

    2016-01-01

    Animal models are used to test toxic effects of snake venoms/toxins and the antivenom required to neutralise them. However, venoms that cause clinically relevant coagulopathy in humans may have differential effects in animals. We aimed to investigate the effect of different procoagulant snake venoms on various animal plasmas. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were measured in seven animal plasmas (human, rabbit, cat, guinea pig, pig, cow and rat). In vitro clotting times were then used to calculate the effective concentration (EC50) in each plasma for four snake venoms with different procoagulant toxins: Pseudonaja textilis, Daboia russelli, Echis carinatus and Calloselasma rhodostoma. Compared to human, PT and aPTT were similar for rat, rabbit and pig, but double for cat and cow, while guinea pig had similar aPTT but double PT. Fibrinogen and D-dimer levels were similar for all species. Human and rabbit plasmas had the lowest EC50 for P. textilis (0.1 and 0.4 μg/ml), D. russelli (0.4 and 0.1 μg/ml), E. carinatus (0.6 and 0.1 μg/ml) venoms respectively, while cat plasma had the lowest EC50 for C. rhodostoma (11 μg/ml) venom. Cow, rat, pig and guinea pig plasmas were highly resistant to all four venoms with EC50 10-fold that of human. Different animal plasmas have varying susceptibility to procoagulant venoms, and excepting rabbits, animal models are not appropriate to test procoagulant activity. In vitro assays on human plasma should instead be adopted for this purpose. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Advancing research on animal-transported subsidies by integrating animal movement and ecosystem modelling.

    Science.gov (United States)

    Earl, Julia E; Zollner, Patrick A

    2017-09-01

    Connections between ecosystems via animals (active subsidies) support ecosystem services and contribute to numerous ecological effects. Thus, the ability to predict the spatial distribution of active subsidies would be useful for ecology and conservation. Previous work modelling active subsidies focused on implicit space or static distributions, which treat passive and active subsidies similarly. Active subsidies are fundamentally different from passive subsidies, because animals can respond to the process of subsidy deposition and ecosystem changes caused by subsidy deposition. We propose addressing this disparity by integrating animal movement and ecosystem ecology to advance active subsidy investigations, make more accurate predictions of subsidy spatial distributions, and enable a mechanistic understanding of subsidy spatial distributions. We review selected quantitative techniques that could be used to accomplish integration and lead to novel insights. The ultimate objective for these types of studies is predictions of subsidy spatial distributions from characteristics of the subsidy and the movement strategy employed by animals that transport subsidies. These advances will be critical in informing the management of ecosystem services, species conservation and ecosystem degradation related to active subsidies. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

  8. Research advances in animal models of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    HUANG Haiyan

    2014-09-01

    Full Text Available In recent years, the incidence of nonalcoholic fatty liver disease (NAFLD has increased gradually along with the rising prevalence of obesity, type 2 diabetes, and hyperlipidemia, and NAFLD has become one of the most common chronic liver diseases in the world and the second major liver disease after chronic viral hepatitis in China. However, its pathogenesis has not yet been clarified. Animal models are playing an important role in researches on NAFLD due to the facts that the development and progression of NAFLD require a long period of time, and ethical limitations exist in conducting drug trials in patients or collecting liver tissues from patients. The animal models with histopathology similar to that of NAFLD patients are reviewed, and their modeling principle, as well as the advantages and disadvantages, are compared. Animal models provide a powerful tool for further studies of NAFLD pathogenesis and drug screening for prevention and treatment of NAFLD.

  9. Animal models for the study of Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Eliza Miszczyk

    2014-05-01

    Full Text Available The Gram-negative bacillus Helicobacter pylori is widely recognized as a major etiologic agent responsible for chronic active gastritis, peptic ulcers, the development of gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma. Still, little is known about the natural history of H. pylori infection, since patients usually after many years of not suffering from symptoms of the infection are simply asymptomatic. Since the research investigators carried out on human models has many limitations, there is an urgent need for the development of an animal model optimal and suitable for the monitoring of H. pylori infections. This review summarizes the recent findings on the suitability of animal models used in H. pylori research. Several animal models are useful for the assessment of pathological, microbiological and immunological consequences of infection, which makes it possible to monitor the natural

  10. Th17 in Animal Models of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Motomu Hashimoto

    2017-07-01

    Full Text Available IL-17-secreting helper CD4 T cells (Th17 cells constitute a newly identified subset of helper CD4 T cells that play a key role in the development of rheumatoid arthritis (RA in its animal models. Recently, several models of spontaneous RA, which elucidate the mechanism of RA onset, have been discovered. These animal models shed new light on the role of Th17 in the development of autoimmune arthritis. Th17 cells coordinate inflammation and promote joint destruction, acting on various cells, including neutrophils, macrophages, synovial fibroblasts, and osteoclasts. Regulatory T cells cannot control Th17 cells under conditions of inflammation. In this review, the pathogenic role of Th17 cells in arthritis development, which was revealed by the recent animal models of RA, is discussed.

  11. Th17 in Animal Models of Rheumatoid Arthritis.

    Science.gov (United States)

    Hashimoto, Motomu

    2017-07-21

    IL-17-secreting helper CD4 T cells (Th17 cells) constitute a newly identified subset of helper CD4 T cells that play a key role in the development of rheumatoid arthritis (RA) in its animal models. Recently, several models of spontaneous RA, which elucidate the mechanism of RA onset, have been discovered. These animal models shed new light on the role of Th17 in the development of autoimmune arthritis. Th17 cells coordinate inflammation and promote joint destruction, acting on various cells, including neutrophils, macrophages, synovial fibroblasts, and osteoclasts. Regulatory T cells cannot control Th17 cells under conditions of inflammation. In this review, the pathogenic role of Th17 cells in arthritis development, which was revealed by the recent animal models of RA, is discussed.

  12. Animal Models for Tuberculosis in Translational and Precision Medicine

    Directory of Open Access Journals (Sweden)

    Lingjun Zhan

    2017-05-01

    Full Text Available Tuberculosis (TB is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models.

  13. ANIMAL MODELS OF POST-TRAUMATIC STRESS DISORDER: FACE VALIDITY

    Directory of Open Access Journals (Sweden)

    SONAL eGOSWAMI

    2013-05-01

    Full Text Available Post-traumatic stress disorder (PTSD is a debilitating condition that develops in a proportion of individuals following a traumatic event. Despite recent advances, ethical limitations associated with human research impede progress in understanding PTSD. Fortunately, much effort has focused on developing animal models to help study the pathophysiology of PTSD. Here, we provide an overview of animal PTSD models where a variety of stressors (physical, psychosocial, or psychogenic are used to examine the long-term effects of severe trauma. We emphasize models involving predator threat because they reproduce human individual differences in susceptibility to, and in the long-term consequences of, psychological trauma.

  14. Animal models of post-traumatic stress disorder: face validity

    Science.gov (United States)

    Goswami, Sonal; Rodríguez-Sierra, Olga; Cascardi, Michele; Paré, Denis

    2013-01-01

    Post-traumatic stress disorder (PTSD) is a debilitating condition that develops in a proportion of individuals following a traumatic event. Despite recent advances, ethical limitations associated with human research impede progress in understanding PTSD. Fortunately, much effort has focused on developing animal models to help study the pathophysiology of PTSD. Here, we provide an overview of animal PTSD models where a variety of stressors (physical, psychosocial, or psychogenic) are used to examine the long-term effects of severe trauma. We emphasize models involving predator threat because they reproduce human individual differences in susceptibility to, and in the long-term consequences of, psychological trauma. PMID:23754973

  15. Animal Models for Tuberculosis in Translational and Precision Medicine.

    Science.gov (United States)

    Zhan, Lingjun; Tang, Jun; Sun, Mengmeng; Qin, Chuan

    2017-01-01

    Tuberculosis (TB) is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models.

  16. Animal Models for the Study of Female Sexual Dysfunction

    Science.gov (United States)

    Marson, Lesley; Giamberardino, Maria Adele; Costantini, Raffaele; Czakanski, Peter; Wesselmann, Ursula

    2017-01-01

    Introduction Significant progress has been made in elucidating the physiological and pharmacological mechanisms of female sexual function through preclinical animal research. The continued development of animal models is vital for the understanding and treatment of the many diverse disorders that occur in women. Aim To provide an updated review of the experimental models evaluating female sexual function that may be useful for clinical translation. Methods Review of English written, peer-reviewed literature, primarily from 2000 to 2012, that described studies on female sexual behavior related to motivation, arousal, physiological monitoring of genital function and urogenital pain. Main Outcomes Measures Analysis of supporting evidence for the suitability of the animal model to provide measurable indices related to desire, arousal, reward, orgasm, and pelvic pain. Results The development of female animal models has provided important insights in the peripheral and central processes regulating sexual function. Behavioral models of sexual desire, motivation, and reward are well developed. Central arousal and orgasmic responses are less well understood, compared with the physiological changes associated with genital arousal. Models of nociception are useful for replicating symptoms and identifying the neurobiological pathways involved. While in some cases translation to women correlates with the findings in animals, the requirement of circulating hormones for sexual receptivity in rodents and the multifactorial nature of women’s sexual function requires better designed studies and careful analysis. The current models have studied sexual dysfunction or pelvic pain in isolation; combining these aspects would help to elucidate interactions of the pathophysiology of pain and sexual dysfunction. Conclusions Basic research in animals has been vital for understanding the anatomy, neurobiology, and physiological mechanisms underlying sexual function and urogenital pain

  17. Food allergy: What do we learn from animal models?

    NARCIS (Netherlands)

    Knippels, L.M.J.; Wijk, F. van; Penninks, A.H.

    2004-01-01

    Purpose of review This review summarizes selected articles on animal models of food allergy published in 2003. The research areas that are covered include mechanistic studies, the search for new therapies, as well as screening models for hazard identification of potential allergens. Recent findings

  18. Animal models for human genetic diseases | Sharif | African Journal ...

    African Journals Online (AJOL)

    The study of human genetic diseases can be greatly aided by animal models because of their similarity to humans in terms of genetics. In addition to understand diverse aspects of basic biology, model organisms are extensively used in applied research in agriculture, industry, and also in medicine, where they are used to ...

  19. An animal model to train Lichtenstein inguinal hernia repair

    DEFF Research Database (Denmark)

    Rosenberg, J; Presch, I; Pommergaard, H C

    2013-01-01

    pigs, and a total of 55 surgeons have been educated to perform Lichtenstein's hernia repair in these animals. CONCLUSIONS: This new experimental surgical model for training Lichtenstein's hernia repair mimics the human inguinal anatomy enough to make it suitable as a training model. The operation...

  20. Obsessive-compulsive disorder: Insights from animal models.

    Science.gov (United States)

    Szechtman, Henry; Ahmari, Susanne E; Beninger, Richard J; Eilam, David; Harvey, Brian H; Edemann-Callesen, Henriette; Winter, Christine

    2017-05-01

    Research with animal models of obsessive-compulsive disorder (OCD) shows the following: (1) Optogenetic studies in mice provide evidence for a plausible cause-effect relation between increased activity in cortico-basal ganglia-thalamo-cortical (CBGTC) circuits and OCD by demonstrating the induction of compulsive behavior with the experimental manipulation of the CBGTC circuit. (2) Parallel use of several animal models is a fruitful paradigm to examine the mechanisms of treatment effects of deep brain stimulation in distinct OCD endophenotypes. (3) Features of spontaneous behavior in deer mice constitute a rich platform to investigate the neurobiology of OCD, social ramifications of a compulsive phenotype, and test novel drugs. (4) Studies in animal models for psychiatric disorders comorbid with OCD suggest comorbidity may involve shared neural circuits controlling expression of compulsive behavior. (5) Analysis of compulsive behavior into its constitutive components provides evidence from an animal model for a motivational perspective on OCD. (6) Methods of behavioral analysis in an animal model translate to dissection of compulsive rituals in OCD patients, leading to diagnostic tests. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Chest compressions in newborn animal models: A review.

    Science.gov (United States)

    Solevåg, Anne Lee; Cheung, Po-Yin; Lie, Helene; O'Reilly, Megan; Aziz, Khalid; Nakstad, Britt; Schmölzer, Georg Marcus

    2015-11-01

    Much of the knowledge about the optimal way to perform chest compressions (CC) in newborn infants is derived from animal studies. The objective of this review was to identify studies of CC in newborn term animal models and review the evidence. We also provide an overview of the different models. MEDLINE, EMBASE and CINAHL, until September 29th 2014. Study eligibility criteria and interventions: term newborn animal models where CC was performed. Based on 419 retrieved studies from MEDLINE and 502 from EMBASE, 28 studies were included. No additional studies were identified in CINAHL. Most of the studies were performed in pigs after perinatal transition without long-term follow-up. The models differed widely in methodological aspects, which limits the possibility to compare and synthesize findings. Studies uncommonly reported the method for randomization and allocation concealment, and a limited number were blinded. Only the evidence in favour of the two-thumb encircling hands technique for performing CC, a CC to ventilation ratio of 3:1; and that air can be used for ventilation during CC; was supported by more than one study. Animal studies should be performed and reported with the same rigor as in human randomized trials. Good transitional and survival models are needed to further increase the strength of the evidence derived from animal studies of newborn chest compressions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. How animal models inform child and adolescent psychiatry.

    Science.gov (United States)

    Stevens, Hanna E; Vaccarino, Flora M

    2015-05-01

    Every available approach should be used to advance the field of child and adolescent psychiatry. Biological systems are important for the behavioral problems of children. Close examination of nonhuman animals and the biology and behavior that they share with humans is an approach that must be used to advance the clinical work of child psychiatry. We review here how model systems are used to contribute to significant insights into childhood psychiatric disorders. Model systems have not only demonstrated causality of risk factors for psychiatric pathophysiology, but have also allowed child psychiatrists to think in different ways about risks for psychiatric disorders and multiple levels that might be the basis of recovery and prevention. We present examples of how animal systems are used to benefit child psychiatry, including through environmental, genetic, and acute biological manipulations. Animal model work has been essential in our current thinking about childhood disorders, including the importance of dose and timing of risk factors, specific features of risk factors that are significant, neurochemistry involved in brain functioning, molecular components of brain development, and the importance of cellular processes previously neglected in psychiatric theories. Animal models have clear advantages and disadvantages that must be considered for these systems to be useful. Coupled with increasingly sophisticated methods for investigating human behavior and biology, animal model systems will continue to make essential contributions to our field. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Animal models of GM2 gangliosidosis: utility and limitations

    Directory of Open Access Journals (Sweden)

    Lawson CA

    2016-07-01

    Full Text Available Cheryl A Lawson,1,2 Douglas R Martin2,3 1Department of Pathobiology, 2Scott-Ritchey Research Center, 3Department of Anatomy, Physiology and Pharmacology, Auburn University College of Veterinary Medicine, Auburn, AL, USA Abstract: GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. Keywords: GM2 gangliosidosis, Tay–Sachs disease, Sandhoff disease, lysosomal storage disorder, sphingolipidosis, brain disease

  4. Animal models of GM2 gangliosidosis: utility and limitations.

    Science.gov (United States)

    Lawson, Cheryl A; Martin, Douglas R

    2016-01-01

    GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay-Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay-Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described.

  5. Queue-based modelling and detection of parameters involved in stroke outcome

    DEFF Research Database (Denmark)

    Vilic, Adnan; Petersen, John Asger; Wienecke, Troels

    2017-01-01

    We designed a queue-based model, and investigated which parameters are of importance when predicting stroke outcome. Medical record forms have been collected for 57 ischemic stroke patients, including medical history and vital sign measurement along with neurological scores for the first twenty-f......, where outcome for patients were 36.75 ± 10.99. The queue-based model integrating multiple linear regression shows promising results for automatic selection of significant medically relevant parameters.......-four hours of admission. The importance of each parameter is identified using multiple regression combined with a circular queue to iteratively fit outcome. Out of 39 parameters, the model isolated 14 which combined could estimate outcome with a root mean square error of 1.69 on the Scandinavian Stroke Scale...

  6. The use of animal models in behavioural neuroscience research.

    Science.gov (United States)

    Bovenkerk, Bernice; Kaldewaij, Frederike

    2015-01-01

    Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are also likely to be considered the ones that are most morally problematic to use, if it seems probable that (and if indeed they are initially selected as models because) they have experiences that are similar to human experiences that we have strong reasons to avoid causing, and indeed aim to alleviate (such as pain, anxiety or sadness). In this paper, against the background of contemporary discussions in animal ethics and the philosophy of animal minds, we discuss the views that it is morally permissible to use animals in these kinds of experiments, and that it is better to use less cognitively complex animals (such as zebrafish) than more complex animals (such as dogs). First, we criticise some justifications for the claim that human beings and more complex animals have higher moral status. We argue that contemporary approaches that attribute equal moral status to all beings that are capable of conscious strivings strivings (e.g. avoiding pain and anxiety; aiming to eat and play) are based on more plausible assumptions. Second, we argue that it is problematic to assume that less cognitively complex animals have a lesser sensory and emotional experience than more complex beings across the board. In specific cases, there might be good reasons to assume that more complex beings would be harmed more by a specific physical or environmental intervention, but it might also be that they sometimes are harmed less because of a better ability to cope. Determining whether a specific experiment is justified is therefore a complex issue. Our aim in this chapter is to stimulate further reflection on these common assumptions behind the use of animal models for psychopathologies. In

  7. Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

    Science.gov (United States)

    Hu, Heng; Doll, Danielle N.; Sun, Jiahong; Lewis, Sara E.; Wimsatt, Jeffrey H.; Kessler, Matthew J.; Simpkins, James W.; Ren, Xuefang

    2016-01-01

    Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for

  8. Amphibians as animal models for laboratory research in physiology.

    Science.gov (United States)

    Burggren, Warren W; Warburton, Stephen

    2007-01-01

    The concept of animal models is well honored, and amphibians have played a prominent part in the success of using key species to discover new information about all animals. As animal models, amphibians offer several advantages that include a well-understood basic physiology, a taxonomic diversity well suited to comparative studies, tolerance to temperature and oxygen variation, and a greater similarity to humans than many other currently popular animal models. Amphibians now account for approximately 1/4 to 1/3 of lower vertebrate and invertebrate research, and this proportion is especially true in physiological research, as evident from the high profile of amphibians as animal models in Nobel Prize research. Currently, amphibians play prominent roles in research in the physiology of musculoskeletal, cardiovascular, renal, respiratory, reproductive, and sensory systems. Amphibians are also used extensively in physiological studies aimed at generating new insights in evolutionary biology, especially in the investigation of the evolution of air breathing and terrestriality. Environmental physiology also utilizes amphibians, ranging from studies of cryoprotectants for tissue preservation to physiological reactions to hypergravity and space exploration. Amphibians are also playing a key role in studies of environmental endocrine disruptors that are having disproportionately large effects on amphibian populations and where specific species can serve as sentinel species for environmental pollution. Finally, amphibian genera such as Xenopus, a genus relatively well understood metabolically and physiologically, will continue to contribute increasingly in this new era of systems biology and "X-omics."

  9. Engineering Large Animal Species to Model Human Diseases.

    Science.gov (United States)

    Rogers, Christopher S

    2016-07-01

    Animal models are an important resource for studying human diseases. Genetically engineered mice are the most commonly used species and have made significant contributions to our understanding of basic biology, disease mechanisms, and drug development. However, they often fail to recreate important aspects of human diseases and thus can have limited utility as translational research tools. Developing disease models in species more similar to humans may provide a better setting in which to study disease pathogenesis and test new treatments. This unit provides an overview of the history of genetically engineered large animals and the techniques that have made their development possible. Factors to consider when planning a large animal model, including choice of species, type of modification and methodology, characterization, production methods, and regulatory compliance, are also covered. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  10. Alternative animal model for studies of total skin thickness burns.

    Science.gov (United States)

    Andrade, Ana Laura Martins de; Parisi, Julia Risso; Brassolatti, Patrícia; Parizotto, Nivaldo Antonio

    2017-10-01

    To present an alternative experimental model of third degree burn of easy reproducibility. Eighteen male Wister rats were randomly divided into three groups, 6 of which were allocated to each group. A soldering iron coupled to an aluminum plate was used to produce burn, at a temperature of 150ºC, with different exposure times per group. Group 5 (G5) animals were burned at 150°C with exposure time of 5 seconds; Group 10 (G10) the animals were burned at 150°C with exposure time of 10 seconds and group 15 (G15) the animals were burned at 150°C with exposure time of 15 seconds. Histopathological analyzes showed that all three groups had similar morphological characteristics, with total thickness involvement. The technique is effective to reproduce a third degree burn and suggests the temperature of 150ºC with 5 seconds of exposure in order to minimize the risks to the animals.

  11. Animal Models of Diabetic Retinopathy: Summary and Comparison

    Science.gov (United States)

    Lo, Amy C. Y.

    2013-01-01

    Diabetic retinopathy (DR) is a microvascular complication associated with chronic exposure to hyperglycemia and is a major cause of blindness worldwide. Although clinical assessment and retinal autopsy of diabetic patients provide information on the features and progression of DR, its underlying pathophysiological mechanism cannot be deduced. In order to have a better understanding of the development of DR at the molecular and cellular levels, a variety of animal models have been developed. They include pharmacological induction of hyperglycemia and spontaneous diabetic rodents as well as models of angiogenesis without diabetes (to compensate for the absence of proliferative DR symptoms). In this review, we summarize the existing protocols to induce diabetes using STZ. We also describe and compare the pathological presentations, in both morphological and functional aspects, of the currently available DR animal models. The advantages and disadvantages of using different animals, ranging from zebrafish, rodents to other higher-order mammals, are also discussed. Until now, there is no single model that displays all the clinical features of DR as seen in human. Yet, with the understanding of the pathological findings in these animal models, researchers can select the most suitable models for mechanistic studies or drug screening. PMID:24286086

  12. Animal models of disc degeneration and major genetic strategies.

    Science.gov (United States)

    Sun, Fu; Qu, Ji-Ning; Zhang, Yin-Gang

    2013-01-01

    The establishment of a reliable animal model of lumbar disc degeneration (AMDD) is important for studying pathogenesis and evaluating treatment effectiveness. However, an ideal AMDD for use in laboratory studies has not yet been produced. This retrospective study reviews and compares several common AMDD and discusses their strengths and weaknesses. We also suggest a new method for establishing future AMDD. The identified genes associated with disc degeneration are susceptibility genes, which elevate risk but do not necessarily lead to disease occurrence. We propose to identify families with hereditary disc degeneration, find major casual genes with exome sequencing, and establish transgenic animal models. This approach may help us to build an improved AMDD.

  13. Simple models for studying complex spatiotemporal patterns of animal behavior

    Science.gov (United States)

    Tyutyunov, Yuri V.; Titova, Lyudmila I.

    2017-06-01

    Minimal mathematical models able to explain complex patterns of animal behavior are essential parts of simulation systems describing large-scale spatiotemporal dynamics of trophic communities, particularly those with wide-ranging species, such as occur in pelagic environments. We present results obtained with three different modelling approaches: (i) an individual-based model of animal spatial behavior; (ii) a continuous taxis-diffusion-reaction system of partial-difference equations; (iii) a 'hybrid' approach combining the individual-based algorithm of organism movements with explicit description of decay and diffusion of the movement stimuli. Though the models are based on extremely simple rules, they all allow description of spatial movements of animals in a predator-prey system within a closed habitat, reproducing some typical patterns of the pursuit-evasion behavior observed in natural populations. In all three models, at each spatial position the animal movements are determined by local conditions only, so the pattern of collective behavior emerges due to self-organization. The movement velocities of animals are proportional to the density gradients of specific cues emitted by individuals of the antagonistic species (pheromones, exometabolites or mechanical waves of the media, e.g., sound). These cues play a role of taxis stimuli: prey attract predators, while predators repel prey. Depending on the nature and the properties of the movement stimulus we propose using either a simplified individual-based model, a continuous taxis pursuit-evasion system, or a little more detailed 'hybrid' approach that combines simulation of the individual movements with the continuous model describing diffusion and decay of the stimuli in an explicit way. These can be used to improve movement models for many species, including large marine predators.

  14. The enduring importance of animal models in understanding periodontal disease.

    Science.gov (United States)

    Hajishengallis, George; Lamont, Richard J; Graves, Dana T

    2015-01-01

    Whereas no single animal model can reproduce the complexity of periodontitis, different aspects of the disease can be addressed by distinct models. Despite their limitations, animal models are essential for testing the biological significance of in vitro findings and for establishing cause-and-effect relationships relevant to clinical observations, which are typically correlative. We provide evidence that animal-based studies have generated a durable framework for dissecting the mechanistic basis of periodontitis. These studies have solidified the etiologic role of bacteria in initiating the inflammatory response that leads to periodontal bone loss and have identified key mediators (IL-1, TNF, prostaglandins, complement, RANKL) that induce inflammatory breakdown. Moreover, animal studies suggest that dysbiosis, rather than individual bacterial species, are important in initiating periodontal bone loss and have introduced the concept that organisms previously considered commensals can play important roles as accessory pathogens or pathobionts. These studies have also provided insight as to how systemic conditions, such as diabetes or leukocyte adhesion deficiency, contribute to tissue destruction. In addition, animal studies have identified and been useful in testing therapeutic targets.

  15. Cardiovascular Imaging: What Have We Learned From Animal Models?

    Directory of Open Access Journals (Sweden)

    Arnoldo eSantos

    2015-10-01

    Full Text Available Cardiovascular imaging has become an indispensable tool for patient diagnosis and follow up. Probably the wide clinical applications of imaging are due to the possibility of a detailed and high quality description and quantification of cardiovascular system structure and function. Also phenomena that involve complex physiological mechanisms and biochemical pathways, such as inflammation and ischemia, can be visualized in a nondestructive way. The widespread use and evolution of imaging would not have been possible without animal studies. Animal models have allowed for instance, i the technical development of different imaging tools, ii to test hypothesis generated from human studies and finally, iii to evaluate the translational relevance assessment of in vitro and ex-vivo results. In this review, we will critically describe the contribution of animal models to the use of biomedical imaging in cardiovascular medicine. We will discuss the characteristics of the most frequent models used in/for imaging studies. We will cover the major findings of animal studies focused in the cardiovascular use of the repeatedly used imaging techniques in clinical practice and experimental studies. We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases. In these diseases, imaging research using animals has allowed the study of aspects such as: ventricular size, shape, global function and wall thickening, local myocardial function, myocardial perfusion, metabolism and energetic assessment, infarct quantification, vascular lesion characterization, myocardial fiber structure, and myocardial calcium uptake. Finally we will discuss the limitations and future of imaging research with animal models.

  16. Contemporary Animal Models For Human Gene Therapy Applications.

    Science.gov (United States)

    Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Nelson, Everette Jacob Remington

    2015-01-01

    Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.

  17. Animal models for implant biomaterial research in bone: A review

    Directory of Open Access Journals (Sweden)

    A I Pearce

    2007-03-01

    Full Text Available Development of an optimal interface between bone and orthopaedic and dental implants has taken place for many years. In order to determine whether a newly developed implant material conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation. For this reason the use of animal models is often an essential step in the testing of orthopaedic and dental implants prior to clinical use in humans. This review discusses some of the more commonly available and frequently used animal models such as the dog, sheep, goat, pig and rabbit models for the evaluation of bone-implant interactions. Factors for consideration when choosing an animal model and implant design are discussed. Various bone specific features are discussed including the usage of the species, bone macrostructure and microstructure and bone composition and remodelling, with emphasis being placed on the similarity between the animal model and the human clinical situation. While the rabbit was the most commonly used of the species discussed in this review, it is clear that this species showed the least similarities to human bone. There were only minor differences in bone composition between the various species and humans. The pig demonstrated a good likeness with human bone however difficulties may be encountered in relation to their size and ease of handling. In this respect the dog and sheep/goat show more promise as animal models for the testing of bone implant materials. While no species fulfils all of the requirements of an ideal model, an understanding of the differences in bone architecture and remodelling between the species is likely to assist in the selection of a suitable species for a defined research question.

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

    Science.gov (United States)

    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.

  19. A systematic review of current osteoporotic metaphyseal fracture animal models.

    Science.gov (United States)

    Wong, R M Y; Choy, M H V; Li, M C M; Leung, K-S; K-H Chow, S; Cheung, W-H; Cheng, J C Y

    2018-01-01

    The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models. A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted. Fracture techniques included drill hole defects (3 of 19), bone defects (3 of 19), partial osteotomy (1 of 19), and complete osteotomies (12 of 19). Drill hole models and incomplete osteotomy models are easy to perform and allow the study of therapeutic agents but do not represent the usual clinical setting. Additionally, biomaterials can be filled into drill hole defects for analysis. Complete osteotomy models are most commonly used and are best suited for the investigation of therapeutic drugs or noninvasive interventions. The metaphyseal defect models allow the study of biomaterials, which are associated with complex and comminuted osteoporotic fractures. For a clinically relevant model, we propose that an animal model should satisfy the following criteria to study osteoporotic fracture healing: 1) induction of osteoporosis, 2) complete osteotomy or defect at the metaphysis unilaterally, and 3) internal fixation. Cite this article : R. M. Y. Wong, M. H. V. Choy, M. C. M. Li, K-S. Leung, S. K-H. Chow, W-H. Cheung, J. C. Y. Cheng. A systematic review of current osteoporotic metaphyseal fracture animal models. Bone Joint Res 2018;7:6-11. DOI: 10.1302/2046-3758.71.BJR-2016-0334.R2. © 2018 Wong et al.

  20. Overview on available animal models for application in leukemia research

    International Nuclear Information System (INIS)

    Borkhardt, A.; Sanchez-Garcia, I.; Cobaleda, C.; Hauer, J.

    2015-01-01

    The term ''leukemia'' encompasses a group of diseases with a variable clinical and pathological presentation. Its cellular origin, its biology and the underlying molecular genetic alterations determine the very variable and individual disease phenotype. The focus of this review is to discuss the most important guidelines to be taken into account when we aim at developing an ''ideal'' animal model to study leukemia. The animal model should mimic all the clinical, histological and molecular genetic characteristics of the human phenotype and should be applicable as a clinically predictive model. It should achieve all the requirements to be used as a standardized model adaptive to basic research as well as to pharmaceutical practice. Furthermore it should fulfill all the criteria to investigate environmental risk factors, the role of genomic mutations and be applicable for therapeutic testing. These constraints limit the usefulness of some existing animal models, which are however very valuable for basic research. Hence in this review we will primarily focus on genetically engineered mouse models (GEMMs) to study the most frequent types of childhood leukemia. GEMMs are robust models with relatively low site specific variability and which can, with the help of the latest gene modulating tools be adapted to individual clinical and research questions. Moreover they offer the possibility to restrict oncogene expression to a defined target population and regulate its expression level as well as its timely activity. Until recently it was only possible in individual cases to develop a murin model, which fulfills the above mentioned requirements. Hence the development of new regulatory elements to control targeted oncogene expression should be priority. Tightly controlled and cell specific oncogene expression can then be combined with a knock-in approach and will depict a robust murine model, which enables almost physiologic oncogene

  1. Principles for developing animal models of military PTSD

    Directory of Open Access Journals (Sweden)

    Nikolaos P. Daskalakis

    2014-08-01

    Full Text Available The extent to which animal studies can be relevant to military posttraumatic stress disorder (PTSD continues to be a matter of discussion. Some features of the clinical syndrome are more easily modeled than others. In the animal literature, a great deal of attention is focused on modeling the characteristics of military exposures and their impact on measurable behaviors and biological parameters. There are many issues to consider regarding the ecological validity of predator, social defeat or immobilization stress to combat-related experience. In contrast, less attention has been paid to individual variation following these exposures. Such variation is critical to understand how individual differences in the response to military trauma exposure may result to PTSD or resilience. It is important to consider potential differences in biological findings when comparing extremely exposed to non-exposed animals, versus those that result from examining individual differences. Animal models of military PTSD are also critical in advancing efforts in clinical treatment. In an ideal translational approach to study deployment related outcomes, information from humans and animals, blood and brain, should be carefully considered in tandem, possibly even computed simultaneously, to identify molecules, pathways and networks that are likely to be the key drivers of military PTSD symptoms. With the use novel biological methodologies (e.g., optogenetics in the animal models, critical genes and pathways can be tuned up or down (rather than over-expressed or ablated completely in discrete brain regions. Such techniques together with pre-and post-deployment human imaging will accelerate the identification of novel pharmacological and non-pharmacological intervention strategies.

  2. Concise Review: Stem Cell Trials Using Companion Animal Disease Models.

    Science.gov (United States)

    Hoffman, Andrew M; Dow, Steven W

    2016-07-01

    Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729. © 2016 AlphaMed Press.

  3. Animal Models of Diabetes Mellitus for Islet Transplantation

    Directory of Open Access Journals (Sweden)

    Naoaki Sakata

    2012-01-01

    Full Text Available Due to current improvements in techniques for islet isolation and transplantation and protocols for immunosuppressants, islet transplantation has become an effective treatment for severe diabetes patients. Many diabetic animal models have contributed to such improvements. In this paper, we focus on 3 types of models with different mechanisms for inducing diabetes mellitus (DM: models induced by drugs including streptozotocin (STZ, pancreatomized models, and spontaneous models due to autoimmunity. STZ-induced diabetes is one of the most commonly used experimental diabetic models and is employed using many specimens including rodents, pigs or monkeys. The management of STZ models is well established for islet studies. Pancreatomized models reveal different aspects compared to STZ-induced models in terms of loss of function in the increase and decrease of blood glucose and therefore are useful for evaluating the condition in total pancreatomized patients. Spontaneous models are useful for preclinical studies including the assessment of immunosuppressants because such models involve the same mechanisms as type 1 DM in the clinical setting. In conclusion, islet researchers should select suitable diabetic animal models according to the aim of the study.

  4. Animation Augmented Reality Book Model (AAR Book Model) to Enhance Teamwork

    Science.gov (United States)

    Chujitarom, Wannaporn; Piriyasurawong, Pallop

    2017-01-01

    This study aims to synthesize an Animation Augmented Reality Book Model (AAR Book Model) to enhance teamwork and to assess the AAR Book Model to enhance teamwork. Samples are five specialists that consist of one animation specialist, two communication and information technology specialists, and two teaching model design specialists, selected by…

  5. Geospatial forecast model for tsetse-transmitted animal ...

    African Journals Online (AJOL)

    Results indicate that GIS model developed for parasitic diseases based on growing degree day (GDD) concept can be applied to tsetse-transmitted trypanosomosis. GIS for animal trypanosomosis was created using Food and Agriculture Organization – Crop Production System Zones (FAO-CPSZ) database and Normalized ...

  6. Unraveling the genetics of chronic kidney disease using animal models

    NARCIS (Netherlands)

    Korstanje, Ron; DiPetrillo, K.

    2004-01-01

    Identifying genes underlying common forms of kidney disease in humans has proven difficult, expensive, and time consuming. Quantitative trait loci (QTL) for several complex traits are concordant among mice, rats, and humans, suggesting that genetic findings from these animal models are relevant to

  7. In search for animal models of female sexual dysfunction

    NARCIS (Netherlands)

    Snoeren, E.M.S.

    2010-01-01

    Female Sexual Dysfunction (FSD) is a disorder that affects around 40% of the population. Low sexual arousal and low sexual desire are the most common problems. The mechanisms underlying the disorder are still unclear. The aims of this thesis were 1) the search for animal models of FSD, 2) the

  8. Animation Model to Conceptualize ATP Generation: A Mitochondrial Oxidative Phosphorylation

    Science.gov (United States)

    Jena, Ananta Kumar

    2015-01-01

    Adenosine triphosphate (ATP) is the molecular unit of intracellular energy and it is the product of oxidative phosphorylation of cellular respiration uses in cellular processes. The study explores the growth of the misconception levels amongst the learners and evaluates the effectiveness of animation model over traditional methods. The data…

  9. Animal models for plaque rupture: a biomechanical assessment

    NARCIS (Netherlands)

    van der Heiden, Kim; Hoogendoorn, Ayla; Daemen, Mat J.; Gijsen, Frank J. H.

    2016-01-01

    Rupture of atherosclerotic plaques is the main cause of acute cardiovascular events. Animal models of plaque rupture are rare but essential for testing new imaging modalities to enable diagnosis of the patient at risk. Moreover, they enable the design of new treatment strategies to prevent plaque

  10. The miniature pig as an animal model in biomedical research

    Czech Academy of Sciences Publication Activity Database

    Vodička, Petr; Smetana Jr., K.; Dvořánková, B.; Emerick, T.; Xu, Y.; Ourednik, J.; Ourednik, V.; Motlík, Jan

    2005-01-01

    Roč. 1049, - (2005), s. 161-171 ISSN 0077-8923 R&D Projects: GA MŠk(CZ) LN00A065 Institutional research plan: CEZ:AV0Z50450515 Keywords : animal model * stem cell * transgenic pig Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.971, year: 2005

  11. Genetic Evaluation and Ranking of Different Animal Models Using ...

    African Journals Online (AJOL)

    An animal model utilizes all relationships available in a given data set. Estimates for variance components for additive direct, additive maternal, maternal environmental and direct environmental effects, and their covariances between direct and maternal genetic effects for post weaning growth traits have been obtained with ...

  12. Modeling herbivorous animal digestive system as 3- continuous ...

    African Journals Online (AJOL)

    Modeling herbivorous animal digestive system as 3- continuous stirred tank reactor (CSTR) and 1-plug flow reactor (PFR) in series with specific reference to ... This shows the efficiency of each reactor at converting the purely lignocellulosics substrates to useful products like protein, vitamin, fatty acid and the bye-products.

  13. Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model

    NARCIS (Netherlands)

    Brouwer, E.; Huitema, M. G.; Klok, P. A.; de Weerd, H.; Tervaert, J. W.; Weening, J. J.; Kallenberg, C. G.

    1993-01-01

    To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO,

  14. ANTIMYELOPEROXIDASE-ASSOCIATED PROLIFERATIVE GLOMERULONEPHRITIS - AN ANIMAL-MODEL

    NARCIS (Netherlands)

    BROUWER, E; HUITEMA, MG; KLOK, PA; DEWEERD, H; TERVAERT, JWC; WEENING, JJ; KALLENBERG, CGM

    1993-01-01

    To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO,

  15. Animal models of human respiratory syncytial virus disease

    NARCIS (Netherlands)

    Bem, Reinout A.; Domachowske, Joseph B.; Rosenberg, Helene F.

    2011-01-01

    Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for

  16. A review of animal models for portal vein embolization

    NARCIS (Netherlands)

    Huisman, Floor; van Lienden, Krijn P.; Damude, Samantha; Hoekstra, Lisette T.; van Gulik, Thomas M.

    2014-01-01

    Portal vein embolization (PVE) is a preoperative intervention to increase the future remnant liver (FRL) through regeneration of the non-embolized liver lobes. This review assesses all the relevant animal models of PVE available, to guide researchers who intend to study PVE. We performed a

  17. Animal models for arthritis: innovative tools for prevention and treatment

    NARCIS (Netherlands)

    Kollias, G.; Papadaki, P.; Apparailly, F.; Vervoordeldonk, M.J.; Holmdahl, R.; Baumans, V.; Desaintes, C.; Di Santo, J.; Distler, J.; Garside, P.; Hegen, M.; Huizinga, T.W.J.; Jüngel, A.; Klareskog, L.; McInnes, I.; Ragoussis, I.; Schett, G.; Hart, B.t.; Tak, P.P.; Toes, R.; van den Berg, W.; Wurst, W.; Gay, S.

    2011-01-01

    The development of novel treatments for rheumatoid arthritis (RA) requires the interplay between clinical observations and studies in animal models. Given the complex molecular pathogenesis and highly heterogeneous clinical picture of RA, there is an urgent need to dissect its multifactorial nature

  18. Human neural stem cells over-expressing VEGF provide neuroprotection, angiogenesis and functional recovery in mouse stroke model.

    Directory of Open Access Journals (Sweden)

    Hong J Lee

    Full Text Available BACKGROUND: Intracerebral hemorrhage (ICH is a lethal stroke type. As mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs selectively migrate to the brain and induce behavioral recovery in rat ICH model, and that combined administration of NSCs and vascular endothelial growth factor (VEGF results in improved structural and functional outcome from cerebral ischemia. METHODS AND FINDINGS: We postulated that human NSCs overexpressing VEGF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs, increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by unilateral injection of bacterial collagenase into striatum. HB1.F3.VEGF human NSC line produced an amount of VEGF four times higher than parental F3 cell line in vitro, and induced behavioral improvement and 2-3 fold increase in cell survival at two weeks and eight weeks post-transplantation. CONCLUSIONS: Brain transplantation of F3 human NSCs over-expressing VEGF near ICH lesion sites provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results suggest a possible application of the human neural stem cell line, which is genetically modified to over-express VEGF, as a therapeutic agent for ICH-stroke.

  19. 75 FR 54349 - Animal Models-Essential Elements To Address Efficacy Under the Animal Rule; Notice of Public...

    Science.gov (United States)

    2010-09-07

    ... the Animal Rule; Notice of Public Meeting; and Reopening of Comment Period AGENCY: Food and Drug... challenges as addressed in the draft document entitled ``Guidance for ] Industry: Animal Models--Essential Elements to Address Efficacy Under the Animal Rule'' dated January 2009 (Draft Guidance), and as related to...

  20. Phenol-croton oil peel: establishing an animal model for scientific investigation.

    Science.gov (United States)

    Larson, David L; Karmo, Firas; Hetter, Greg P

    2009-01-01

    Phenol-croton oil formulas for facial peeling contain a mixture of phenol, croton oil, hexachlorophene foam (Septisol; Steris Corp., Mentor, OH), and water. For years, it was felt that the active ingredient of the solution was phenol, with the view that croton oil was little more than an irritant. Hetter reported, based on clinical experience, that the addition of tiny amounts of croton oil to any concentration of phenol caused a deeper peel. He also noted that the number of applications of a phenol-croton oil solution also enhanced the peel effects. To date, there have been no animal studies that confirm these clinical observations. The purpose of this study was to develop an animal model to further evaluate and refine the hypotheses of Hetter regarding the croton oil solution. At the Medical College of Wisconsin, Milwaukee, WI, using a porcine animal model, 40 different solutions of phenol, water, croton oil, hexachlorophene foam, and ethyl alcohol, in 8 groupings, were applied to the flank according to grids. On days 1, 8, and 22, clinical observations were made and punch biopsies were obtained from all grids, including controls. All tissue samples were examined by a blinded dermatopathologist. The results were analyzed by both clinical and histologic observation. Solutions with any amount of croton oil added had a brisker inflammatory response than solutions without croton oil. The histologic examination of skin biopsies from the phenol-treated cells (with or without croton oil) demonstrated formation of sharply demarcated dermis with parallel collagen fiber bundles arranged horizontally when compared with the elastotic dermis of the control specimens. The depth of peel and time needed for healing were greater with 45 strokes than with 20 or 5 strokes. Replacing water with ethyl alcohol produced a less clinically significant peel. Phenol peels more deeply with increasing concentrations. Peel depth increases with increasing concentration of croton oil. Multiple

  1. An Experimental Animal Model for Abdominal Fascia Healing after Surgery

    DEFF Research Database (Denmark)

    Burcharth, J; Pommergaard, H-C; Klein, M

    2013-01-01

    Background: Incisional hernia (IH) is a well-known complication after abdominal surgical procedures. The exact etiology of IH is still unknown even though many risk factors have been suggested. The aim of this study was to create an animal model of a weakly healed abdominal fascia that could...... be used to evaluate the actively healing fascia. Such an animal model may promote future research in the prevention of IH. Methods: 86 male Sprague-Dawley rats were used to establish a model involving six experiments (experiments A-F). Mechanical testing of the breaking strength of the healed fascia...... was performed by testing tissue strips from the healed fascia versus the unincised control fascia 7 and 28 days postoperatively. Results: During the six experiments a healing model was created that produced significantly weaker coherent fascia when compared with the control tissue measured in terms...

  2. Freshwater Planarians as an Alternative Animal Model for Neurotoxicology.

    Science.gov (United States)

    Hagstrom, Danielle; Cochet-Escartin, Olivier; Zhang, Siqi; Khuu, Cindy; Collins, Eva-Maria S

    2015-09-01

    Traditional toxicology testing has relied on low-throughput, expensive mammalian studies; however, timely testing of the large number of environmental toxicants requires new in vitro and in vivo platforms for inexpensive medium- to high-throughput screening. Herein, we describe the suitability of the asexual freshwater planarian Dugesia japonica as a new animal model for the study of developmental neurotoxicology. As these asexual animals reproduce by binary fission, followed by regeneration of missing body structures within approximately 1 week, development and regeneration occur through similar processes allowing us to induce neurodevelopment "at will" through amputation. This short time scale and the comparable sizes of full and regenerating animals enable parallel experiments in adults and developing worms to determine development-specific aspects of toxicity. Because the planarian brain, despite its simplicity, is structurally and molecularly similar to the mammalian brain, we are able to ascertain neurodevelopmental toxicity that is relevant to humans. As a proof of concept, we developed a 5-step semiautomatic screening platform to characterize the toxicity of 9 known neurotoxicants (consisting of common solvents, pesticides, and detergents) and a neutral agent, glucose, and quantified effects on viability, stimulated and unstimulated behavior, regeneration, and brain structure. Comparisons of our findings with other alternative toxicology animal models, such as zebrafish larvae and nematodes, demonstrated that planarians are comparably sensitive to the tested chemicals. In addition, we found that certain compounds induced adverse effects specifically in developing animals. We thus conclude that planarians offer new complementary opportunities for developmental neurotoxicology animal models. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. An animal model of spontaneous metabolic syndrome: Nile grass rat

    OpenAIRE

    Noda, Kousuke; Melhorn, Mark I.; Zandi, Souska; Frimmel, Sonja; Tayyari, Faryan; Hisatomi, Toshio; Almulki, Lama; Pronczuk, Andrzej; Hayes, K. C.; Hafezi-Moghadam, Ali

    2010-01-01

    Metabolic syndrome (MetS) is a prevalent and complex disease, characterized by the variable coexistence of obesity, dyslipidemia, hyperinsulinaemia, and hypertension. The alarming rise in the prevalence of metabolic disorders makes it imperative to innovate preventive or therapeutic measures for MetS and its complications. However, the elucidation of the pathogenesis of MetS has been hampered by the lack of realistic models. For example, the existing animal models of MetS, i.e., genetically e...

  4. Family Adaptation to Stroke: A Metasynthesis of Qualitative Research based on Double ABCX Model

    Directory of Open Access Journals (Sweden)

    Ali Hesamzadeh, RN, PhD Student of Nursing

    2015-09-01

    Conclusions: The results of the study are in conformity with the tenets of the Double ABCX Model. Family adaptation is a dynamic process and the present study findings provide rich information on proper assessment and intervention to the practitioners working with families of stroke survivors.

  5. 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.

  6. Experimental animal model for late postradiation reaction of the colon

    International Nuclear Information System (INIS)

    Trott, K.R.

    1987-01-01

    Experimental animal model worked out in Muenchen is discussed in which late postradiation reaction in Wistar rats following local irradiation of the colon manifests itself by appearance of colonic stenoses causing death of the animal. Clinical symptoms of this reaction together with results of histopathologic examination of the excised parts of the colon localized in the irradiated area are discussed. The relationships effect-dose obtained in this system for X radiation applying different regimen of dose fractionation and different total times of irradiation are presented. 8 refs., 5 figs., 1 tab. (author)

  7. Alternative animal model for studies of total skin thickness burns

    OpenAIRE

    Andrade, Ana Laura Martins de; Parisi, Julia Risso; Brassolatti, Patrícia; Parizotto, Nivaldo Antonio

    2017-01-01

    Abstract Purpose: To present an alternative experimental model of third degree burn of easy reproducibility. Methods: Eighteen male Wister rats were randomly divided into three groups, 6 of which were allocated to each group. A soldering iron coupled to an aluminum plate was used to produce burn, at a temperature of 150ºC, with different exposure times per group. Group 5 (G5) animals were burned at 150°C with exposure time of 5 seconds; Group 10 (G10) the animals were burned at 150°C with e...

  8. Peripheral biomarkers in animal models of major depressive disorder.

    Science.gov (United States)

    Carboni, Lucia

    2013-01-01

    Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with MDD are frequently measured. In contrast, other investigators evaluate peripheral analytes in preclinical models to translate the results in clinical settings afterwards. Large-scale, hypothesis-free studies are performed in MDD models to identify candidate biomarkers. Other studies wish to propose new targets for drug discovery. Animal models endowed with predictive validity are investigated, and the assessment of peripheral analytes, such as stress hormones or immune molecules, is comprised to increase the confidence in the target. Finally, since the mechanism of action of antidepressants is incompletely understood, studies investigating molecular alterations associated with antidepressant treatment may include peripheral analyte levels. In conclusion, preclinical biomarker studies aid the identification of new candidate analytes to be tested in clinical trials. They also increase our understanding of MDD pathophysiology and help to identify new pharmacological targets.

  9. Malarial birds: modeling infectious human disease in animals.

    Science.gov (United States)

    Slater, Leo B

    2005-01-01

    Through the examination of avian malarias as models of infectious human disease, this paper reveals the kinds of claims that scientists and physicians made on the basis of animal models-biological systems in the laboratory and the field-and what characteristics made for congruence between these models and human malaria. The focus is on the period between 1895 and 1945, and on the genesis and trajectory of certain animal models of malaria within specific locations, such as the Johns Hopkins School of Hygiene and Public Health in Baltimore and Bayer (I. G. Farben) in Elberfeld. These exemplars illustrate a diversity of approaches to malaria-as-disease, and the difficulties of framing aspects of this disease complex within an animal or laboratory system. The diversity and nearness to wild types of the birds, protozoan parasites, and mosquitoes that made up these malaria models contributed a great deal to the complexity of the models. Avian malarias, adopted with enthusiasm, were essential to the success of the U.S. antimalarial program during World War II.

  10. A Model for Predicting Persistent Elevation of Factor VIII among Patients with Acute Ischemic Stroke

    Science.gov (United States)

    Samai, Alyana A.; Boehme, Amelia K.; Shaban, Amir; George, Alexander J.; Dowell, Lauren; Monlezun, Dominique J.; Leissinger, Cindy; Schluter, Laurie; El Khoury, Ramy; Martin-Schild, Sheryl

    2016-01-01

    Background and Purpose Elevated levels of coagulation factor VIII (FVIII) may persist independent of the acute-phase response; however, this relationship has not been investigated relative to acute ischemic stroke (AIS). We examined the frequency and predictors of persistently elevated FVIII in AIS patients. Methods AIS patients admitted between July 2008 and May 2014 with elevated baseline FVIII levels and repeat FVIII levels drawn for more than 7 days postdischarge were included. The patients were dichotomized by repeat FVIII level for univariate analysis at 150% and 200% activity thresholds. An adjusted model was developed to predict the likelihood of persistently elevated FVIII levels. Results Among 1616 AIS cases, 98 patients with elevated baseline FVIII had repeat FVIII levels. Persistent FVIII elevation was found in more than 75% of patients. At the 150% threshold, the prediction score ranged from 0 to 7 and included black race, female sex, prior stroke, hyperlipidemia, smoking, baseline FVIII > 200%, and baseline von Willebrand factor (vWF) level greater than 200%. At the 200% threshold, the prediction score ranged from 0–5 and included female sex, prior stroke, diabetes mellitus, baseline FVIII level greater 200%, and baseline vWF level greater than 200%. For each 1-point increase in score, the odds of persistent FVIII at both the 150% threshold (odds ratio [OR] = 10.4, 95% confidence interval [CI] 1.63–66.9, P = .0134) and 200% threshold (OR = 10.2, 95% CI 1.82–57.5, P = .0083) increased 10 times. Conclusion Because an elevated FVIII level confers increased stroke risk, our model for anticipating a persistently elevated FVIII level may identify patients at high risk for recurrent stroke. FVIII may be a target for secondary stroke prevention. PMID:26777556

  11. Modelling animal waste pathogen transport from agricultural land to streams

    International Nuclear Information System (INIS)

    Pandey, Pramod K; Soupir, Michelle L; Ikenberry, Charles

    2014-01-01

    The transport of animal waste pathogens from crop land to streams can potentially elevate pathogen levels in stream water. Applying animal manure into crop land as fertilizers is a common practice in developing as well as in developed countries. Manure application into the crop land, however, can cause potential human health. To control pathogen levels in ambient water bodies such as streams, improving our understanding of pathogen transport at farm scale as well as at watershed scale is required. To understand the impacts of crop land receiving animal waste as fertilizers on stream's pathogen levels, here we investigate pathogen indicator transport at watershed scale. We exploited watershed scale hydrological model to estimate the transport of pathogens from the crop land to streams. Pathogen indicator levels (i.e., E. coli levels) in the stream water were predicted. With certain assumptions, model results are reasonable. This study can be used as guidelines for developing the models for calculating the impacts of crop land's animal manure on stream water

  12. Animal models of enterovirus 71 infection: applications and limitations

    Science.gov (United States)

    2014-01-01

    Human enterovirus 71 (EV71) has emerged as a neuroinvasive virus that is responsible for several outbreaks in the Asia-Pacific region over the past 15 years. Appropriate animal models are needed to understand EV71 neuropathogenesis better and to facilitate the development of effective vaccines and drugs. Non-human primate models have been used to characterize and evaluate the neurovirulence of EV71 after the early outbreaks in late 1990s. However, these models were not suitable for assessing the neurovirulence level of the virus and were associated with ethical and economic difficulties in terms of broad application. Several strategies have been applied to develop mouse models of EV71 infection, including strategies that employ virus adaption and immunodeficient hosts. Although these mouse models do not closely mimic human disease, they have been applied to determine the pathogenesis of and treatment and prevention of the disease. EV71 receptor-transgenic mouse models have recently been developed and have significantly advanced our understanding of the biological features of the virus and the host-parasite interactions. Overall, each of these models has advantages and disadvantages, and these models are differentially suited for studies of EV71 pathogenesis and/or the pre-clinical testing of antiviral drugs and vaccines. In this paper, we review the characteristics, applications and limitation of these EV71 animal models, including non-human primate and mouse models. PMID:24742252

  13. Animal models for Ebola and Marburg virus infections

    Science.gov (United States)

    Nakayama, Eri; Saijo, Masayuki

    2013-01-01

    Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

  14. Animal models for Ebola and Marburg virus infections

    Directory of Open Access Journals (Sweden)

    Eri eNakayama

    2013-09-01

    Full Text Available Ebola and Marburg hemorrhagic fevers (EHF and MHF are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus, respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4 pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using nonhuman primates (NHPs and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.

  15. An Animal Model Using Metallic Ions to Produce Autoimmune Nephritis

    Directory of Open Access Journals (Sweden)

    Roxana Ramírez-Sandoval

    2015-01-01

    Full Text Available Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO32. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis.

  16. Transmission of Helicobacter pyori in an animal model.

    Science.gov (United States)

    Cellini, L; Marzio, L; Ferrero, G; Del Vino, A; Di Campli, E; Grossi, L; Toracchio, S; Artese, L

    2001-01-01

    An experimental murine model was studied to evaluate the orogastrointestinal colonization of Helicobacter pylori and the animal-to-animal transmission. Balb/C mice were infected with H. pylori and housed with uninoculated mice in cages with and without a grate on the floor. Mice were killed after 7, 14, 30, and 45 days, and samples from the esophagus, stomach, small intestine, colon, and rectum were analyzed for H. pylori by PCR and immunohistochemistry and for histological changes. Bacterial colonization was assessed also by culture from stomach samples. H. pylori was cultured by stomach samples of infected mice at 7, 14, and 30 days. Using PCR and immunohistochemistry, H. pylori was detected in inoculated and uninoculated mice in all areas examined, with an high percentage of positive samples in the esophagus and stomach. Moreover transmission was detected, without differences, regardless of whether mice were housed with or without a grate on the floor, supporting an orooral animal transmission.

  17. Animal models of osteogenesis imperfecta: applications in clinical research

    Directory of Open Access Journals (Sweden)

    Enderli TA

    2016-09-01

    Full Text Available Tanya A Enderli, Stephanie R Burtch, Jara N Templet, Alessandra Carriero Department of Biomedical Engineering, Florida Institute of Technology, Melbourne, FL, USA Abstract: Osteogenesis imperfecta (OI, commonly known as brittle bone disease, is a genetic disease characterized by extreme bone fragility and consequent skeletal deformities. This connective tissue disorder is caused by mutations in the quality and quantity of the collagen that in turn affect the overall mechanical integrity of the bone, increasing its vulnerability to fracture. Animal models of the disease have played a critical role in the understanding of the pathology and causes of OI and in the investigation of a broad range of clinical therapies for the disease. Currently, at least 20 animal models have been officially recognized to represent the phenotype and biochemistry of the 17 different types of OI in humans. These include mice, dogs, and fish. Here, we describe each of the animal models and the type of OI they represent, and present their application in clinical research for treatments of OI, such as drug therapies (ie, bisphosphonates and sclerostin and mechanical (ie, vibrational loading. In the future, different dosages and lengths of treatment need to be further investigated on different animal models of OI using potentially promising treatments, such as cellular and chaperone therapies. A combination of therapies may also offer a viable treatment regime to improve bone quality and reduce fragility in animals before being introduced into clinical trials for OI patients. Keywords: OI, brittle bone, clinical research, mouse, dog, zebrafish

  18. Model systems to study immunomodulation in domestic food animals.

    Science.gov (United States)

    Roth, J A; Flaming, K P

    1990-01-01

    Development of immunomodulators for use in food producing animals is an active area of research. This research has generally incorporated aspects of immunosuppression in model systems. This methodology is appropriate because most of the research has been aimed at developing immunomodulators for certain economically significant diseases in which immunosuppression is believed to be an important component of their pathogenesis. The primary focus has been on stress-associated diseases (especially bovine respiratory disease), infectious diseases in young animals, and mastitis. The model systems used have limitations, but they have demonstrated that immunomodulators are capable of significantly increasing resistance to these important infectious disease syndromes. As our understanding of molecular immunology increases and as more potential immunomodulators become available, the use of relevant model systems should greatly aid advancement in the field of immunomodulation.

  19. Infantile Spasms: A Critical Review of Emerging Animal Models

    Science.gov (United States)

    Stafstrom, Carl E

    2009-01-01

    Infantile spasms is a developmental epilepsy syndrome with unique clinical and EEG features, a specific pattern of pharmacological responsiveness, and poor outcome in terms of cognition and epilepsy. Despite the devastating nature of infantile spasms, little is known about its pathogenesis. Until recently, there has been no animal model available to investigate the pathophysiology of the syndrome or to generate and test novel therapies. Now, several promising animal models have emerged, spanning the etiological spectrum from genetic causes (e.g., Down syndrome or Aristaless-related homeobox [ARX] mutation) to acquired causes (e.g., endogenous and exogenous toxins or stress hormones with convulsant activity or blockade of neural activity). These new models are discussed in this review, with emphasis on the insights each can provide for understanding, treating, and preventing infantile spasms. PMID:19471616

  20. Reproduction of an animal model of landmine blast injuries

    Directory of Open Access Journals (Sweden)

    Sen ZHANG

    2014-03-01

    Full Text Available Objective To reproduce an animal model of landmine blast injuries for studying its mechanism and characteristics. Methods Fifteen healthy New Zealand white rabbits (body weight 1.9-2.4 kg were prepared as experimental animals. Punctiform burster was used to simulate the landmine, and it was electrically detonated far away to produce landmine blast injuries on unilateral hind limb of rabbits in upright state. The vital signs before and 5min, 15min, 30min, 45min, 1h, 2h, 3h, 6h, 9h and 12h after injuries were recorded. Autopsy of dead animals was performed immediately and the survivors were sacrificed for pathological examination 6h and 12h after the injury. Macroscopic and microscopic changes in the injured limb and distant organs were observed. Fifteen random adult body weights were generated by random number table, and the explosive energy of M14 landmine (about 29g TNT explosive energy was simulated, to compare the ratio of explosive force equivalent to weight calculated between experimental animals and randomly selected adults. Results No significant change in blood pressure was observed at different time points before and after injuries. A broom-like change was found in the injured limb by the general observation. The subareas and pathological changes of injured limb coincided with the typical limb injuries produced by landmine explosion. Damage in different degrees was found in distant organs, and the wound characteristics and injury of major organs were in accordance with the reports of relevant literature. The ratio of explosive equivalent to weight of experimental animals (0.50±0.04g TNT/kg was similar to that of randomly selected adults (0.51±0.05g TNT/kg. Conclusion The present animal model could simulate the landmine explosive injuries, and may be used in research of landmine explosive injuries. DOI: 10.11855/j.issn.0577-7402.2014.01.14

  1. An animal model of spontaneous metabolic syndrome: Nile grass rat.

    Science.gov (United States)

    Noda, Kousuke; Melhorn, Mark I; Zandi, Souska; Frimmel, Sonja; Tayyari, Faryan; Hisatomi, Toshio; Almulki, Lama; Pronczuk, Andrzej; Hayes, K C; Hafezi-Moghadam, Ali

    2010-07-01

    Metabolic syndrome (MetS) is a prevalent and complex disease, characterized by the variable coexistence of obesity, dyslipidemia, hyperinsulinaemia, and hypertension. The alarming rise in the prevalence of metabolic disorders makes it imperative to innovate preventive or therapeutic measures for MetS and its complications. However, the elucidation of the pathogenesis of MetS has been hampered by the lack of realistic models. For example, the existing animal models of MetS, i.e., genetically engineered rodents, imitate certain aspects of the disease, while lacking other important components. Defining the natural course of MetS in a spontaneous animal model of the disease would be desirable. Here, we introduce the Nile grass rat (NGR), Arvicanthis niloticus, as a novel model of MetS. Studies of over 1100 NGRs in captivity, fed normal chow, revealed that most of these animals spontaneously develop dyslipidemia (P<0.01), and hyperglycemia (P<0.01) by 1 yr of age. Further characterization showed that the diabetic rats develop liver steatosis, abdominal fat accumulation, nephropathy, atrophy of pancreatic islets of Langerhans, fatty streaks in the aorta, and hypertension (P<0.01). Diabetic NGRs in the early phase of the disease develop hyperinsulinemia, and show a strong inverse correlation between plasma adiponectin and HbA1c levels (P<0.01). These data indicate that the NGR is a valuable, spontaneous model for exploring the etiology and pathophysiology of MetS as well as its various complications.

  2. The development and implementation of stroke risk prediction model in National Health Insurance Service's personal health record.

    Science.gov (United States)

    Lee, Jae-Woo; Lim, Hyun-Sun; Kim, Dong-Wook; Shin, Soon-Ae; Kim, Jinkwon; Yoo, Bora; Cho, Kyung-Hee

    2018-01-01

    The purpose of this study was to build a 10-year stroke prediction model and categorize a probability of stroke using the Korean national health examination data. Then it intended to develop the algorithm to provide a personalized warning on the basis of each user's level of stroke risk and a lifestyle correction message about the stroke risk factors. Subject to national health examinees in 2002-2003, the stroke prediction model identified when stroke was first diagnosed by following-up the cohort until 2013 and estimated a 10-year probability of stroke. It sorted the user's individual probability of stroke into five categories - normal, slightly high, high, risky, very risky, according to the five ranges of average probability of stroke in comparison to total population - less than 50 percentile, 50-70, 70-90, 90-99.9, more than 99.9 percentile, and constructed the personalized warning and lifestyle correction messages by each category. Risk factors in stroke risk model include the age, BMI, cholesterol, hypertension, diabetes, smoking status and intensity, physical activity, alcohol drinking, past history (hypertension, coronary heart disease) and family history (stroke, coronary heart disease). The AUC values of stroke risk prediction model from the external validation data set were 0.83 in men and 0.82 in women, which showed a high predictive power. The probability of stroke within 10 years for men in normal group (less than 50 percentile) was less than 3.92% and those in very risky group (top 0.01 percentile) was 66.2% and over. The women's probability of stroke within 10 years was less than 3.77% in normal group (less than 50 percentile) and 55.24% and over in very risky group. This study developed the stroke risk prediction model and the personalized warning and the lifestyle correction message based on the national health examination data and uploaded them to the personal health record service called My Health Bank in the health information website - Health

  3. Animal Modelling of Interstitial Cystitis/Bladder Pain Syndrome.

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    Birder, Lori; Andersson, Karl-Erik

    2018-01-01

    The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) remains elusive and may involve multiple causes. To better understand its pathophysiology, many efforts have been made to create IC/BPS models. Most existing models of IC/BPS strive to recreate bladder-related features by applying noxious intravesical or systemic stimuli to healthy animals. These models are useful to help understand various mechanisms; however, they are limited to demonstrating how the bladder and nervous system respond to noxious stimuli, and are not representative of the complex interactions and pathophysiology of IC/BPS. To study the various factors that may be relevant for IC/BPS, at least 3 different types of animal models are commonly used: (1) bladder-centric models, (2) models with complex mechanisms, and (3) psychological and physical stressors/natural disease models. It is obvious that all aspects of the human disease cannot be mimicked by a single model. It may be the case that several models, each contributing to a piece of the puzzle, are required to recreate a reasonable picture of the pathophysiology and time course of the disease(s) diagnosed as IC/BPS, and thus to identify reasonable targets for treatment.

  4. Sleep and Obesity: A focus on animal models

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    Mavanji, Vijayakumar; Billington, Charles J.; Kotz, Catherine M.; Teske, Jennifer A.

    2012-01-01

    The rapid rise in obesity prevalence in the modern world parallels a significant reduction in restorative sleep (Agras et al., 2004; Dixon et al., 2007; Dixon et al., 2001; Gangwisch and Heymsfield, 2004; Gupta et al., 2002; Sekine et al., 2002; Vioque et al., 2000; Wolk et al., 2003). Reduced sleep time and quality increases the risk for obesity, but the underlying mechanisms remain unclear (Gangwisch et al., 2005; Hicks et al., 1986; Imaki et al., 2002; Jennings et al., 2007; Moreno et al., 2006). A majority of the theories linking human sleep disturbances and obesity rely on self-reported sleep. However, studies with objective measurements of sleep/wake parameters suggest a U-shaped relationship between sleep and obesity. Studies in animal models are needed to improve our understanding of the association between sleep disturbances and obesity. Genetic and experimenter-induced models mimicking characteristics of human obesity are now available and these animal models will be useful in understanding whether sleep disturbances determine propensity for obesity, or result from obesity. These models exhibit weight gain profiles consistently different from control animals. Thus a careful evaluation of animal models will provide insight into the relationship between sleep disturbances and obesity in humans. In this review we first briefly consider the fundamentals of sleep and key sleep disturbances, such as sleep fragmentation and excessive daytime sleepiness (EDS), observed in obese individuals. Then we consider sleep deprivation studies and the role of circadian alterations in obesity. We describe sleep/wake changes in various rodent models of obesity and obesity resistance. Finally, we discuss possible mechanisms linking sleep disturbances with obesity. PMID:22266350

  5. Sex Differences in Animal Models: Focus on Addiction

    Science.gov (United States)

    Becker, Jill B.

    2016-01-01

    The purpose of this review is to discuss ways to think about and study sex differences in preclinical animal models. We use the framework of addiction, in which animal models have excellent face and construct validity, to illustrate the importance of considering sex differences. There are four types of sex differences: qualitative, quantitative, population, and mechanistic. A better understanding of the ways males and females can differ will help scientists design experiments to characterize better the presence or absence of sex differences in new phenomena that they are investigating. We have outlined major quantitative, population, and mechanistic sex differences in the addiction domain using a heuristic framework of the three established stages of the addiction cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Female rats, in general, acquire the self-administration of drugs and alcohol more rapidly, escalate their drug taking with extended access more rapidly, show more motivational withdrawal, and (where tested in animal models of “craving”) show greater reinstatement. The one exception is that female rats show less motivational withdrawal to alcohol. The bases for these quantitative sex differences appear to be both organizational, in that estradiol-treated neonatal animals show the male phenotype, and activational, in that the female phenotype depends on the effects of gonadal hormones. In animals, differences within the estrous cycle can be observed but are relatively minor. Such hormonal effects seem to be most prevalent during the acquisition of drug taking and less influential once compulsive drug taking is established and are linked largely to progesterone and estradiol. This review emphasizes not only significant differences in the phenotypes of females and males in the domain of addiction but emphasizes the paucity of data to date in our understanding of those differences. PMID:26772794

  6. Neural models on temperature regulation for cold-stressed animals

    Science.gov (United States)

    Horowitz, J. M.

    1975-01-01

    The present review evaluates several assumptions common to a variety of current models for thermoregulation in cold-stressed animals. Three areas covered by the models are discussed: signals to and from the central nervous system (CNS), portions of the CNS involved, and the arrangement of neurons within networks. Assumptions in each of these categories are considered. The evaluation of the models is based on the experimental foundations of the assumptions. Regions of the nervous system concerned here include the hypothalamus, the skin, the spinal cord, the hippocampus, and the septal area of the brain.

  7. Neuroprotective Effects of Oxytocin Hormone after an Experimental Stroke Model and the Possible Role of Calpain-1.

    Science.gov (United States)

    Etehadi Moghadam, Sepideh; Azami Tameh, Abolfazl; Vahidinia, Zeinab; Atlasi, Mohammad Ali; Hassani Bafrani, Hassan; Naderian, Homayoun

    2018-03-01

    Different mechanisms will be activated during ischemic stroke. Calpain proteases play a pivotal role in neuronal death after ischemia damage through apoptosis. Anti-apoptotic activities of the oxytocin (OT) in different ischemic tissues were reported in previous studies. Recently, a limited number of studies have noted the protective effects of OT in the brain. In the present study, the neuroprotective potential of OT in an animal model of transient middle cerebral artery occlusion (tMCAO) and the possible role of calpain-1 in the penumbra region were assessed. Adult male Wistar rats underwent 1 hour of tMCAO and were treated with nasal administration of OT. After 24 hours of reperfusion, infarct size was evaluated by triphenyltetrazolium chloride. Immunohistochemical staining and Western blotting were used to examine the expression of calpain-1. Nissl staining was performed for brain tissue morphology evaluation. OT reduced the infarct volume of the cerebral cortex and striatum compared with the ischemia control group significantly (P < .05). Calpain-1 overexpression, which was caused by ischemia, decreased after OT administration (P < .05). The number of pyknotic nuclei in neurons increased dramatically in the ischemic area and OT attenuated the apoptosis of neurons in the penumbra region (P < .01). We provided evidence for the neuroprotective role of OT after tMCAO through calpain-1 attenuation. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  8. Large Animal Models for Foamy Virus Vector Gene Therapy

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    Peter A. Horn

    2012-12-01

    Full Text Available Foamy virus (FV vectors have shown great promise for hematopoietic stem cell (HSC gene therapy. Their ability to efficiently deliver transgenes to multi-lineage long-term repopulating cells in large animal models suggests they will be effective for several human hematopoietic diseases. Here, we review FV vector studies in large animal models, including the use of FV vectors with the mutant O6-methylguanine-DNA methyltransferase, MGMTP140K to increase the number of genetically modified cells after transplantation. In these studies, FV vectors have mediated efficient gene transfer to polyclonal repopulating cells using short ex vivo transduction protocols designed to minimize the negative effects of ex vivo culture on stem cell engraftment. In this regard, FV vectors appear superior to gammaretroviral vectors, which require longer ex vivo culture to effect efficient transduction. FV vectors have also compared favorably with lentiviral vectors when directly compared in the dog model. FV vectors have corrected leukocyte adhesion deficiency and pyruvate kinase deficiency in the dog large animal model. FV vectors also appear safer than gammaretroviral vectors based on a reduced frequency of integrants near promoters and also near proto-oncogenes in canine repopulating cells. Together, these studies suggest that FV vectors should be highly effective for several human hematopoietic diseases, including those that will require relatively high percentages of gene-modified cells to achieve clinical benefit.

  9. Behavioral impairments in animal models for zinc deficiency

    Directory of Open Access Journals (Sweden)

    Simone eHagmeyer

    2015-01-01

    Full Text Available Apart from teratogenic and pathological effects of zinc deficiency such as the occurrence of skin lesions, anorexia, growth retardation, depressed wound healing, altered immune function, impaired night vision, and alterations in taste and smell acuity, characteristic behavioral changes in animal models and human patients suffering from zinc deficiency have been observed. Given that it is estimated that about 17% of the worldwide population are at risk for zinc deficiency and that zinc deficiency is associated with a variety of brain disorders and disease states in humans, it is of major interest to investigate, how these behavioral changes will affect the individual and a putative course of a disease. Thus, here, we provide a state of the art overview about the behavioral phenotypes observed in various models of zinc deficiency, among them environmentally produced zinc deficient animals as well as animal models based on a genetic alteration of a particular zinc homeostasis gene. Finally, we compare the behavioral phenotypes to the human condition of mild to severe zinc deficiency and provide a model, how zinc deficiency that is associated with many neurodegenerative and neuropsychological disorders might modify the disease pathologies.

  10. The Effect of Electromagnetic Field Treatment on Recovery from Ischemic Stroke in a Rat Stroke Model: Clinical, Imaging, and Pathological Findings

    Directory of Open Access Journals (Sweden)

    Y. Segal

    2016-01-01

    Full Text Available Stroke is a leading cause of death and disability. Effects of stroke include significant deficits in sensory-motor skills and cognitive abilities. At present, there are limited effective interventions for postacute stroke patients. In this preliminary research we studied a new noninvasive, very low intensity, low frequency, electromagnetic field treatment (VLIFE, targeting a neural network, on an in vivo stroke rat model. Eighteen rats were divided into three groups: sham (M1 and two treatment groups which were exposed to VLIFE treatment for 4 weeks, one using theta waves (M2 and another using beta waves (M3; all groups were followed up for an additional month. Results indicate that the M2 and M3 treated groups showed recovery of sensorimotor functional deficits, as demonstrated by Modified Neurological Severity Score and forelimb placement tests. Brain MRI imaging results show a decrease in perilesional edema and lateral ventricle widening in the treated groups. Fiber tracts’ imaging, following VLIFE treatment, showed a higher white matter integrity compared to control. Histological findings support neural regeneration processes. Our data suggest that VLIFE treatment, targeting a specific functional neural network by frequency rather than location, promotes neuronal plasticity after stroke and, as a result, improves clinical recovery. Further studies will investigate the full potential of the treatment.

  11. Relevance of animal models to human tardive dyskinesia

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    Blanchet Pierre J

    2012-03-01

    Full Text Available Abstract Tardive dyskinesia remains an elusive and significant clinical entity that can possibly be understood via experimentation with animal models. We conducted a literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous chewing movements constitute the most common pattern of expression of purposeless oral movements and represent an impermanent response, with individual and strain susceptibility differences. Transgenic mice are also used to address the contribution of adaptive and maladaptive signals induced during antipsychotic drug exposure. An emphasis on non-human primate modeling is proposed, and past experimental observations reviewed in various monkey species. Rodent and primate models are complementary, but the non-human primate model appears more convincingly similar to the human condition and better suited to address therapeutic issues against tardive dyskinesia.

  12. Modelling gait transition in two-legged animals

    Science.gov (United States)

    Pinto, Carla M. A.; Santos, Alexandra P.

    2011-12-01

    The study of locomotor patterns has been a major research goal in the last decades. Understanding how intralimb and interlimb coordination works out so well in animals' locomotion is a hard and challenging task. Many models have been proposed to model animal's rhythms. These models have also been applied to the control of rhythmic movements of adaptive legged robots, namely biped, quadruped and other designs. In this paper we study gait transition in a central pattern generator (CPG) model for bipeds, the 4-cells model. This model is proposed by Golubitsky, Stewart, Buono and Collins and is studied further by Pinto and Golubitsky. We briefly resume the work done by Pinto and Golubitsky. We compute numerically gait transition in the 4-cells CPG model for bipeds. We use Morris-Lecar equations and Wilson-Cowan equations as the internal dynamics for each cell. We also consider two types of coupling between the cells: diffusive and synaptic. We obtain secondary gaits by bifurcation of primary gaits, by varying the coupling strengths. Nevertheless, some bifurcating branches could not be obtained, emphasizing the fact that despite analytically those bifurcations exist, finding them is a hard task and requires variation of other parameters of the equations. We note that the type of coupling did not influence the results.

  13. Animal models of social anxiety disorder and their validity criteria.

    Science.gov (United States)

    Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Quevedo, João

    2014-09-26

    Anxiety disorders pose one of the largest threats to global mental health, and they predominantly emerge early in life. Social anxiety disorder, also known as social phobia, is the most common of all anxiety disorders. Moreover, it has severe consequences and is a disabling disorder that can cause an individual to be unable to perform the tasks of daily life. Social anxiety disorder is associated with the subsequent development of major depression and other mental diseases, as well as increased substance abuse. Although some neurobiological alterations have been found to be associated with social anxiety disorder, little is known about this disorder. Animal models are useful tools for the investigation of this disorder, as well as for finding new pharmacological targets for treatment. Thus, this review will highlight the main animal models of anxiety associated with social phobia. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Gender Differences in Animal Models of Posttraumatic Stress Disorder

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    Hagit Cohen

    2011-01-01

    Full Text Available Epidemiological studies report higher prevalence rates of stress-related disorders such as acute stress disorder and post-traumatic stress disorder (PTSD in women than in men following exposure to trauma. It is still not clear whether this greater prevalence in woman reflects a greater vulnerability to stress-related psychopathology. A number of individual and trauma-related characteristics have been hypothesized to contribute to these gender differences in physiological and psychological responses to trauma, differences in appraisal, interpretation or experience of threat, coping style or social support. In this context, the use of an animal model for PTSD to analyze some of these gender-related differences may be of particular utility. Animal models of PTSD offer the opportunity to distinguish between biological and socio-cultural factors, which so often enter the discussion about gender differences in PTSD prevalence.

  15. Altered glial plasticity in animal models for mood disorders.

    Science.gov (United States)

    Czéh, Boldizsár; Fuchs, Eberhard; Flügge, Gabriele

    2013-10-01

    Numerous clinical evidences support the notion that glial changes in fronto-limbic brain areas could contribute to the pathophysiology of mood disorders. Glial alterations have been reported not only in patients, but also in various kinds of animal models for depression. Molecular and cellular data suggest that all the major classes of glial cells are affected in these conditions, including astrocytes, oligodendrocytes, NG2-positive cells and microglia. The aim of this review was to summarize the currently available experimental results demonstrating alterations in glial morphology and functioning in animal models for mood disorders. Better understanding of these glial changes affecting neuronal activity could help us to identify novel targets for the development of antidepressant drugs.

  16. Cardiovascular Changes in Animal Models of Metabolic Syndrome

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    Alexandre M. Lehnen

    2013-01-01

    Full Text Available Metabolic syndrome has been defined as a group of risk factors that directly contribute to the development of cardiovascular disease and/or type 2 diabetes. Insulin resistance seems to have a fundamental role in the genesis of this syndrome. Over the past years to the present day, basic and translational research has used small animal models to explore the pathophysiology of metabolic syndrome and to develop novel therapies that might slow the progression of this prevalent condition. In this paper we discuss the animal models used for the study of metabolic syndrome, with particular focus on cardiovascular changes, since they are the main cause of death associated with the condition in humans.

  17. Animal models of tic disorders: a translational perspective.

    Science.gov (United States)

    Godar, Sean C; Mosher, Laura J; Di Giovanni, Giuseppe; Bortolato, Marco

    2014-12-30

    Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

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    Matthias Edinger

    1999-10-01

    Full Text Available Revealing the mechanisms of neoplastic disease and enhancing our ability to intervene in these processes requires an increased understanding of cellular and molecular changes as they occur in intact living animal models. We have begun to address these needs by developing a method of labeling tumor cells through constitutive expression of an optical reporter gene, noninvasively monitoring cellular proliferation in vivo using a sensitive photon detection system. A stable line of HeLa cells that expressed a modified firefly luciferase gene was generated, proliferation of these cells in irradiated severe combined immunodeficiency (SCID mice was monitored. Tumor cells were introduced into animals via subcutaneous, intraperitoneal and intravenous inoculation and whole body images, that revealed tumor location and growth kinetics, were obtained. The number of photons that were emitted from the labeled tumor cells and transmitted through murine tissues was sufficient to detect 1×103 cells in the peritoneal cavity, 1×104 cells at subcutaneous sites and 1×106 circulating cells immediately following injection. The kinetics of cell proliferation, as measured by photon emission, was exponential in the peritoneal cavity and at subcutaneous sites. Intravenous inoculation resulted in detectable colonies of tumor cells in animals receiving more than 1×103 cells. Our demonstrated ability to detect small numbers of tumor cells in living animals noninvasively suggests that therapies designed to treat minimal disease states, as occur early in the disease course and after elimination of the tumor mass, may be monitored using this approach. Moreover, it may be possible to monitor micrometastases and evaluate the molecular steps in the metastatic process. Spatiotemporal analyses of neoplasia will improve the predictability of animal models of human disease as study groups can be followed over time, this method will accelerate development of novel therapeutic

  19. NAFLD, Estrogens, and Physical Exercise: The Animal Model

    Directory of Open Access Journals (Sweden)

    Jean-Marc Lavoie

    2012-01-01

    Full Text Available One segment of the population that is particularly inclined to liver fat accumulation is postmenopausal women. Although nonalcoholic hepatic steatosis is more common in men than in women, after menopause there is a reversal in gender distribution. At the present time, weight loss and exercise are regarded as first line treatments for NAFLD in postmenopausal women, as it is the case for the management of metabolic syndrome. In recent years, there has been substantial evidence coming mostly from the use of the animal model, that indeed estrogens withdrawal is associated with modifications of molecular markers favouring the activity of metabolic pathways ultimately leading to liver fat accumulation. In addition, the use of the animal model has provided physiological and molecular evidence that exercise training provides estrogens-like protective effects on liver fat accumulation and its consequences. The purpose of the present paper is to present information relative to the development of a state of NAFLD resulting from the absence of estrogens and the role of exercise training, emphasizing on the contribution of the animal model on these issues.

  20. Stem cells in animal asthma models: a systematic review.

    Science.gov (United States)

    Srour, Nadim; Thébaud, Bernard

    2014-12-01

    Asthma control frequently falls short of the goals set in international guidelines. Treatment options for patients with poorly controlled asthma despite inhaled corticosteroids and long-acting β-agonists are limited, and new therapeutic options are needed. Stem cell therapy is promising for a variety of disorders but there has been no human clinical trial of stem cell therapy for asthma. We aimed to systematically review the literature regarding the potential benefits of stem cell therapy in animal models of asthma to determine whether a human trial is warranted. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal asthma models. Nineteen studies were selected. They were found to be heterogeneous in their design. Mesenchymal stromal cells were used before sensitization with an allergen, before challenge with the allergen and after challenge, most frequently with ovalbumin, and mainly in BALB/c mice. Stem cell therapy resulted in a reduction of bronchoalveolar lavage fluid inflammation and eosinophilia as well as Th2 cytokines such as interleukin-4 and interleukin-5. Improvement in histopathology such as peribronchial and perivascular inflammation, epithelial thickness, goblet cell hyperplasia and smooth muscle layer thickening was universal. Several studies showed a reduction in airway hyper-responsiveness. Stem cell therapy decreases eosinophilic and Th2 inflammation and is effective in several phases of the allergic response in animal asthma models. Further study is warranted, up to human clinical trials. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  1. Modeling DNA structure and processes through animation and kinesthetic visualizations

    Science.gov (United States)

    Hager, Christine

    There have been many studies regarding the effectiveness of visual aids that go beyond that of static illustrations. Many of these have been concentrated on the effectiveness of visual aids such as animations and models or even non-traditional visual aid activities like role-playing activities. This study focuses on the effectiveness of three different types of visual aids: models, animation, and a role-playing activity. Students used a modeling kit made of Styrofoam balls and toothpicks to construct nucleotides and then bond nucleotides together to form DNA. Next, students created their own animation to depict the processes of DNA replication, transcription, and translation. Finally, students worked in teams to build proteins while acting out the process of translation. Students were given a pre- and post-test that measured their knowledge and comprehension of the four topics mentioned above. Results show that there was a significant gain in the post-test scores when compared to the pre-test scores. This indicates that the incorporated visual aids were effective methods for teaching DNA structure and processes.

  2. Vestibular animal models: contributions to understanding physiology and disease.

    Science.gov (United States)

    Straka, Hans; Zwergal, Andreas; Cullen, Kathleen E

    2016-04-01

    Our knowledge of the vestibular sensory system, its functional significance for gaze and posture stabilization, and its capability to ensure accurate spatial orientation perception and spatial navigation has greatly benefitted from experimental approaches using a variety of vertebrate species. This review summarizes the attempts to establish the roles of semicircular canal and otolith endorgans in these functions followed by an overview of the most relevant fields of vestibular research including major findings that have advanced our understanding of how this system exerts its influence on reflexive and cognitive challenges encountered during daily life. In particular, we highlight the contributions of different animal models and the advantage of using a comparative research approach. Cross-species comparisons have established that the morpho-physiological properties underlying vestibular signal processing are evolutionarily inherent, thereby disclosing general principles. Based on the documented success of this approach, we suggest that future research employing a balanced spectrum of standard animal models such as fish/frog, mouse and primate will optimize our progress in understanding vestibular processing in health and disease. Moreover, we propose that this should be further supplemented by research employing more "exotic" species that offer unique experimental access and/or have specific vestibular adaptations due to unusual locomotor capabilities or lifestyles. Taken together this strategy will expedite our understanding of the basic principles underlying vestibular computations to reveal relevant translational aspects. Accordingly, studies employing animal models are indispensible and even mandatory for the development of new treatments, medication and technical aids (implants) for patients with vestibular pathologies.

  3. 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)

  4. Optical scatter imaging of cellular and mitochondrial swelling in brain tissue models of stroke

    Science.gov (United States)

    Johnson, Lee James

    2001-08-01

    The severity of brain edema resulting from a stroke can determine a patient's survival and the extent of their recovery. Cellular swelling is the microscopic source of a significant part of brain edema. Mitochondrial swelling also appears to be a determining event in the death or survival of the cells that are injured during a stroke. Therapies for reducing brain edema are not effective in many cases and current treatments of stroke do not address mitochondrial swelling at all. This dissertation is motivated by the lack of a complete understanding of cellular swelling resulting from stroke and the lack of a good method to begin to study mitochondrial swelling resulting from stroke in living brain tissue. In this dissertation, a novel method of detecting mitochondrial and cellular swelling in living hippocampal slices is developed and validated. The system is used to obtain spatial and temporal information about cellular and mitochondrial swelling resulting from various models of stroke. The effect of changes in water content on light scatter and absorption are examined in two models of brain edema. The results of this study demonstrate that optical techniques can be used to detect changes in water content. Mie scatter theory, the theoretical basis of the dual- angle scatter ratio imaging system, is presented. Computer simulations based on Mie scatter theory are used to determine the optimal angles for imaging. A detailed account of the early systems is presented to explain the motivations for the system design, especially polarization, wavelength and light path. Mitochondrial sized latex particles are used to determine the system response to changes in scattering particle size and concentration. The dual-angle scatter ratio imaging system is used to distinguish between osmotic and excitotoxic models of stroke injury. Such distinction cannot be achieved using the current techniques to study cellular swelling in hippocampal slices. The change in the scatter ratio is

  5. Multi-finger coordination in healthy subjects and stroke patients: a mathematical modelling approach

    Directory of Open Access Journals (Sweden)

    Ferrarin Maurizio

    2011-04-01

    Full Text Available Abstract Background Approximately 60% of stroke survivors experience hand dysfunction limiting execution of daily activities. Several methods have been proposed to objectively quantify fingers' joints range of motion (ROM, while few studies exist about multi-finger coordination during hand movements. The present work analysed this aspect, by providing a complete characterization of spatial and temporal aspects of hand movement, through the mathematical modelling of multi-joint finger motion in healthy subjects and stroke patients. Methods Hand opening and closing movements were examined in 12 healthy volunteers and 14 hemiplegic stroke survivors by means of optoelectronic kinematic analysis. The flexion/extension angles of metacarpophalangeal (MCPJ and proximal interphalangeal joints (IPJ of all fingers were computed and mathematically characterized by a four-parameter hyperbolic tangent function. Accuracy of the selected model was analysed by means of coefficient of determination (R2 and root mean square error (RMSE. Test-retest reliability was quantified by intraclass correlation coefficient (ICC and test-retest errors. Comparison between performances of healthy controls and stroke subjects were performed by analysing possible differences in parameters describing angular and temporal aspects of hand kinematics and inter-joint, inter-digit coordination. Results The angular profiles of hand opening and closing were accurately characterized by the selected model, both in healthy controls and in stroke subjects (R2 > 0.973, RMSE 0.75 and remarking errors comparable to those obtained with other methods. Comparison with healthy controls revealed that hemiparetic hand movement was impaired not only in joints ROM but also in the temporal aspects of motion: peak velocities were significantly decreased, inter-digit coordination was reduced of more than 50% and inter-joint coordination patterns were highly disrupted. In particular, the stereotypical

  6. Multi-finger coordination in healthy subjects and stroke patients: a mathematical modelling approach.

    Science.gov (United States)

    Carpinella, Ilaria; Jonsdottir, Johanna; Ferrarin, Maurizio

    2011-04-20

    Approximately 60% of stroke survivors experience hand dysfunction limiting execution of daily activities. Several methods have been proposed to objectively quantify fingers' joints range of motion (ROM), while few studies exist about multi-finger coordination during hand movements. The present work analysed this aspect, by providing a complete characterization of spatial and temporal aspects of hand movement, through the mathematical modelling of multi-joint finger motion in healthy subjects and stroke patients. Hand opening and closing movements were examined in 12 healthy volunteers and 14 hemiplegic stroke survivors by means of optoelectronic kinematic analysis. The flexion/extension angles of metacarpophalangeal (MCPJ) and proximal interphalangeal joints (IPJ) of all fingers were computed and mathematically characterized by a four-parameter hyperbolic tangent function. Accuracy of the selected model was analysed by means of coefficient of determination (R2) and root mean square error (RMSE). Test-retest reliability was quantified by intraclass correlation coefficient (ICC) and test-retest errors. Comparison between performances of healthy controls and stroke subjects were performed by analysing possible differences in parameters describing angular and temporal aspects of hand kinematics and inter-joint, inter-digit coordination. The angular profiles of hand opening and closing were accurately characterized by the selected model, both in healthy controls and in stroke subjects (R2 > 0.973, RMSE 0.75 and remarking errors comparable to those obtained with other methods. Comparison with healthy controls revealed that hemiparetic hand movement was impaired not only in joints ROM but also in the temporal aspects of motion: peak velocities were significantly decreased, inter-digit coordination was reduced of more than 50% and inter-joint coordination patterns were highly disrupted. In particular, the stereotypical proximal-to-distal opening sequence (reversed during

  7. Thrombolytic and anticoagulation treatment in a rat embolic stroke model

    DEFF Research Database (Denmark)

    Rasmussen, Rune Skovgaard; Overgaard, K; Meden, P

    2003-01-01

    and assigned to: (i). controls, (ii). rt-PA 6 mg/kg, (iii). PENTA 0.5 mg/kg, (iv). PENTA 0.5 mg/kg and rt-PA 6 mg/kg. After 2 days animals were killed, the brains removed and evaluated microscopically. RESULTS: The median infarct size measured in percentage of the affected hemisphere was 25% in the control...

  8. Testing flow diversion in animal models: a systematic review.

    Science.gov (United States)

    Fahed, Robert; Raymond, Jean; Ducroux, Célina; Gentric, Jean-Christophe; Salazkin, Igor; Ziegler, Daniela; Gevry, Guylaine; Darsaut, Tim E

    2016-04-01

    Flow diversion (FD) is increasingly used to treat intracranial aneurysms. We sought to systematically review published studies to assess the quality of reporting and summarize the results of FD in various animal models. Databases were searched to retrieve all animal studies on FD from 2000 to 2015. Extracted data included species and aneurysm models, aneurysm and neck dimensions, type of flow diverter, occlusion rates, and complications. Articles were evaluated using a checklist derived from the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Forty-two articles reporting the results of FD in nine different aneurysm models were included. The rabbit elastase-induced aneurysm model was the most commonly used, with 3-month occlusion rates of 73.5%, (95%CI [61.9-82.6%]). FD of surgical sidewall aneurysms, constructed in rabbits or canines, resulted in high occlusion rates (100% [65.5-100%]). FD resulted in modest occlusion rates (15.4% [8.9-25.1%]) when tested in six complex canine aneurysm models designed to reproduce more difficult clinical contexts (large necks, bifurcation, or fusiform aneurysms). Adverse events, including branch occlusion, were rarely reported. There were no hemorrhagic complications. Articles complied with 20.8 ± 3.9 of 41 ARRIVE items; only a small number used randomization (3/42 articles [7.1%]) or a control group (13/42 articles [30.9%]). Preclinical studies on FD have shown various results. Occlusion of elastase-induced aneurysms was common after FD. The model is not challenging but standardized in many laboratories. Failures of FD can be reproduced in less standardized but more challenging surgical canine constructions. The quality of reporting could be improved.

  9. Acute liver failure: a critical appraisal of available animal models.

    Science.gov (United States)

    Bélanger, Mireille; Butterworth, Roger F

    2005-12-01

    The availability of adequate experimental models of acute liver failure (ALF) is of prime importance to provide a better understanding of this condition and allow the development and testing of new therapeutic approaches for patients with ALF. However, the numerous etiologies and complications of ALF contribute to the complexity of this condition and render the development of an ideal experimental model of ALF more difficult than expected. Instead, a number of different models that may be used for the study of specific aspects of ALF have been developed. The most common approaches used to induce ALFin experimental animals are surgical procedures, toxic liver injury,or a combination of both. Despite the high prevalence of viral hepatitis worldwide, very few satisfactory viral models of ALF are available. Established and newly developed models of ALF are reviewed.

  10. Melittin restores proteasome function in an animal model of ALS

    Directory of Open Access Journals (Sweden)

    Lee Sang Min

    2011-06-01

    Full Text Available Abstract Amyotrophic lateral sclerosis (ALS is a paralyzing disorder characterized by the progressive degeneration and death of motor neurons and occurs both as a sporadic and familial disease. Mutant SOD1 (mtSOD1 in motor neurons induces vulnerability to the disease through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport- and growth factor signaling, excitotoxicity, and neuro-inflammation. Melittin is a 26 amino acid protein and is one of the components of bee venom which is used in traditional Chinese medicine to inhibit of cancer cell proliferation and is known to have anti-inflammatory and anti-arthritic effects. The purpose of the present study was to determine if melittin could suppress motor neuron loss and protein misfolding in the hSOD1G93A mouse, which is commonly used as a model for inherited ALS. Meltittin was injected at the 'ZuSanLi' (ST36 acupuncture point in the hSOD1G93A animal model. Melittin-treated animals showed a decrease in the number of microglia and in the expression level of phospho-p38 in the spinal cord and brainstem. Interestingly, melittin treatment in symptomatic ALS animals improved motor function and reduced the level of neuron death in the spinal cord when compared to the control group. Furthermore, we found increased of α-synuclein modifications, such as phosphorylation or nitration, in both the brainstem and spinal cord in hSOD1G93A mice. However, melittin treatment reduced α-synuclein misfolding and restored the proteasomal activity in the brainstem and spinal cord of symptomatic hSOD1G93A transgenic mice. Our research suggests a potential functional link between melittin and the inhibition of neuroinflammation in an ALS animal model.

  11. Stroke Treatments

    Science.gov (United States)

    ... Month Infographic Stroke Hero F.A.S.T. Quiz Stroke Treatment Stroke used to rank fourth in leading causes of ... type of treatment depends on the type of stroke. Ischemic stroke happens when a clot blocks a ...

  12. PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model.

    Science.gov (United States)

    Low, Pei Ching; Manzanero, Silvia; Mohannak, Nika; Narayana, Vinod K; Nguyen, Tam H; Kvaskoff, David; Brennan, Faith H; Ruitenberg, Marc J; Gelderblom, Mathias; Magnus, Tim; Kim, Hyun Ah; Broughton, Brad R S; Sobey, Christopher G; Vanhaesebroeck, Bart; Stow, Jennifer L; Arumugam, Thiruma V; Meunier, Frédéric A

    2014-03-14

    Stroke is a major cause of death worldwide and the leading cause of permanent disability. Although reperfusion is currently used as treatment, the restoration of blood flow following ischaemia elicits a profound inflammatory response mediated by proinflammatory cytokines such as tumour necrosis factor (TNF), exacerbating tissue damage and worsening the outcomes for stroke patients. Phosphoinositide 3-kinase delta (PI3Kδ) controls intracellular TNF trafficking in macrophages and therefore represents a prospective target to limit neuroinflammation. Here we show that PI3Kδ inhibition confers protection in ischaemia/reperfusion models of stroke. In vitro, restoration of glucose supply following an episode of glucose deprivation potentiates TNF secretion from primary microglia-an effect that is sensitive to PI3Kδ inhibition. In vivo, transient middle cerebral artery occlusion and reperfusion in kinase-dead PI3Kδ (p110δ(D910A/D910A)) or wild-type mice pre- or post-treated with the PI3Kδ inhibitor CAL-101, leads to reduced TNF levels, decreased leukocyte infiltration, reduced infarct size and improved functional outcome. These data identify PI3Kδ as a potential therapeutic target in ischaemic stroke.

  13. Modeling the Cost Effectiveness of Neuroimaging-Based Treatment of Acute Wake-Up Stroke.

    Directory of Open Access Journals (Sweden)

    Ankur Pandya

    Full Text Available Thrombolytic treatment (tissue-type plasminogen activator [tPA] is only recommended for acute ischemic stroke patients with stroke onset time 4.5 hours, 46.3% experienced a good stroke outcome. Lifetime discounted QALYs and costs were 5.312 and $88,247 for the no treatment strategy and 5.342 and $90,869 for the MRI-based strategy, resulting in an ICER of $88,000/QALY. Results were sensitive to variations in patient- and provider-specific factors such as sleep duration, hospital travel and door-to-needle times, as well as onset probability distribution, MRI specificity, and mRS utility values.Our model-based findings suggest that an MRI-based treatment strategy for this population could be cost-effective and quantifies the impact that patient- and provider-specific factors, such as sleep duration, hospital travel and door-to-needle times, could have on the optimal decision for wake-up stroke patients.

  14. Themes and strategies for studying the biology of stroke recovery in the poststroke epoch.

    Science.gov (United States)

    Carmichael, S Thomas

    2008-04-01

    This review will focus on the emerging principles of neural repair after stroke, and on the overlap between cellular mechanisms of neural repair in stroke and clinical principles of recovery and rehabilitation. Stroke induces axonal sprouting and neurogenesis. Axonal sprouting occurs in tissue adjacent to the stroke and its connected cortical areas, and from sites that are contralateral to the infarct. Neurogenesis produces newly born immature neurons in peri-infarct striatum and cortex. Stimulation of both axonal sprouting and neurogenesis is associated with improved recovery in animal models of stroke. A unique cellular environment in the poststroke brain supports neural repair: an association of angiogenic and remodeling blood vessels with newly born immature neurons in a neurovasclar niche. Controversies in the field of neural repair after stroke persist, and relate to the locations of axonal sprouting in animal models of stroke and how these correlate to patterns of human remapping and recovery, and to the different models of stroke used in studies of neurogenesis. On a cellular level, the phenomenology of neural repair after stroke has been defined and unique regenerative environments in the poststroke brain identified. As the field moves toward specific studies of causal mechanisms in poststroke repair, it will need to maintain a perspective of the animal models suited to the study of neural repair after stroke as they relate to the patterns of recovery in humans in this disease.

  15. Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome

    DEFF Research Database (Denmark)

    Sangild, Per Torp; Ney, Denise M; Sigalet, David L

    2014-01-01

    help but careful evaluation of the cellular mechanisms, safety and translational relevance of new procedures are required. Distal intestinal resection, without a functioning colon, results in the most severe complications and adaptation may depend on the age at resection (preterm, term, young, adult...... hormone, insulin-like growth factor 1, epidermal growth factor, keratinocyte growth factor). The greater size of rats, and especially young pigs, is an advantage for testing surgical procedures and nutritional interventions (e.g. PN, milk diets, long/short chain lipids, pre- and probiotics). Conversely......, newborn pigs and weanling rats represent a translational advantage for infant SBS due to their immature intestine. A balance among practical, economical, experimental and ethical constraints determines the choice of SBS model for each clinical or basic research question....

  16. Biochemical correlates in an animal model of depression

    International Nuclear Information System (INIS)

    Johnson, J.O.

    1986-01-01

    A valid animal model of depression was used to explore specific adrenergic receptor differences between rats exhibiting aberrant behavior and control groups. Preliminary experiments revealed a distinct upregulation of hippocampal beta-receptors (as compared to other brain regions) in those animals acquiring a response deficit as a result of exposure to inescapable footshock. Concurrent studies using standard receptor binding techniques showed no large changes in the density of alpha-adrenergic, serotonergic, or dopaminergic receptor densities. This led to the hypothesis that the hippocampal beta-receptor in responses deficient animals could be correlated with the behavioral changes seen after exposure to the aversive stimulus. Normalization of the behavior through the administration of antidepressants could be expected to reverse the biochemical changes if these are related to the mechanism of action of antidepressant drugs. This study makes three important points: (1) there is a relevant biochemical change in the hippocampus of response deficient rats which occurs in parallel to a well-defined behavior, (2) the biochemical and behavioral changes are normalized by antidepressant treatments exhibiting both serotonergic and adrenergic mechanisms of action, and (3) the mode of action of antidepressants in this model is probably a combination of serotonergic and adrenergic influences modulating the hippocampal beta-receptor. These results are discussed in relation to anatomical and biochemical aspects of antidepressant action

  17. Improved animal models for testing gene therapy for atherosclerosis.

    Science.gov (United States)

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

    2014-04-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

  18. Basic mechanisms of catastrophic epilepsy – overview from animal models

    Science.gov (United States)

    Galanopoulou, Aristea S.

    2013-01-01

    Infantile spasms are age-specific seizures of infantile epileptic encephalopathies that are usually associated with poor epilepsy and neurodevelopmental outcomes. The current treatments are not always effective and may be associated with significant side effects. Various mechanisms have been proposed as pathogenic for infantile spasms, including cortical or brainstem dysfunction, disruption of normal cortical-subcortical communications, genetic defects, inflammation, stress, developmental abnormalities. Many of these have been recently tested experimentally, resulting into the emergence of several animal models of infantile spasms. The stress theory of spasms yielded the corticotropin releasing hormone (CRH) induced model, which showed the higher proconvulsant potency of CRH in developing rats, although only limbic seizures were observed. Models of acute induction of infantile spasms in rodents include the N-methyl-D-aspartate (NMDA) model of emprosthotonic seizures, the prenatal betamethasone and prenatal stress variants of the NMDA model, and the γ-butyrolactone induced spasms in a Down’s syndrome mouse model. Chronic rodent models of infantile spasms include the tetrodotoxin model and the multiple-hit models in rats, as well as two genetic mouse models of interneuronopathies with infantile spasms due to loss of function of the aristaless X-linked homeobox related gene (ARX). This review discusses the emerging mechanisms for generation of infantile spasms and their associated chronic epileptic and dyscognitive phenotype as well as the recent progress in identifying pathways to better treat this epileptic encephalopathy. PMID:23312951

  19. Cardiovascular effects of epinephrine during rewarming from hypothermia in an intact animal model.

    Science.gov (United States)

    Kondratiev, T V; Myhre, E S P; Simonsen, O; Nymark, T-B; Tveita, T

    2006-02-01

    Rewarming from accidental hypothermia is often complicated by "rewarming shock," characterized by low cardiac output (CO) and a sudden fall in peripheral arterial pressure. In this study, we tested whether epinephrine (Epi) is able to prevent rewarming shock when given intravenously during rewarming from experimental hypothermia in doses tested to elevate CO and induce vasodilation, or lack of vasodilation, during normothermia. A rat model designed for circulatory studies during experimental hypothermia and rewarming was used. A total of six groups of animals were used: normothermic groups 1, 2, and 3 for dose-finding studies, and hypothermic groups 4, 5, and 6. At 20 and 24 degrees C during rewarming, group 4 (low-dose Epi) and group 5 (high-dose Epi) received bolus injections of 0.1 and 1.0 microg Epi, respectively. At 28 degrees C, Epi infusion was started in groups 4 and 5 with 0.125 and 1.25 microg/min, respectively. Group 6 served as saline control. After rewarming, both CO and stroke volume were restored in group 4, in contrast to groups 5 and 6, in which both CO and stroke volume remained significantly reduced (30%). Total peripheral resistance was significantly higher in group 5 during rewarming from 24 to 34 degrees C, compared with groups 4 and 6. This study shows that, in contrast to normothermic conditions, Epi infused during hypothermia induces vasoconstriction rather than vasodilation combined with lack of CO elevation. The apparent dissociation between myocardial and vascular responses to Epi at low temperatures may be related to hypothermia-induced myocardial failure and changes in temperature-dependent adrenoreceptor affinity.

  20. Development of virtual hands using animation software and graphical modelling

    International Nuclear Information System (INIS)

    Oliveira, Erick da S.; Junior, Alberico B. de C.

    2016-01-01

    The numerical dosimetry uses virtual anthropomorphic simulators to represent the human being in computational framework and thus assess the risks associated with exposure to a radioactive source. With the development of computer animation software, the development of these simulators was facilitated using only knowledge of human anatomy to prepare various types of simulators (man, woman, child and baby) in various positions (sitting, standing, running) or part thereof (head, trunk and limbs). These simulators are constructed by loops of handling and due to the versatility of the method, one can create various geometries irradiation was not possible before. In this work, we have built an exhibition of a radiopharmaceutical scenario manipulating radioactive material using animation software and graphical modeling and anatomical database. (author)

  1. Animal models of gene-environment interactions in schizophrenia.

    Science.gov (United States)

    Ayhan, Yavuz; Sawa, Akira; Ross, Christopher A; Pletnikov, Mikhail V

    2009-12-07

    The pathogenesis of schizophrenia and related mental illnesses likely involves multiple interactions between susceptibility genes of small effects and environmental factors. Gene-environment interactions occur across different stages of neurodevelopment to produce heterogeneous clinical and pathological manifestations of the disease. The main obstacle for mechanistic studies of gene-environment interplay has been the paucity of appropriate experimental systems for elucidating the molecular pathways that mediate gene-environment interactions relevant to schizophrenia. Recent advances in psychiatric genetics and a plethora of experimental data from animal studies allow us to suggest a new approach to gene-environment interactions in schizophrenia. We propose that animal models based on identified genetic mutations and measurable environment factors will help advance studies of the molecular mechanisms of gene-environment interplay.

  2. Large animal models and new therapies for glycogen storage disease.

    Science.gov (United States)

    Brooks, Elizabeth D; Koeberl, Dwight D

    2015-05-01

    Glycogen storage diseases (GSD), a unique category of inherited metabolic disorders, were first described early in the twentieth century. Since then, the biochemical and genetic bases of these disorders have been determined, and an increasing number of animal models for GSD have become available. At least seven large mammalian models have been developed for laboratory research on GSDs. These models have facilitated the development of new therapies, including gene therapy, which are undergoing clinical translation. For example, gene therapy prolonged survival and prevented hypoglycemia during fasting for greater than one year in dogs with GSD type Ia, and the need for periodic re-administration to maintain efficacy was demonstrated in that dog model. The further development of gene therapy could provide curative therapy for patients with GSD and other inherited metabolic disorders.

  3. Establishment of animal model of dual liver transplantation in rat.

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    Full Text Available The animal model of the whole-size and reduced-size liver transplantation in both rat and mouse has been successfully established. Because of the difficulties and complexities in microsurgical technology, the animal model of dual liver transplantation was still not established for twelve years since the first human dual liver transplantation has been made a success. There is an essential need to establish this animal model to lay a basic foundation for clinical practice. To study the physiological and histopathological changes of dual liver transplantation, "Y" type vein from the cross part between vena cava and two iliac of donor and "Y' type prosthesis were employed to recanalize portal vein and the bile duct between dual liver grafts and recipient. The dual right upper lobes about 45-50% of the recipient liver volume were taken as donor, one was orthotopically implanted at its original position, the other was rotated 180° sagitally and heterotopically positioned in the left upper quadrant. Microcirculation parameters, liver function, immunohistochemistry and survival were analyzed to evaluate the function of dual liver grafts. No significant difference in the hepatic microcirculatory flow was found between two grafts in the first 90 minutes after reperfusion. Light and electronic microscope showed the liver architecture was maintained without obvious features of cellular destruction and the continuity of the endothelium was preserved. Only 3 heterotopically positioned graft appeared patchy desquamation of endothelial cell, mitochondrial swelling and hepatocytes cytoplasmic vacuolization. Immunohistochemistry revealed there is no difference in hepatocyte activity and the ability of endothelia to contract and relax after reperfusion between dual grafts. Dual grafts made a rapid amelioration of liver function after reperfusion. 7 rats survived more than 7 days with survival rate of 58.3.%. Using "Y" type vein and bile duct prosthesis, we

  4. Current understanding of hypospadias: relevance of animal models.

    Science.gov (United States)

    Cunha, Gerald R; Sinclair, Adriane; Risbridger, Gail; Hutson, John; Baskin, Laurence S

    2015-05-01

    Hypospadias is a congenital abnormality of the penile urethra with an incidence of approximately 1:200-1:300 male births, which has doubled over the past three decades. The aetiology of the overwhelming majority of hypospadias remains unknown but appears to be a combination of genetic susceptibility and prenatal exposure to endocrine disruptors. Reliable animal models of hypospadias are required for better understanding of the mechanisms of normal penile urethral formation and hence hypospadias. Mice and/or rats are generally used for experimental modelling of hypospadias, however these do not fully reflect the human condition. To use these models successfully, researchers must understand the similarities and differences between mouse, rat and human penile anatomy as well as the normal morphogenetic mechanisms of penile development in these species. Despite some important differences, numerous features of animal and human hypospadias are shared: the prevalence of distal penile malformations; disruption of the urethral meatus; disruption of urethra-associated erectile bodies; and a common mechanism of impaired epithelial fusion events. Rat and mouse models of hypospadias are crucial to our understanding of hypospadias to ultimately reduce its incidence through better preventive strategies.

  5. Understanding the Pathogenesis of Angelman Syndrome through Animal Models

    Directory of Open Access Journals (Sweden)

    Nihar Ranjan Jana

    2012-01-01

    Full Text Available Angelman syndrome (AS is a neurodevelopmental disorder characterized by severe mental retardation, lack of speech, ataxia, susceptibility to seizures, and unique behavioral features such as easily provoked smiling and laughter and autistic features. The disease is primarily caused by deletion or loss-of-function mutations of the maternally inherited UBE3A gene located within chromosome 15q11-q13. The UBE3A gene encodes a 100 kDa protein that functions as ubiquitin ligase and transcriptional coactivator. Emerging evidence now indicates that UBE3A plays a very important role in synaptic function and in regulation of activity-dependent synaptic plasticity. A number of animal models for AS have been generated to understand the disease pathogenesis. The most widely used model is the UBE3A-maternal-deficient mouse that recapitulates most of the essential features of AS including cognitive and motor abnormalities. This paper mainly discusses various animal models of AS and how these models provide fundamental insight into understanding the disease biology for potential therapeutic intervention.

  6. Understanding the Pathogenesis of Angelman Syndrome through Animal Models

    Science.gov (United States)

    Jana, Nihar Ranjan

    2012-01-01

    Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe mental retardation, lack of speech, ataxia, susceptibility to seizures, and unique behavioral features such as easily provoked smiling and laughter and autistic features. The disease is primarily caused by deletion or loss-of-function mutations of the maternally inherited UBE3A gene located within chromosome 15q11-q13. The UBE3A gene encodes a 100 kDa protein that functions as ubiquitin ligase and transcriptional coactivator. Emerging evidence now indicates that UBE3A plays a very important role in synaptic function and in regulation of activity-dependent synaptic plasticity. A number of animal models for AS have been generated to understand the disease pathogenesis. The most widely used model is the UBE3A-maternal-deficient mouse that recapitulates most of the essential features of AS including cognitive and motor abnormalities. This paper mainly discusses various animal models of AS and how these models provide fundamental insight into understanding the disease biology for potential therapeutic intervention. PMID:22830052

  7. Research on lightning stroke model and characteristics of electronic transformer

    Directory of Open Access Journals (Sweden)

    Li Mu

    2018-01-01

    Full Text Available In order to improve the reliability of power supply, a large number of electronic voltage and current transformers are used in digital substations. In this paper, the mathematical model of the electronic transformer is analyzed firstly, and its circuit model is given. According to the difference of working characteristics between voltage transformer and current transformer, the circuit model of voltage type electronic transformer and current type electronic transformer is given respectively. By analyzing their broadband transmission characteristics, the accuracy of the model is verified, and their lightning analysis models are obtained.

  8. Neuroserpin polymorphisms and stroke risk in a biracial population: the stroke prevention in young women study

    Directory of Open Access Journals (Sweden)

    Stern Barney J

    2007-10-01

    Full Text Available Abstract Background Neuroserpin, primarily localized to CNS neurons, inhibits the adverse effects of tissue-type plasminogen activator (tPA on the neurovascular unit and has neuroprotective effects in animal models of ischemic stroke. We sought to evaluate the association of neuroserpin polymorphisms with risk for ischemic stroke among young women. Methods A population-based case-control study of stroke among women aged 15–49 identified 224 cases of first ischemic stroke (47.3% African-American and 211 age-matched control subjects (43.1% African-American. Neuroserpin single nucleotide polymorphisms (SNPs chosen through HapMap were genotyped in the study population and assessed for association with stroke. Results Of the five SNPs analyzed, the A allele (frequency; Caucasian = 0.56, African-American = 0.42 of SNP rs6797312 located in intron 1 was associated with stroke in an age-adjusted dominant model (AA and AT vs. TT among Caucasians (OR = 2.05, p = 0.023 but not African-Americans (OR = 0.71, p = 0.387. Models adjusting for other risk factors strengthened the association. Race-specific haplotype analyses, inclusive of SNP rs6797312, again demonstrated significant associations with stroke among Caucasians only. Conclusion This study provides the first evidence that neuroserpin is associated with early-onset ischemic stroke among Caucasian women.

  9. Heat transfer modeling in exhaust systems of high-performance two-stroke engines

    OpenAIRE

    Lujan Martinez, José Manuel; Climent Puchades, Héctor; Olmeda González, Pablo Cesar; JIMENEZ MACEDO, VICTOR DANIEL

    2014-01-01

    Heat transfer from the hot gases to the wall in exhaust systems of high-performance two-stroke engines is underestimated using steady state with fully developed flow empirical correlations. This fact is detected when comparing measured and modeled pressure pulses in different positions in the exhaust system. This can be explained taking into account that classical expressions have been validated for fully developed flows, a situation that is far from the flow behavior in reciprocating interna...

  10. Stroke: Working toward a Prioritized World Agenda

    Science.gov (United States)

    Hachinski, Vladimir; Donnan, Geoffrey A.; Gorelick, Philip B.; Hacke, Werner; Cramer, Steven C.; Kaste, Markku; Fisher, Marc; Brainin, Michael; Buchan, Alastair M.; Lo, Eng H.; Skolnick, Brett E.; Furie, Karen L.; Hankey, Graeme J.; Kivipelto, Miia; Morris, John; Rothwell, Peter M.; Sacco, Ralph L.; Smith, Jr., Sidney C.; Wang, Yulun; Bryer, Alan; Ford, Gary A.; Iadecola, Costantino; Martins, Sheila C.O.; Saver, Jeff; Skvortsova, Veronika; Bayley, Mark; Bednar, Martin M.; Duncan, Pamela; Enney, Lori; Finklestein, Seth; Jones, Theresa A.; Kalra, Lalit; Kleim, Jeff; Nitkin, Ralph; Teasell, Robert; Weiller, Cornelius; Desai, Bhupat; Goldberg, Mark P.; Heiss, Wolf-Dieter; Saarelma, Osmo; Schwamm, Lee H.; Shinohara, Yukito; Trivedi, Bhargava; Wahlgren, Nils; Wong, Lawrence K.; Hakim, Antoine; Norrving, Bo; Prudhomme, Stephen; Bornstein, Natan M.; Davis, Stephen M.; Goldstein, Larry B.; Leys, Didier; Tuomilehto, Jaakko

    2010-01-01

    Background and Purpose The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Methods Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Results Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent ‘silo’ mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (e.g., social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build

  11. Stroke: working toward a prioritized world agenda.

    Science.gov (United States)

    Hachinski, Vladimir; Donnan, Geoffrey A; Gorelick, Philip B; Hacke, Werner; Cramer, Steven C; Kaste, Markku; Fisher, Marc; Brainin, Michael; Buchan, Alastair M; Lo, Eng H; Skolnick, Brett E; Furie, Karen L; Hankey, Graeme J; Kivipelto, Miia; Morris, John; Rothwell, Peter M; Sacco, Ralph L; Smith, Sidney C; Wang, Yulun; Bryer, Alan; Ford, Gary A; Iadecola, Costantino; Martins, Sheila C O; Saver, Jeff; Skvortsova, Veronika; Bayley, Mark; Bednar, Martin M; Duncan, Pamela; Enney, Lori; Finklestein, Seth; Jones, Theresa A; Kalra, Lalit; Kleim, Jeff; Nitkin, Ralph; Teasell, Robert; Weiller, Cornelius; Desai, Bhupat; Goldberg, Mark P; Heiss, Wolf-Dieter; Saarelma, Osmo; Schwamm, Lee H; Shinohara, Yukito; Trivedi, Bhargava; Wahlgren, Nils; Wong, Lawrence K; Hakim, Antoine; Norrving, Bo; Prudhomme, Stephen; Bornstein, Natan M; Davis, Stephen M; Goldstein, Larry B; Leys, Didier; Tuomilehto, Jaakko

    2010-08-01

    The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Preliminary work was performed by seven working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and

  12. Zebrafish: an animal model for research in veterinary medicine.

    Science.gov (United States)

    Nowik, N; Podlasz, P; Jakimiuk, A; Kasica, N; Sienkiewicz, W; Kaleczyc, J

    2015-01-01

    The zebrafish (Danio rerio) has become known as an excellent model organism for studies of vertebrate biology, vertebrate genetics, embryonal development, diseases and drug screening. Nevertheless, there is still lack of detailed reports about usage of the zebrafish as a model in veterinary medicine. Comparing to other vertebrates, they can lay hundreds of eggs at weekly intervals, externally fertilized zebrafish embryos are accessible to observation and manipulation at all stages of their development, which makes possible to simplify the research techniques such as fate mapping, fluorescent tracer time-lapse lineage analysis and single cell transplantation. Although zebrafish are only 2.5 cm long, they are easy to maintain. Intraperitoneal and intracerebroventricular injections, blood sampling and measurement of food intake are possible to be carry out in adult zebrafish. Danio rerio is a useful animal model for neurobiology, developmental biology, drug research, virology, microbiology and genetics. A lot of diseases, for which the zebrafish is a perfect model organism, affect aquatic animals. For a part of them, like those caused by Mycobacterium marinum or Pseudoloma neutrophila, Danio rerio is a natural host, but the zebrafish is also susceptible to the most of fish diseases including Itch, Spring viraemia of carp and Infectious spleen and kidney necrosis. The zebrafish is commonly used in research of bacterial virulence. The zebrafish embryo allows for rapid, non-invasive and real time analysis of bacterial infections in a vertebrate host. Plenty of common pathogens can be examined using zebrafish model: Streptococcus iniae, Vibrio anguillarum or Listeria monocytogenes. The steps are taken to use the zebrafish also in fungal research, especially that dealing with Candida albicans and Cryptococcus neoformans. Although, the zebrafish is used commonly as an animal model to study diseases caused by external agents, it is also useful in studies of metabolic

  13. Perlecan domain V therapy for stroke: a beacon of hope?

    Science.gov (United States)

    Bix, Gregory J

    2013-03-20

    The sad reality is that in the year 2012, people are still dying or suffering from the extreme morbidity of ischemic stroke. This tragedy is only compounded by the graveyard full of once promising new therapies. While it is indeed true that the overall mortality from stroke has declined in the United States, perhaps due to increased awareness of stroke symptoms by both the lay public and physicians, it is clear that better therapies are needed. In this regard, progress has been tremendously slowed by the simple fact that experimental models of stroke and the animals that they typically employ, rats and mice, do not adequately represent human stroke. Furthermore, the neuroprotective therapeutic approach, in which potential treatments are administered with the hope of preventing the spread of dying neurons that accompanies a stroke, typically fail for a number of reasons such as there is simply more brain matter to protect in a human than there is in a rodent! For this reason, there has been somewhat of a shift in stroke research away from neuroprotection and toward a neurorepair approach. This too may be problematic in that agents that might foster brain repair could be acutely deleterious or neurotoxic and vice versa, making the timing of treatment administration after stroke critical. Therefore, in our efforts to discover a new stroke therapy, we decided to focus on identifying brain repair elements that were (1) endogenously and actively generated in response to stroke in both human and experimental animal brains, (2) present acutely and chronically after ischemic stroke, suggesting that they could have a role in acute neuroprotection and chronic neurorepair, and (3) able to be administered peripherally and reach the site of stroke brain injury. In this review, I will discuss the evidence that suggests that perlecan domain V may be just that substance, a potential beacon of hope for stroke patients.

  14. Using Computational and Mechanical Models to Study Animal Locomotion

    Science.gov (United States)

    Miller, Laura A.; Goldman, Daniel I.; Hedrick, Tyson L.; Tytell, Eric D.; Wang, Z. Jane; Yen, Jeannette; Alben, Silas

    2012-01-01

    Recent advances in computational methods have made realistic large-scale simulations of animal locomotion possible. This has resulted in numerous mathematical and computational studies of animal movement through fluids and over substrates with the purpose of better understanding organisms’ performance and improving the design of vehicles moving through air and water and on land. This work has also motivated the development of improved numerical methods and modeling techniques for animal locomotion that is characterized by the interactions of fluids, substrates, and structures. Despite the large body of recent work in this area, the application of mathematical and numerical methods to improve our understanding of organisms in the context of their environment and physiology has remained relatively unexplored. Nature has evolved a wide variety of fascinating mechanisms of locomotion that exploit the properties of complex materials and fluids, but only recently are the mathematical, computational, and robotic tools available to rigorously compare the relative advantages and disadvantages of different methods of locomotion in variable environments. Similarly, advances in computational physiology have only recently allowed investigators to explore how changes at the molecular, cellular, and tissue levels might lead to changes in performance at the organismal level. In this article, we highlight recent examples of how computational, mathematical, and experimental tools can be combined to ultimately answer the questions posed in one of the grand challenges in organismal biology: “Integrating living and physical systems.” PMID:22988026

  15. Prebiotic effect of Agave fourcroydes fructans: an animal model.

    Science.gov (United States)

    García-Curbelo, Yanelys; Bocourt, Ramón; Savón, Lourdes L; García-Vieyra, Maria Isabel; López, Mercedes G

    2015-09-01

    The use of prebiotics such as fructans has increased in human and animal nutrition because of their productive performance and health benefits. Agave fourcroydes has shown high concentrations of fructans in their stems; however, there is no information on new products derived from this plant that might enhance its added value. Therefore, we evaluated the prebiotic effect of Agave fourcroydes fructans in an animal model. Male mice (C57BL/6J) were fed on parallel form with a standard diet or diets supplemented with 10% of fructans from Cichorium intybus (Raftilose P95) and Agave fourcroydes from Cuba for 35 days. The body weight, food intake, blood glucose, triglycerides and cholesterol, gastrointestinal organ weights, fermentation indicators in cecal and colon contents and mineral content in femurs were determined. The body weight and food intake of mice were not significantly modified by any treatment. However, serum glucose, cholesterol and triglycerides decreased (P Agave fourcroydes in the mice diet induced a prebiotic response, similar to or greater than the commercial product (Raftilose P95) and this constitutes a promising alternative with potential use not only in animal but also in human diets.

  16. Using computational and mechanical models to study animal locomotion.

    Science.gov (United States)

    Miller, Laura A; Goldman, Daniel I; Hedrick, Tyson L; Tytell, Eric D; Wang, Z Jane; Yen, Jeannette; Alben, Silas

    2012-11-01

    Recent advances in computational methods have made realistic large-scale simulations of animal locomotion possible. This has resulted in numerous mathematical and computational studies of animal movement through fluids and over substrates with the purpose of better understanding organisms' performance and improving the design of vehicles moving through air and water and on land. This work has also motivated the development of improved numerical methods and modeling techniques for animal locomotion that is characterized by the interactions of fluids, substrates, and structures. Despite the large body of recent work in this area, the application of mathematical and numerical methods to improve our understanding of organisms in the context of their environment and physiology has remained relatively unexplored. Nature has evolved a wide variety of fascinating mechanisms of locomotion that exploit the properties of complex materials and fluids, but only recently are the mathematical, computational, and robotic tools available to rigorously compare the relative advantages and disadvantages of different methods of locomotion in variable environments. Similarly, advances in computational physiology have only recently allowed investigators to explore how changes at the molecular, cellular, and tissue levels might lead to changes in performance at the organismal level. In this article, we highlight recent examples of how computational, mathematical, and experimental tools can be combined to ultimately answer the questions posed in one of the grand challenges in organismal biology: "Integrating living and physical systems."

  17. Fibroblast Growth Factor Type 1 (FGF1)-Overexpressed Adipose-Derived Mesenchaymal Stem Cells (AD-MSCFGF1) Induce Neuroprotection and Functional Recovery in a Rat Stroke Model.

    Science.gov (United States)

    Ghazavi, Hamed; Hoseini, Seyed Javad; Ebrahimzadeh-Bideskan, Alireza; Mashkani, Baratali; Mehri, Soghra; Ghorbani, Ahmad; Sadri, Kayvan; Mahdipour, Elahe; Ghasemi, Faezeh; Forouzanfar, Fatemeh; Hoseini, Azar; Pasdar, Ali Reza; Sadeghnia, Hamid Reza; Ghayour-Mobarhan, Majid

    2017-10-01

    Stroke, as the second most common cause of death, imposes a great financial burden on both the individual and society. Mesenchymal stem cells from rodents have demonstrated efficacy in experimental animal models of stroke due to enhanced neurological recovery. Since FGF1 (fibroblast growth factor 1) displays neuroprotective properties, for the first time, we investigated the effect of acute intravenous administration of FGF1 gene transfected adipose-derived mesenchymal stem cell (AD-MSC FGF1 ) on transient experimental ischemic stroke in rats. Stroke induction was made by transient middle cerebral artery occlusion (tMCAO). 2 × 10 6  AD-MSC FGF1 was administrated intravenously 30 min after carotid reperfusion. The ability of technetium 99m -hexamethyl propylene amine oxime ( 99m Tc-HMPAO)-labeled AD-MSC FGF1 to enter into ischemic brain was evaluated 2 h post injection. 24 h post operation, the neurological recovery (rotarod and Roger's tests), the infarct volume (2, 3, 5-triphenyltetrazolium chloride, TTC assay), apoptosis rate (TUNEL assay), and the expression of FGF1 protein (western blotting) in the ischemic hemisphere were assessed. The 99m Tc-HMPAO-labeled AD-MSC FGF1 could enter into the ischemic brain. Ischemic hemisphere activity was significantly higher than that observed in the contralateral hemisphere (p = 0.002). The administration of AD-MSC FGF1 resulted in significant improvement of neurological function tests and increased density of FGF1 protein in the peri-infarct area, while the infarct volume and the apoptotic index were significantly decreased, in comparison to the other treated groups. In conclusion, acute intravenous administration of AD-MSC FGF1 can be a novel and promising candidate approach for the treatment of ischemic stroke.

  18. Animal model for endoscopic neurosurgical training: technical note.

    Science.gov (United States)

    Fernandez-Miranda, J C; Barges-Coll, J; Prevedello, D M; Engh, J; Snyderman, C; Carrau, R; Gardner, P A; Kassam, A B

    2010-10-01

    The learning curve for endonasal endoscopic and neuroendoscopic port surgery is long and often associated with an increase in complication rates as surgeons gain experience. We present an animal model for laboratory training aiming to encourage the young generation of neurosurgeons to pursue proficiency in endoscopic neurosurgical techniques. 20 Wistar rats were used as models. The animals were introduced into a physical trainer with multiple ports to carry out fully endoscopic microsurgical procedures. The vertical and horizontal dimensions of the paired ports (simulated nostrils) were: 35×20 mm, 35×15 mm, 25×15 mm, and 25×10 mm. 2 additional single 11.5 mm endoscopic ports were added. Surgical depth varied as desired between 8 and 15 cm. The cervical and abdominal regions were the focus of the endoscopic microsurgical exercises. The different endoscopic neurosurgical techniques were effectively trained at the millimetric dimension. Levels of progressive surgical difficulty depending upon the endoneurosurgical skills set needed for a particular surgical exercise were distinguished. LEVEL 1 is soft-tissue microdissection (exposure of cervical muscular plane and retroperitoneal space); LEVEL 2 is soft-tissue-vascular and vascular-capsule microdissection (aorto-cava exposure, carotid sheath opening, external jugular vein isolation); LEVEL 3 is artery-nerve microdissection (carotid-vagal separation); LEVEL 4 is artery-vein microdissection (aorto-cava separation); LEVEL 5 is vascular repair and microsuturing (aortic rupture), which verified the lack of current proper instrumentation. The animal training model presented here has the potential to shorten the length of the learning curve in endonasal endoscopic and neuroendoscopic port surgery and reduce the incidence of training-related surgical complications. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Utility of Small Animal Models of Developmental Programming.

    Science.gov (United States)

    Reynolds, Clare M; Vickers, Mark H

    2018-01-01

    Any effective strategy to tackle the global obesity and rising noncommunicable disease epidemic requires an in-depth understanding of the mechanisms that underlie these conditions that manifest as a consequence of complex gene-environment interactions. In this context, it is now well established that alterations in the early life environment, including suboptimal nutrition, can result in an increased risk for a range of metabolic, cardiovascular, and behavioral disorders in later life, a process preferentially termed developmental programming. To date, most of the mechanistic knowledge around the processes underpinning development programming has been derived from preclinical research performed mostly, but not exclusively, in laboratory mouse and rat strains. This review will cover the utility of small animal models in developmental programming, the limitations of such models, and potential future directions that are required to fully maximize information derived from preclinical models in order to effectively translate to clinical use.

  20. Thymoma related myasthenia gravis in humans and potential animal models.

    Science.gov (United States)

    Marx, Alexander; Porubsky, Stefan; Belharazem, Djeda; Saruhan-Direskeneli, Güher; Schalke, Berthold; Ströbel, Philipp; Weis, Cleo-Aron

    2015-08-01

    Thymoma-associated Myasthenia gravis (TAMG) is one of the anti-acetylcholine receptor MG (AChR-MG) subtypes. The clinico-pathological features of TAMG and its pathogenesis are described here in comparison with pathogenetic models suggested for the more common non-thymoma AChR-MG subtypes, early onset MG and late onset MG. Emphasis is put on the role of abnormal intratumorous T cell selection and activation, lack of intratumorous myoid cells and regulatory T cells as well as deficient expression of the autoimmune regulator (AIRE) by neoplastic thymic epithelial cells. We review spontaneous and genetically engineered thymoma models in a spectrum of animals and the extensive clinical and immunological overlap between canine, feline and human TAMG. Finally, limitations and perspectives of the transplantation of human and murine thymoma tissue into nude mice, as potential models for TAMG, are addressed. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Validity and Variability of Animal Models Used in Dentistry

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Saghiri

    2015-01-01

    Full Text Available Background: Animal models have contributed to dental literature for several decades. The major aim of this review was to outline tooth development stages in mice, and attempt to addressing potential strain differences. A literature review was performed using electronic and hand-searching methods for the animal models in dentistry with special emphasis on mice and dentistry. Root canal development in both C57BL/6 and BALB/c strains were investigated. There are a number of published reports regarding the morphogenesis and molecular reaction and maturation stages of mice molars. We observed some similarity between the mice and human odontegeneis as primary factor for tooth development. Although mice may present some technical challenges, including the small size of the mouse molars, they have similar stages as humans for molar development, and can be used to monitor the effects of various biomaterials, regeneration, and remodeling. Thus, mice provide an ideal alternative model to study developmental and regenerative processes in dentistry.

  2. Steroid-associated osteonecrosis animal model in rats

    Directory of Open Access Journals (Sweden)

    Li-Zhen Zheng

    2018-04-01

    Full Text Available Summary: Objective: Established preclinical disease models are essential for not only studying aetiology and/or pathophysiology of the relevant diseases but more importantly also for testing prevention and/or treatment concept(s. The present study proposed and established a detailed induction and assessment protocol for a unique and cost-effective preclinical steroid-associated osteonecrosis (SAON in rats with pulsed injections of lipopolysaccharide (LPS and methylprednisolone (MPS. Methods: Sixteen 24-week-old male Sprague–Dawley rats were used to induce SAON by one intravenous injection of LPS (0.2 mg/kg and three intraperitoneal injections of MPS (100 mg/kg with a time interval of 24 hour, and then, MPS (40 mg/kg was intraperitoneally injected three times a week from week 2 until sacrifice. Additional 12 rats were used as normal controls. Two and six weeks after induction, animals were scanned by metabolic dual energy X-ray absorptiometry for evaluation of tissue composition; serum was collected for bone turnover markers, Microfil perfusion was performed for angiography, the liver was collected for histopathology and bilateral femora and bilateral tibiae were collected for histological examination. Results: Three rats died after LPS injection, i.e., with 15.8% (3/19 mortality. Histological evaluation showed 100% incidence of SAON at week 2. Dual energy X-ray absorptiometry showed significantly higher fat percent and lower lean mass in SAON group at week 6. Micro-computed tomography (Micro-CT showed significant bone degradation at proximal tibia 6 weeks after SAON induction. Angiography illustrated significantly less blood vessels in the proximal tibia and significantly more leakage particles in the distal tibia 2 weeks after SAON induction. Serum amino-terminal propeptide of type I collagen and osteocalcin were significantly lower at both 2 and 6 weeks after SAON induction, and serum carboxy-terminal telopeptide was significantly

  3. Imaging of Small Animal Peripheral Artery Disease Models: Recent Advancements and Translational Potential

    Directory of Open Access Journals (Sweden)

    Jenny B. Lin

    2015-05-01

    Full Text Available Peripheral artery disease (PAD is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead to rupture, while ischemic atherosclerosis reduces blood flow, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely because these disorders are commonly undiagnosed or misdiagnosed. Active areas of research are focused on detecting and characterizing deleterious arterial changes at early stages using non-invasive imaging strategies, such as ultrasound, as well as emerging technologies like photoacoustic imaging. Earlier disease detection and characterization could improve interventional strategies, leading to better prognosis in PAD patients. While rodents are being used to investigate PAD pathophysiology, imaging of these animal models has been underutilized. This review focuses on structural and molecular information and disease progression revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular disease models in mice, rats, and rabbits. Effective translation to humans involves better understanding of underlying PAD pathophysiology to develop novel therapeutics and apply non-invasive imaging techniques in the clinic.

  4. Fuzzy classification of phantom parent groups in an animal model

    Directory of Open Access Journals (Sweden)

    Fikse Freddy

    2009-09-01

    Full Text Available Abstract Background Genetic evaluation models often include genetic groups to account for unequal genetic level of animals with unknown parentage. The definition of phantom parent groups usually includes a time component (e.g. years. Combining several time periods to ensure sufficiently large groups may create problems since all phantom parents in a group are considered contemporaries. Methods To avoid the downside of such distinct classification, a fuzzy logic approach is suggested. A phantom parent can be assigned to several genetic groups, with proportions between zero and one that sum to one. Rules were presented for assigning coefficients to the inverse of the relationship matrix for fuzzy-classified genetic groups. This approach was illustrated with simulated data from ten generations of mass selection. Observations and pedigree records were randomly deleted. Phantom parent groups were defined on the basis of gender and generation number. In one scenario, uncertainty about generation of birth was simulated for some animals with unknown parents. In the distinct classification, one of the two possible generations of birth was randomly chosen to assign phantom parents to genetic groups for animals with simulated uncertainty, whereas the phantom parents were assigned to both possible genetic groups in the fuzzy classification. Results The empirical prediction error variance (PEV was somewhat lower for fuzzy-classified genetic groups. The ranking of animals with unknown parents was more correct and less variable across replicates in comparison with distinct genetic groups. In another scenario, each phantom parent was assigned to three groups, one pertaining to its gender, and two pertaining to the first and last generation, with proportion depending on the (true generation of birth. Due to the lower number of groups, the empirical PEV of breeding values was smaller when genetic groups were fuzzy-classified. Conclusion Fuzzy

  5. Stem cell-like dog placenta cells afford neuroprotection against ischemic stroke model via heat shock protein upregulation.

    Directory of Open Access Journals (Sweden)

    Seongjin Yu

    Full Text Available In this study, we investigated the dog placenta as a viable source of stem cells for stroke therapy. Immunocytochemical evaluation of phenotypic markers of dog placenta cells (DPCs cultured in proliferation and differentiation medium revealed that DPCs expressed both stem cell and neural cell markers, respectively. Co-culture with DPCs afforded neuroprotection of rat primary neural cells in a dose-dependent manner against oxygen-glucose deprivation. Subsequent in vivo experiments showed that transplantation of DPCs, in particular intravenous and intracerebral cell delivery, produced significant behavioral recovery and reduced histological deficits in ischemic stroke animals compared to those that received intra-arterial delivery of DPCs or control stroke animals. Furthermore, both in vitro and in vivo studies implicated elevated expression of heat shock protein 27 (Hsp27 as a potential mechanism of action underlying the observed therapeutic benefits of DPCs in stroke. This study supports the use of stem cells for stroke therapy and implicates a key role of Hsp27 signaling pathway in neuroprotection.

  6. Teleneurology in stroke management: costs of service in different organizational models.

    Science.gov (United States)

    Handschu, René; Scibor, Mateusz; Nückel, Martin; Asshoff, Dirk; Willaczek, Barbara; Erbguth, Frank; Schwab, Stefan; Daumann, Frank

    2014-10-01

    Telemedicine is in increasing use in clinical neuroscience such as acute stroke care, especially by applying remote audiovisual communication for patient evaluation. However, telephone consultation was also used linking stroke centres to smaller hospitals. We compared costs of telestroke services using audiovisual and telephone communication in different organizational models. Within a small network in Northern Bavaria video-based teleconsultation (VTC) and telephone advice (TA) was provided for evaluation of acute stroke patients on a weekly rotation. The costs of the admissions process with or without one of both methods of telemedicine were calculated and compared from the perspective of the spoke hospital. Different levels of service and network size were modelled and costs of transfers as well as loss of revenues were calculated. Yearly total labour costs were 415,000 € for an on-site service VTC-service compared to 61,000 € in an on-call service. Additional costs for one teleconsultation were 109.55 € in VTC and 49.82 € in TA (VTC/TA ratio 2.2). The ratio decreased to 0.8 when accounting for costs of transfer and loss of reimbursement for all patients transferred as transfer of patients to the stroke centre was more frequent after TA (9.1 vs. 14.9%full-time on-site ser). Costs of one QALY gained by using VTC instead of TA ranged from 115.00 € to 515.86 € depending on the different models. In the first view TA looks like the less expensive method as it is easy to access and works without additional costs. When accounting for all disadvantages TA becomes slightly more expensive. In telestroke care VTC should be recommended as the method of choice also from an economic perspective.

  7. Shigella vaccine development: prospective animal models and current status.

    Science.gov (United States)

    Kim, Yeon-Jeong; Yeo, Sang-Gu; Park, Jae-Hak; Ko, Hyun-Jeong

    2013-01-01

    Shigella was first discovered in 1897 and is a major causative agent of dysenteric diarrhea. The number of affected patients has decreased globally because of improved sanitary conditions; however, Shigella still causes serious problems in many subjects, including young children and the elderly, especially in developing countries. Although antibiotics may be effective, a vaccine would be the most powerful solution to combat shigellosis because of the emergence of drug-resistant strains. However, the development of a vaccine is hampered by several problems. First, there is no suitable animal model that can replace human-based studies for the investigation of the in vivo mechanisms of Shigella vaccines. Mouse, guinea pig, rat, rabbit, and nonhuman primates could be used as models for shigellosis, but they do not represent human shigellosis and each has its own weaknesses. However, a recent murine model based on peritoneal infection with virulent S. flexneri 2a is promising. Moreover, although the inflammatory responses and mechanisms such as pathogenassociated molecular patterns and danger-associated molecular patterns have been studied, the pathology and immunology of Shigella are still not clearly defined. Despite these obstacles, many vaccine candidates have been developed, including live attenuated, killed whole cells, conjugated, and subunit vaccines. The development of Shigella vaccines also demands considerations of the cost, routes of administration, ease of storage (stability), cross-reactivity, safety, and immunogenicity. The main aim of this review is to provide a detailed introduction to the many promising vaccine candidates and animal models currently available, including the newly developed mouse model.

  8. The animal model determines the results of Aeromonas virulence factors

    Directory of Open Access Journals (Sweden)

    Alejandro Romero

    2016-10-01

    Full Text Available The selection of an experimental animal model is of great importance in the study of bacterial virulence factors. Here, a bath infection of zebrafish larvae is proposed as an alternative model to study the virulence factors of A. hydrophila. Intraperitoneal infections in mice and trout were compared with bath infections in zebrafish larvae using specific mutants. The great advantage of this model is that bath immersion mimics the natural route of infection, and injury to the tail also provides a natural portal of entry for the bacteria. The implication of T3SS in the virulence of A. hydrophila was analysed using the AH-1::aopB mutant. This mutant was less virulent than the wild-type strain when inoculated into zebrafish larvae, as described in other vertebrates. However, the zebrafish model exhibited slight differences in mortality kinetics only observed using invertebrate models. Infections using the mutant AH-1∆vapA lacking the gene coding for the surface S-layer suggested that this protein was not totally necessary to the bacteria once it was inside the host, but it contributed to the inflammatory response. Only when healthy zebrafish larvae were infected did the mutant produce less mortality than the wild type. Variations between models were evidenced using the AH-1∆rmlB, which lacks the O-antigen lipopolysaccharide (LPS, and the AH-1∆wahD, which lacks the O-antigen LPS and part of the LPS outer-core. Both mutants showed decreased mortality in all of the animal models, but the differences between them were only observed in injured zebrafish larvae, suggesting that residues from the LPS outer core must be important for virulence. The greatest differences were observed using the AH-1ΔFlaB-J (lacking polar flagella and unable to swim and the AH-1::motX (non-motile but producing flagella. They were as pathogenic as the wild-type strain when injected into mice and trout, but no mortalities were registered in zebrafish larvae. This study

  9. Computer-aided pulmonary image analysis in small animal models

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ziyue; Mansoor, Awais; Mollura, Daniel J. [Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892 (United States); Bagci, Ulas, E-mail: ulasbagci@gmail.com [Center for Research in Computer Vision (CRCV), University of Central Florida (UCF), Orlando, Florida 32816 (United States); Kramer-Marek, Gabriela [The Institute of Cancer Research, London SW7 3RP (United Kingdom); Luna, Brian [Microfluidic Laboratory Automation, University of California-Irvine, Irvine, California 92697-2715 (United States); Kubler, Andre [Department of Medicine, Imperial College London, London SW7 2AZ (United Kingdom); Dey, Bappaditya; Jain, Sanjay [Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 (United States); Foster, Brent [Department of Biomedical Engineering, University of California-Davis, Davis, California 95817 (United States); Papadakis, Georgios Z. [Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892 (United States); Camp, Jeremy V. [Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202 (United States); Jonsson, Colleen B. [National Institute for Mathematical and Biological Synthesis, University of Tennessee, Knoxville, Tennessee 37996 (United States); Bishai, William R. [Howard Hughes Medical Institute, Chevy Chase, Maryland 20815 and Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 (United States); Udupa, Jayaram K. [Medical Image Processing Group, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States)

    2015-07-15

    Purpose: To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models. Methods: The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors’ system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next. The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters. Results: 133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT’09 data set. Conclusions: The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.

  10. Neuro-immune interactions of neural stem cell transplants: from animal disease models to human trials.

    Science.gov (United States)

    Giusto, Elena; Donegà, Matteo; Cossetti, Chiara; Pluchino, Stefano

    2014-10-01

    Stem cell technology is a promising branch of regenerative medicine that is aimed at developing new approaches for the treatment of severely debilitating human diseases, including those affecting the central nervous system (CNS). Despite the increasing understanding of the mechanisms governing their biology, the application of stem cell therapeutics remains challenging. The initial idea that stem cell transplants work in vivo via the replacement of endogenous cells lost or damaged owing to disease has been challenged by accumulating evidence of their therapeutic plasticity. This new concept covers the remarkable immune regulatory and tissue trophic effects that transplanted stem cells exert at the level of the neural microenvironment to promote tissue healing via combination of immune modulatory and tissue protective actions, while retaining predominantly undifferentiated features. Among a number of promising candidate stem cell sources, neural stem/precursor cells (NPCs) are under extensive investigation with regard to their therapeutic plasticity after transplantation. The significant impact in vivo of experimental NPC therapies in animal models of inflammatory CNS diseases has raised great expectations that these stem cells, or the manipulation of the mechanisms behind their therapeutic impact, could soon be translated to human studies. This review aims to provide an update on the most recent evidence of therapeutically-relevant neuro-immune interactions following NPC transplants in animal models of multiple sclerosis, cerebral stroke and traumas of the spinal cord, and consideration of the forthcoming challenges related to the early translation of some of these exciting experimental outcomes into clinical medicines. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Tissue and Animal Models of Sudden Cardiac Death

    Science.gov (United States)

    Sallam, Karim; Li, Yingxin; Sager, Philip T.; Houser, Steven R.; Wu, Joseph C.

    2015-01-01

    Sudden Cardiac Death (SCD) is a common cause of death in patients with structural heart disease, genetic mutations or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with SCD. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell derived Cardiomyocytes (iPSC-CMs) resemble, but are not identical, to adult human cardiomyocytes, and provide a new platform for studying arrhythmic disorders leading to SCD. A variety of platforms exist to phenotype cellular models including conventional and automated patch clamp, multi-electrode array, and computational modeling. iPSC-CMs have been used to study Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy and other hereditary cardiac disorders. Although iPSC-CMs are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of SCD. PMID:26044252

  12. Animal Models of Schizophrenia with a Focus on Models Targeting NMDA Receptors

    Czech Academy of Sciences Publication Activity Database

    Svojanovská, Markéta; Stuchlík, Aleš

    2015-01-01

    Roč. 4, č. 1 (2015), s. 3-18 ISSN 1805-7225 R&D Projects: GA MZd(CZ) NT13386 Institutional support: RVO:67985823 Keywords : schizophrenia * animal models * pharmacological models * genetic models * neurodevelopmental models * preclinical studies Subject RIV: FH - Neurology

  13. Old and new synthetic cannabinoids: lessons from animal models.

    Science.gov (United States)

    Zanda, Mary Tresa; Fattore, Liana

    2018-02-01

    Synthetic cannabinoids have long been studied for their therapeutic potentials. However, during the last decade, new generations of synthetic cannabinoid agonists appeared on the drug market. These new psychoactive substances are currently sold as 'marijuana-like' products as they claim to mimic the effects of the psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC). Yet, their effects are more intense and potent than THC, typically last longer and are often associated to serious psychiatric consequences. Animal models of drug addiction are frequently used in preclinical research to assess the abuse potential of new compounds, evaluate drug positive reinforcing effects and analyze drug-induced behaviors. Some of these protocols have been used recently to study the newly synthesized cannabinoid agonists and have started elucidating their pharmacology and actions in the brain. The aim of this review is to summarize the major findings reported by animal studies that tested synthetic cannabinoids of first, second, and third generation by using self-administration and reinstatement models, drug discrimination and conditioned place preference procedures. Altogether, behavioral studies clearly indicate that synthetic cannabinoids possess abuse liability, are likely to activate the brain reward circuit and induce positive subjective and reinforcing effects.

  14. Cytokine networks in animal models of colitis-associated cancer.

    Science.gov (United States)

    Antoniou, Efstathios; Margonis, Georgios Antonios; Angelou, Anastasios; Zografos, George C; Pikoulis, Emmanouil

    2015-01-01

    It is well-known that inflammatory bowel disease (IBD) poses an increased, yet not definitely estimated, risk of colitis-associated colon cancer (CAC), which is considered a more aggressive and distinct in both genetic and molecular levels clinical entity compared to sporadic colorectal cancer (CRC). The present review discusses the cytokine networks involved in CAC-based translational findings from suitable animal models of the disease. Moreover, we summarize the most prominent data concerning the role of Th1, Th2, Th17 and anti-inflammatory cytokines in the pathogenesis of CAC. Last, we briefly address the controversies between basic science findings in IBD and CAC and suggest further directions regarding research on cytokines. This review should serve as a primer for clinicians and surgeons to understand the rapidly evolving field of cytokines in the context of CAC. The MEDLINE database was thoroughly searched using the keywords: cytokines, colitis-associated cancer, animal models, carcinogenesis. Additional articles were gathered and evaluated. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  15. Experimental animal data and modeling of late somatic effects

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1988-01-01

    This section is restricted to radiation-induced life shortening and cancer and mainly to studies with external radiation. The emphasis will be on the experimental data that are available and the experimental systems that could provide the type of data with which to either formulate or test models. Genetic effects which are of concern are not discussed in this section. Experimental animal radiation studies fall into those that establish general principles and those that demonstrate mechanisms. General principles include the influence of dose, radiation quality, dose rate, fractionation, protraction and such biological factors as age and gender. The influence of these factors are considered as general principles because they are independent, at least qualitatively, of the species studied. For example, if an increase in the LET of the radiation causes an increased effectiveness in cancer induction in a mouse a comparable increase in effectiveness can be expected in humans. Thus, models, whether empirical or mechanistic, formulated from experimental animal data should be generally applicable

  16. Minimally invasive resynchronization pacemaker: a pediatric animal model.

    Science.gov (United States)

    Jordan, Christopher P; Wu, Kyle; Costello, John P; Ishibashi, Nobuyuki; Krieger, Axel; Kane, Timothy D; Kim, Peter; Berul, Charles I

    2013-12-01

    We developed a minimally invasive epicardial pacemaker implantation method for infants and congenital heart disease patients for whom a transvenous approach is contraindicated. The piglet is an ideal model for technical development. In 5 piglets we introduced a needle through subxiphoid approach under thoracoscopic guidance, inserting a wire into the pericardial space. Pacing leads were affixed to the left ventricular free wall and left atrial appendage. After verifying functionality with atrial and ventricular pacing and sensing, animals were euthanized. Pacemaker monitoring occurred daily for 4 days in the fifth animal. Through minimally invasive pericardial access, we directly visualized and fixated pacing leads to the left ventricle and left atrial appendage, successfully pacing atrium and ventricle. Epicardial structures were visualized. One piglet had contralateral pneumothorax, which resolved with needle decompression. No other adverse events occurred. Minimally invasive epicardial pacemaker implantation in an infant model is feasible and effective. This innovation may be of value for pacing and resynchronization in infants and congenital heart disease patients. Survival studies with permanent generator implantation are under way. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Ocular Manifestations of Alzheimer’s Disease in Animal Models

    Directory of Open Access Journals (Sweden)

    Miles Parnell

    2012-01-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia, and the pathological changes of senile plaques (SPs and neurofibrillary tangles (NFTs in AD brains are well described. Clinically, a diagnosis remains a postmortem one, hampering both accurate and early diagnosis as well as research into potential new treatments. Visual deficits have long been noted in AD patients, and it is becoming increasingly apparent that histopathological changes already noted in the brain also occur in an extension of the brain; the retina. Due to the optically transparent nature of the eye, it is possible to image the retina at a cellular level noninvasively and thus potentially allow an earlier diagnosis as well as a way of monitoring progression and treatment effects. Transgenic animal models expressing amyloid precursor protein (APP presenilin (PS and tau mutations have been used successfully to recapitulate the pathological findings of AD in the brain. This paper will cover the ocular abnormalities that have been detected in these transgenic AD animal models.

  18. Experimental animal data and modeling of late somatic effects

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1988-01-01

    This section is restricted to radiation-induced life shortening and cancer and mainly to studies with external radiation. The emphasis will be on the experimental data that are available and the experimental systems that could provide the type of data with which to either formulate or test models. Genetic effects which are of concern are not discussed in this section. Experimental animal radiation studies fall into those that establish general principles and those that demonstrate mechanisms. General principles include the influence of dose, radiation quality, dose rate, fractionation, protraction and such biological factors as age and gender. The influence of these factors are considered as general principles because they are independent, at least qualitatively, of the species studied. For example, if an increase in the LET of the radiation causes an increased effectiveness in cancer induction in a mouse a comparable increase in effectiveness can be expected in humans. Thus, models, whether empirical or mechanistic, formulated from experimental animal data should be generally applicable.

  19. Genetic Engineering of Dystroglycan in Animal Models of Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Francesca Sciandra

    2015-01-01

    Full Text Available In skeletal muscle, dystroglycan (DG is the central component of the dystrophin-glycoprotein complex (DGC, a multimeric protein complex that ensures a strong mechanical link between the extracellular matrix and the cytoskeleton. Several muscular dystrophies arise from mutations hitting most of the components of the DGC. Mutations within the DG gene (DAG1 have been recently associated with two forms of muscular dystrophy, one displaying a milder and one a more severe phenotype. This review focuses specifically on the animal (murine and others model systems that have been developed with the aim of directly engineering DAG1 in order to study the DG function in skeletal muscle as well as in other tissues. In the last years, conditional animal models overcoming the embryonic lethality of the DG knock-out in mouse have been generated and helped clarifying the crucial role of DG in skeletal muscle, while an increasing number of studies on knock-in mice are aimed at understanding the contribution of single amino acids to the stability of DG and to the possible development of muscular dystrophy.

  20. Dissecting OCD Circuits: From Animal Models to Targeted Treatments

    Science.gov (United States)

    Ahmari, Susanne E.; Dougherty, Darin D.

    2015-01-01

    Obsessive Compulsive Disorder (OCD) is a chronic, severe mental illness with up to 2–3% prevalence worldwide, which has been classified as one of the world’s 10 leading causes of illness-related disability according to the World Health Organization, largely because of the chronic nature of disabling symptoms 1. Despite the severity and high prevalence of this chronic and disabling disorder, there is still relatively limited understanding of its pathophysiology. However, this is now rapidly changing due to development of powerful technologies that can be used to dissect the neural circuits underlying pathologic behaviors. In this article, we describe recent technical advances that have allowed neuroscientists to start identifying the circuits underlying complex repetitive behaviors using animal model systems. In addition, we review current surgical and stimulation-based treatments for OCD that target circuit dysfunction. Finally, we discuss how findings from animal models may be applied in the clinical arena to help inform and refine targeted brain stimulation-based treatment approaches. PMID:25952989

  1. An intermediate animal model of spinal cord stimulation

    Directory of Open Access Journals (Sweden)

    Thomas Guiho

    2016-06-01

    Full Text Available Spinal cord injuries (SCI result in the loss of movement and sensory feedback as well as organs dysfunctions. For example, nearly all SCI subjects loose their bladder control and are prone to kidney failure if they do not proceed to intermittent (self- catheterization. Electrical stimulation of the sacral spinal roots with an implantable neuroprosthesis is a promising approach, with commercialized products, to restore continence and control micturition. However, many persons do not ask for this intervention since a surgical deafferentation is needed and the loss of sensory functions and reflexes become serious side effects of this procedure. Recent results renewed interest in spinal cord stimulation. Stimulation of existing pre-cabled neural networks involved in physiological processes regulation is suspected to enable synergic recruitment of spinal fibers. The development of direct spinal stimulation strategies aiming at bladder and bowel functions restoration would therefore appear as a credible alternative to existent solutions. However, a lack of suitable large animal model complicates these kinds of studies. In this article, we propose a new animal model of spinal stimulation -pig- and will briefly introduce results from one first acute experimental validation session.

  2. Behavior of lyophilized biological valves in a chronic animal model.

    Science.gov (United States)

    Maizato, Marina J S; Taniguchi, Fabio P; Ambar, Rafael F; Pitombo, Ronaldo N M; Leirner, Adolfo A; Cestari, Idágene A; Stolf, Noedir A G

    2013-11-01

    Glutaraldehyde is used in order to improve the mechanical and immunogenic properties of biological tissues, such as bovine pericardium membranes, used to manufacture heart valve bioprostheses. Lyophilization, also known as freeze-drying, preserves biological material without damage by freezing the water content and removing ice by sublimation. Through this process, dehydrated products of high quality may be obtained; also, the material may be easily handled. The lyophilization process reduces aldehyde residues in biological tissue previously treated with glutaraldehyde, thus promoting reduction of cytotoxicity, increasing resistance to inflammation, and possibly decreasing the potential for tissue calcification. The objective of this study was to chronically evaluate the calcification of bovine pericardium heart valve prostheses, previously lyophilized or not, in an animal model. Six-month-old sheep received implants of lyophilized and unlyophilized heart valve prostheses in the pulmonary position with right bypass. The study followed 16 animals for a period of 90 days. Right ventricle-pulmonary artery (RV/PA) transvalvular pressure gradient was evaluated before and immediately after implantation and before explantation, as were tissue calcium, inflammation intensity, and thrombosis and pannus formation. The t-test was used for statistical analysis. Twelve animals survived to the end of the experiment, but one of the animals in the control group had endocarditis and was excluded from the data. Four animals died early. The mean RV/PA gradient on implantation was 2.0 ± 1.6 mm Hg in the control group and 6.2 ± 4.1 mm Hg in the lyophilized group (P = 0.064). This mean gradient increased at explantation to 7.7 ± 3.9 mm Hg and 8.6 ± 5.8 mm Hg, respectively (P = 0.777). The average calcium content in the tissue leaflets after 3 months was 21.6 ± 39.1 mg Ca(2+)/g dry weight in the control group, compared with an average content of 41.2 ± 46.9 mg Ca(2+)/g dry weight

  3. Comparison of quantitative estimation of intracerebral hemorrhage and infarct volumes after thromboembolism in an embolic stroke model

    DEFF Research Database (Denmark)

    Eriksen, Nina; Rasmussen, Rune Skovgaard; Overgaard, Karsten

    2014-01-01

    BACKGROUND: Strokes have both ischemic and hemorrhagic components, but most studies of experimental stroke only address the ischemic component. This is likely because investigations of hemorrhagic transformation are hindered by the lack of methods based on unbiased principles for volume estimation....... AIMS: We evaluated different methods for estimating the volume of infarcts, hemorrhages, after embolic middle cerebral artery occlusion with or without thrombolysis. METHODS: An experimental thromboembolytic rat model was used in this study. The rats underwent surgery and were placed in two groups...... of measuring both the ischemic and the hemorrhagic components of stroke, two parameters that may be differentially regulated when therapeutic regimens are tested....

  4. Toxin-Induced and Genetic Animal Models of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Shin Hisahara

    2011-01-01

    Full Text Available Parkinson's disease (PD is a common progressive neurodegenerative disorder. The major pathological hallmarks of PD are the selective loss of nigrostriatal dopaminergic neurons and the presence of intraneuronal aggregates termed Lewy bodies (LBs, but the pathophysiological mechanisms are not fully understood. Epidemiologically, environmental neurotoxins such as pesticides are promising candidates for causative factors of PD. Oxidative stress and mitochondrial dysfunction induced by these toxins could contribute to the progression of PD. While most cases of PD are sporadic, specific mutations in genes that cause familial forms of PD have led to provide new insights into its pathogenesis. This paper focuses on animal models of both toxin-induced and genetically determined PD that have provided significant insight for understanding this disease. We also discuss the validity, benefits, and limitations of representative models.

  5. Nicotine addiction: studies about vulnerability, epigenesis and animal models

    Directory of Open Access Journals (Sweden)

    Bernabeu, Ramon

    2013-07-01

    Full Text Available This article is a summary about the current research of nicotine effects on the nervous system and its relationship to the generation of an addictive behavior. Like other drugs of abuse, nicotine activates the reward pathway, which in turn is involved in certain psychiatric diseases. There are individuals who have a high vulnerability to nicotine addiction. This may be due to genetic and epigenetic factors and/or the environment. In this review, we described some epigenetic factors that may be involved in those phenomena. The two animal models most widely used for studying the reinforcing effects of nicotine are: self-administration and conditioning place preference (CPP. Here, we emphasized the CPP, due to its potential application in humans. In addition, we described the locomotor activity model (as a measure of psychostimulant effects to study vulnerability to drugs of abuse

  6. Learning from Animal Models of Obsessive-Compulsive Disorder

    Science.gov (United States)

    Monteiro, Patricia; Feng, Guoping

    2015-01-01

    Obsessive-Compulsive Disorder (OCD) affects 2–3% of the worldwide population and can cause significant distress and disability to its sufferers. Substantial challenges remain in the field of OCD research and therapeutics. Approved interventions only partially alleviate symptoms, with 30–40% of patients being resistant to treatment. Research evidence points towards the involvement of cortico-striato-thalamocortical circuitry (CSTC) although OCD’s etiology is still unknown. This review will focus on the most recent behavior, genetics and neurophysiological findings from animal models of OCD. Based on evidence from these models and parallels with human studies, we discuss the circuit hyperactivity hypothesis for OCD, a potential circuitry dysfunction of action termination, and the involvement of candidate genes. Adding a more biologically-valid framework to OCD will help us define and test new hypotheses and facilitate the development of targeted therapies based on disease-specific mechanisms. PMID:26037910

  7. Modeling of Lightning Strokes Using Two-Peaked Channel-Base Currents

    Directory of Open Access Journals (Sweden)

    V. Javor

    2012-01-01

    Full Text Available Lightning electromagnetic field is obtained by using “engineering” models of lightning return strokes and new channel-base current functions and the results are presented in this paper. Experimentally measured channel-base currents are approximated not only with functions having two-peaked waveshapes but also with the one-peaked function so as usually used in the literature. These functions are simple to be applied in any “engineering” or electromagnetic model as well. For the three “engineering” models: transmission line model (without the peak current decay, transmission line model with linear decay, and transmission line model with exponential decay with height, the comparison of electric and magnetic field components at different distances from the lightning channel-base is presented in the case of a perfectly conducting ground. Different heights of lightning channels are also considered. These results enable analysis of advantages/shortages of the used return stroke models according to the electromagnetic field features to be achieved, as obtained by measurements.

  8. Gastroprotective activity of Zanthoxylum rhoifolium Lam. in animal models.

    Science.gov (United States)

    Freitas, F F B P; Fernandes, H B; Piauilino, C A; Pereira, S S; Carvalho, K I M; Chaves, M H; Soares, P M G; Miura, L M C V; Leite, J R S A; Oliveira, R C M; Oliveira, F A

    2011-09-01

    The stem barks of Zanthoxylum rhoifolium Lam. (Rutaceae), locally known as "mamica de cadela", are popularly used in dyspepsies, stomachic, tonic, antitumoral, antipyretic and are used in treating flatulence and colic. The objective of this study was to evaluate the gastroprotective effect of the ethanolic extract of Zanthoxylum rhoifolium (EEZR) stem barks in acute gastric lesion models, investigating their possible mechanisms. Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The gastroprotective action of EEZR was analyzed in the absolute ethanol, HCl/ethanol and indomethacin-induced gastric lesion models in mice, hypothermic-restraint stress, and ischemia/reperfusion in rats. In the investigation of the gastroprotective mechanisms of EEZR, the participation of the NO-synthase pathway, ATP-sensitive potassium channels (K(ATP)), the levels of the non-protein sulfhydril groups (NP-SH) and the catalase activity using the ethanol-induced gastric mucosa lesion model and the quantification of the gastric mucus and the antisecretory activity through pylorus ligature model in rats were analyzed. The animals did not present any signs of acute toxicity for the EEZR (up to the 4 g/kg dose, po), and it was not possible to calculate the DL(50). EEZR (125-500 mg/kg) exhibited a significant gastroprotective effect in absolute ethanol, HCl/ethanol, hypothermic-restraint stress, and ischemia/reperfusion-induced gastric lesion models. EEZR (250 and 500 mg/kg) exhibited still a gastroprotective activity in the indomethacin-induced ulcer model. Gastroprotection of EEZR was significantly decreased in pre-treated mice with l-NAME or glibenclamide, the respective nitric oxide synthase and K(ATP) channels inhibitors. Our studies revealed that EEZR (500 mg/kg) prevented the decrease of the non-protein sulfhydril groups (NP-SH) and increased the catalase levels in ethanol-treated animals. Furthermore, the extract (500 mg

  9. N-3 polyunsaturated fatty acids in animal models with neuroinflammation: An update.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Hopperton, Kathryn E; Orr, Sarah K; Bazinet, Richard P

    2016-08-15

    Neuroinflammation is a characteristic of a multitude of neurological and psychiatric disorders. Modulating inflammatory pathways offers a potential therapeutic target in these disorders. Omega-3 polyunsaturated fatty acids have anti-inflammatory and pro-resolving properties in the periphery, however, their effect on neuroinflammation is less studied. This review summarizes 61 animal studies that tested the effect of omega-3 polyunsaturated fatty acids on neuroinflammatory outcomes in vivo in various models including stroke, spinal cord injury, aging, Alzheimer's disease, Parkinson's disease, lipopolysaccharide and IL-1β injections, diabetes, neuropathic pain, traumatic brain injury, depression, surgically induced cognitive decline, whole body irradiation, amyotrophic lateral sclerosis, N-methyl-D-aspartate-induced excitotoxicity and lupus. The evidence presented in this review suggests anti-neuroinflammatory properties of omega-3 polyunsaturated fatty acids, however, it is not clear by which mechanism omega-3 polyunsaturated fatty acids exert their effect. Future research should aim to isolate the effect of omega-3 polyunsaturated fatty acids on neuroinflammatory signaling in vivo and elucidate the mechanisms underlying these effects. Copyright © 2016. Published by Elsevier B.V.

  10. Is it acceptable to use animals to model obese humans?

    DEFF Research Database (Denmark)

    Lund, Thomas Bøker; Sørensen, Thorkild I.A.; Olsson, I. Anna S.

    2014-01-01

    for the view that this form of animal use, unlike some other forms of animal-based medical research, cannot be defended. The first argument leans heavily on the notion that people themselves are responsible for developing obesity and so-called 'lifestyle' diseases; the second involves the claim that animal......Animal use in medical research is widely accepted on the basis that it may help to save human lives and improve their quality of life. Recently, however, objections have been made specifically to the use of animals in scientific investigation of human obesity. This paper discusses two arguments...... of animals in obesity research as especially problematic....

  11. Aerodynamic efficiency of flapping flight: analysis of a two-stroke model.

    Science.gov (United States)

    Wang, Z Jane

    2008-01-01

    To seek the simplest efficient flapping wing motions and understand their relation to steady flight, a two-stroke model in the quasi-steady limit was analyzed. It was found that a family of two-stroke flapping motions have aerodynamic efficiency close to, but slightly lower than, the optimal steady flight. These two-stroke motions share two common features: the downstroke is a gliding motion and the upstroke has an angle of attack close to the optimal of the steady flight of the same wing. With the reduced number of parameters, the aerodynamic cost function in the parameter space can be visualized. This was examined for wings of different lift and drag characteristics at Reynolds numbers between 10(2) and 10(6). The iso-surfaces of the cost function have a tube-like structure, implying that the solution is insensitive to a specific direction in the parameter space. Related questions in insect flight that motivated this work are discussed.

  12. Animal models for radiation injury, protection and therapy.

    Science.gov (United States)

    Augustine, Alison Deckhut; Gondré-Lewis, Timothy; McBride, William; Miller, Lara; Pellmar, Terry C; Rockwell, Sara

    2005-07-01

    Current events throughout the world underscore the growing threat of different forms of terrorism, including radiological or nuclear attack. Pharmaceutical products and other approaches are needed to protect the civilian population from radiation and to treat those with radiation-induced injuries. In the event of an attack, radiation exposures will be heterogeneous in terms of both dose and quality, depending on the type of device used and each victim's location relative to the radiation source. Therefore, methods are needed to protect against and treat a wide range of early and slowly developing radiation-induced injuries. Equally important is the development of rapid and accurate biodosimetry methods for estimating radiation doses to individuals and guiding clinical treatment decisions. Acute effects of high-dose radiation include hematopoietic cell loss, immune suppression, mucosal damage (gastrointestinal and oral), and potential injury to other sites such as the lung, kidney and central nervous system (CNS). Long-term effects, as a result of both high- and low-dose radiation, include dysfunction or fibrosis in a wide range of organs and tissues and cancer. The availability of appropriate types of animal models, as well as adequate numbers of animals, is likely to be a major bottleneck in the development of new or improved radioprotectors, mitigators and therapeutic agents to prevent or treat radiation injuries and of biodosimetry methods to measure radiation doses to individuals.

  13. Animal Models for Studying Triazole Resistance in Aspergillus fumigatus.

    Science.gov (United States)

    Lewis, Russell E; Verweij, Paul E

    2017-08-15

    Infections caused by triazole-resistant Aspergillus fumigatus are associated with a higher probability of treatment failure and mortality. Because clinical experience in managing these infections is still limited, mouse models of invasive aspergillosis fulfill a critical void for studying treatment regimens designed to overcome resistance. The type of immunosuppression, the route of infection, the timing of antifungal administration, and the end points used to assess antifungal activity affect the interpretation of data from these models. Nevertheless, these models provide important insights that help guide treatment decisions in patients with triazole-resistant invasive aspergillosis. Animal models confirmed that a high triazole minimal inhibitory concentration corresponded with triazole treatment failure and that the efficacy of other classes of drugs, such as the polyenes and echinocandins, was not affected by the presence of triazole resistance mutations. Furthermore, the feasibility of triazole dose escalation, combination therapy, and prophylaxis were explored as strategies to overcome resistance. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  14. Modelling Ischemic Stroke and Temperature Intervention Using Vascular Porous Method

    Science.gov (United States)

    Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael

    2017-11-01

    In the event of cerebral infarction, a region of tissue is supplied with insufficient blood flow to support normal metabolism. This can lead to an ischemic reaction which incurs cell death. Through a reduction of temperature, the metabolic demand can be reduced, which then offsets the onset of necrosis. This allows extra time for the patient to receive medical attention and could help prevent permanent brain damage from occurring. Here, we present a vascular-porous (VaPor) blood flow model that can simulate such an event. Cerebral blood flow is simulated using a combination of 1-Dimensional vessels embedded in 3-Dimensional porous media. This allows for simple manipulation of the structure and determining the effect of an obstructed vessel. Results show regional temperature increase of 1-1.5°C comparable with results from literature (in contrast to previous simpler models). Additionally, the application of scalp cooling in such an event dramatically reduces the temperature in the affected region to near hypothermic temperatures, which points to a potential rapid form of first intervention.

  15. Neurorestoratology evidence in an animal model with cervical spondylotic myelopathy

    Directory of Open Access Journals (Sweden)

    Li X

    2017-01-01

    Full Text Available Xiang Li,1,2 Guangsheng Li,1,3 Keith Dip-Kei Luk,1 Yong Hu1–3 1Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong, 2Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 3Spinal Division, Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, Guangdong, People’s Republic of China Background: Cervical spondylotic myelopathy (CSM is a chronic compression injury of the spinal cord, with potentially reversible conditions after surgical decompression, and a unique model of incomplete spinal cord injury. Several animal studies showed pathological changes of demyelination, axon loss and neuron apoptosis in rats with chronic spinal cord compression. However, there is a limited understanding of the neurological change in the spinal cord after surgical decompression. The aim of this study was to validate the neurorestoratology of myelopathic lesions in the spinal cord in a rat model. Materials and methods: A total of 16 adult Sprague-Dawley rats were divided into four groups: sham control (group 1; CSM model with 4-week chronic compression (group 2, 2 weeks (group 3 and 4 weeks (group 4 after surgical decompression of CSM model. The compression and decompression were verified by magnetic resonance imaging (MRI test. Neurological function was evaluated by Basso, Beattie, and Bresnahan (BBB locomotor rating scale, ladder rung walking test and somatosensory-evoked potentials (SEPs. Neuropathological change was evaluated by histological examinations. Results: MRI confirmed the compression of the cervical spinal cord as well as the reshaping of cord morphology after decompression. After decompression, significant changes of neurological function were observed in BBB scores (p < 0.01, F = 10.52, ladder rung walking test (p < 0.05, F = 14.21 and latencies (p < 0.05, F = 5.76 and amplitudes (p < 0.05, F = 3.8 of

  16. Mechanisms and genes in human strial presbycusis from animal models.

    Science.gov (United States)

    Ohlemiller, Kevin K

    2009-06-24

    Schuknecht proposed a discrete form of presbycusis in which hearing loss results principally from degeneration of cochlear stria vascularis and decline of the endocochlear potential (EP). This form was asserted to be genetically linked, and to arise independently from age-related pathology of either the organ of Corti or cochlear neurons. Although extensive strial degeneration in humans coincides with hearing loss, EPs have never been measured in humans, and age-related EP reduction has never been verified. No human genes that promote strial presbycusis have been identified, nor is its pathophysiology well understood. Effective application of animal models to this issue requires models demonstrating EP decline, and preferably, genetically distinct strains that vary in patterns of EP decline and its cellular correlates. Until recently, only two models, Mongolian gerbils and Tyrp1(B-lt) mice, were known to undergo age-associated EP reduction. Detailed studies of seven inbred mouse strains have now revealed three strains (C57BL/6J, B6.CAST-Cdh23(CAST), CBA/J) showing essentially no EP decline with age, and four strains ranging from modest to severe EP reduction (C57BL/6-Tyr(c-2J), BALB/cJ, CBA/CaJ, NOD.NON-H2(nbl)/LtJ). Collectively, animal models support five basic principles regarding a strial form of presbycusis: 1) Progressive EP decline from initially normal levels as a defining characteristic; 2) Non-universality, not all age-associated hearing loss involves EP decline; 3) A clear genetic basis; 4) Modulation by environment or stochastic events; and 5) Independent strial, organ of Corti, and neural pathology. Shared features between human strial presbycusis, gerbils, and BALB/cJ and C57BL/6-Tyr(c-2J) mice further suggest this condition frequently begins with strial marginal cell dysfunction and loss. By contrast, NOD.NON-H2(nbl) mice may model a sequence more closely associated with strial microvascular disease. Additional studies of these and other inbred mouse

  17. Large animal models of rare genetic disorders: sheep as phenotypically relevant models of human genetic disease.

    Science.gov (United States)

    Pinnapureddy, Ashish R; Stayner, Cherie; McEwan, John; Baddeley, Olivia; Forman, John; Eccles, Michael R

    2015-09-02

    Animals that accurately model human disease are invaluable in medical research, allowing a critical understanding of disease mechanisms, and the opportunity to evaluate the effect of therapeutic compounds in pre-clinical studies. Many types of animal models are used world-wide, with the most common being small laboratory animals, such as mice. However, rodents often do not faithfully replicate human disease, despite their predominant use in research. This discordancy is due in part to physiological differences, such as body size and longevity. In contrast, large animal models, including sheep, provide an alternative to mice for biomedical research due to their greater physiological parallels with humans. Completion of the full genome sequences of many species, and the advent of Next Generation Sequencing (NGS) technologies, means it is now feasible to screen large populations of domesticated animals for genetic variants that resemble human genetic diseases, and generate models that more accurately model rare human pathologies. In this review, we discuss the notion of using sheep as large animal models, and their advantages in modelling human genetic disease. We exemplify several existing naturally occurring ovine variants in genes that are orthologous to human disease genes, such as the Cln6 sheep model for Batten disease. These, and other sheep models, have contributed significantly to our understanding of the relevant human disease process, in addition to providing opportunities to trial new therapies in animals with similar body and organ size to humans. Therefore sheep are a significant species with respect to the modelling of rare genetic human disease, which we summarize in this review.

  18. Positive effects of intermittent fasting in ischemic stroke.

    Science.gov (United States)

    Fann, David Yang-Wei; Ng, Gavin Yong Quan; Poh, Luting; Arumugam, Thiruma V

    2017-03-01

    Intermittent fasting (IF) is a dietary protocol where energy restriction is induced by alternate periods of ad libitum feeding and fasting. Prophylactic intermittent fasting has been shown to extend lifespan and attenuate the progress and severity of age-related diseases such as cardiovascular (e.g. stroke and myocardial infarction), neurodegenerative (e.g. Alzheimer's disease and Parkinson's disease) and cancerous diseases in animal models. Stroke is the second leading cause of death, and lifestyle risk factors such as obesity and physical inactivity have been associated with elevated risks of stroke in humans. Recent studies have shown that prophylactic IF may mitigate tissue damage and neurological deficit following ischemic stroke by a mechanism(s) involving suppression of excitotoxicity, oxidative stress, inflammation and cell death pathways in animal stroke models. This review summarizes data supporting the potential hormesis mechanisms of prophylactic IF in animal models, and with a focus on findings from animal studies of prophylactic IF in stroke in our laboratory. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Drug-induced Hypothermia by 5HT1A Agonists Provide Neuroprotection in Experimental Stroke

    DEFF Research Database (Denmark)

    Johansen, Flemming Fryd; Hasseldam, Henrik; Nybro Smith, Matthias

    2014-01-01

    BACKGROUND: Drug-induced hypothermia reduces brain damage in animal stroke models and is an undiscovered potential in human stroke treatment. We studied hypothermia induced by the serotonergic agonists S14671 (1-[2-(2-thenoylamino)ethyl]-4[1-(7- methoxynaphtyl)]piperazine) and ipsapirone in a rat...

  20. Sound preference test in animal models of addicts and phobias.

    Science.gov (United States)

    Soga, Ryo; Shiramatsu, Tomoyo I; Kanzaki, Ryohei; Takahashi, Hirokazu

    2016-08-01

    Biased or too strong preference for a particular object is often problematic, resulting in addiction and phobia. In animal models, alternative forced-choice tasks have been routinely used, but such preference test is far from daily situations that addicts or phobic are facing. In the present study, we developed a behavioral assay to evaluate the preference of sounds in rodents. In the assay, several sounds were presented according to the position of free-moving rats, and quantified the sound preference based on the behavior. A particular tone was paired with microstimulation to the ventral tegmental area (VTA), which plays central roles in reward processing, to increase sound preference. The behaviors of rats were logged during the classical conditioning for six days. Consequently, some behavioral indices suggest that rats search for the conditioned sound. Thus, our data demonstrated that quantitative evaluation of preference in the behavioral assay is feasible.

  1. Practical application of stereological methods in experimental kidney animal models.

    Science.gov (United States)

    Fernández García, María Teresa; Núñez Martínez, Paula; García de la Fuente, Vanessa; Sánchez Pitiot, Marta; Muñiz Salgueiro, María Del Carmen; Perillán Méndez, Carmen; Argüelles Luis, Juan; Astudillo González, Aurora

    The kidneys are vital organs responsible for excretion, fluid and electrolyte balance and hormone production. The nephrons are the kidney's functional and structural units. The number, size and distribution of the nephron components contain relevant information on renal function. Stereology is a branch of morphometry that applies mathematical principles to obtain three-dimensional information from serial, parallel and equidistant two-dimensional microscopic sections. Because of the complexity of stereological studies and the lack of scientific literature on the subject, the aim of this paper is to clearly explain, through animal models, the basic concepts of stereology and how to calculate the main kidney stereological parameters that can be applied in future experimental studies. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Two new animal models for actinide toxicity studies

    International Nuclear Information System (INIS)

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

    1979-01-01

    Two small rodent species, the grasshopper mouse (Onychomys leucogaster) and the deer mouse (Peromyscus maniculatus) have tenacious retention in the liver and skeleton of plutonium and americium. The retention following intraperitoneal injection of Pu and Am in citrate solution ranged from 20 to 47% (liver) and 19 to 42% (skeleton), relatively independent of post-injection times, varying from 30 to 125 days. Based on observations extended to 125 days post-injection, the biological half-times appeared to be long. Both of these rodents are relatively long-lived (median lifespans of approximately 1400 days), breed well in captivity, and adapt suitably to laboratory conditions. It is suggested that these two species of mice, in which plutonium is partitioned between the skeleton and liver in a manner similar to that of man, may be useful animal models for actinide toxicity studies

  3. A large animal model for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Gavin, P.R.; Kraft, S.L.; DeHaan, C.E.; Moore, M.P.; Griebenow, M.L.

    1992-01-01

    An epithermal neutron beam is needed to treat relatively deep seated tumors. The scattering characteristics of neutrons in this energy range dictate that in vivo experiments be conducted in a large animal to prevent unacceptable total body irradiation. The canine species has proven an excellent model to evaluate the various problems of boron neutron capture utilizing an epithermal neutron beam. This paper discusses three major components of the authors study: (1) the pharmacokinetics of borocaptate sodium (NA 2 B 12 H 11 SH or BSH) in dogs with spontaneously occurring brain tumors, (2) the radiation tolerance of normal tissues in the dog using an epithermal beam alone and in combination with borocaptate sodium, and (3) initial treatment of dogs with spontaneously occurring brain tumors utilizing borocaptate sodium and an epithermal neutron beam

  4. Pathogenesis of presbycusis in animal models: a review.

    Science.gov (United States)

    Fetoni, Anna R; Picciotti, Pasqualina M; Paludetti, Gaetano; Troiani, Diana

    2011-06-01

    Presbycusis is the most common cause of hearing loss in aged subjects, reducing individual's communicative skills. Age related hearing loss can be defined as a progressive, bilateral, symmetrical hearing loss due to age related degeneration and it can be considered a multifactorial complex disorder, with both environmental and genetic factors contributing to the aetiology of the disease. The decline in hearing sensitivity caused by ageing is related to the damage at different levels of the auditory system (central and peripheral). Histologically, the aged cochlea shows degeneration of the stria vascularis, the sensorineural epithelium, and neurons of the central auditory pathways. The mechanisms responsible for age-associated hearing loss are still incompletely characterized. This work aims to give a broad overview of the scientific findings related to presbycusis, focusing mainly on experimental studies in animal models. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Animated pose templates for modeling and detecting human actions.

    Science.gov (United States)

    Yao, Benjamin Z; Nie, Bruce X; Liu, Zicheng; Zhu, Song-Chun

    2014-03-01

    This paper presents animated pose templates (APTs) for detecting short-term, long-term, and contextual actions from cluttered scenes in videos. Each pose template consists of two components: 1) a shape template with deformable parts represented in an And-node whose appearances are represented by the Histogram of Oriented Gradient (HOG) features, and 2) a motion template specifying the motion of the parts by the Histogram of Optical-Flows (HOF) features. A shape template may have more than one motion template represented by an Or-node. Therefore, each action is defined as a mixture (Or-node) of pose templates in an And-Or tree structure. While this pose template is suitable for detecting short-term action snippets in two to five frames, we extend it in two ways: 1) For long-term actions, we animate the pose templates by adding temporal constraints in a Hidden Markov Model (HMM), and 2) for contextual actions, we treat contextual objects as additional parts of the pose templates and add constraints that encode spatial correlations between parts. To train the model, we manually annotate part locations on several keyframes of each video and cluster them into pose templates using EM. This leaves the unknown parameters for our learning algorithm in two groups: 1) latent variables for the unannotated frames including pose-IDs and part locations, 2) model parameters shared by all training samples such as weights for HOG and HOF features, canonical part locations of each pose, coefficients penalizing pose-transition and part-deformation. To learn these parameters, we introduce a semi-supervised structural SVM algorithm that iterates between two steps: 1) learning (updating) model parameters using labeled data by solving a structural SVM optimization, and 2) imputing missing variables (i.e., detecting actions on unlabeled frames) with parameters learned from the previous step and progressively accepting high-score frames as newly labeled examples. This algorithm belongs to a

  6. Tissue mechanics, animal models, and pelvic organ prolapse: a review.

    Science.gov (United States)

    Abramowitch, Steven D; Feola, Andrew; Jallah, Zegbeh; Moalli, Pamela A

    2009-05-01

    Pelvic floor disorders such as pelvic organ prolapse, urinary incontinence, and fecal incontinence affect a large number of women each year. The pelvic floor can be thought of as a biomechanical structure due to the complex interaction between the vagina and its supportive structures that are designed to withstand the downward descent of the pelvic organs in response to increases in abdominal pressure. Although previous work has highlighted the biochemical changes that are associated with specific risk factors (i.e. parity, menopause, and genetics), little work has been done to understand the biomechanical changes that occur within the vagina and its supportive structures to prevent the onset of these pelvic floor disorders. Human studies are often limited due to the challenges of obtaining large tissue samples and ethical concerns. Therefore, it is necessary to investigate the use of animal models and their importance in understanding how different risk factors affect the biomechanical properties of the vagina and its supportive structures. In this review paper, we will discuss the different animal models that have been previously used to characterize the biomechanical properties of the vagina: including non-human primates, rodents, rabbits, and sheep. The anatomy and preliminary biomechanical findings are discussed along with the importance of considering experimental conditions, tissue anisotropy, and viscoelasticity when characterizing the biomechanical properties of vaginal tissue. Although there is not a lot of biomechanics research related to the vagina and pelvic floor, the future is exciting due to the significant potential for scientific findings that will improve our understanding of these conditions and hopefully lead to improvements in the prevention and treatment of pelvic disorders.

  7. Studying the Immunomodulatory Effects of Small Molecule Ras Inhibitors in Animal Models of Rheumatoid Arthritis

    Science.gov (United States)

    2017-10-01

    2) and in animal models of human autoimmune diseases including autoimmune colitis (3), experimental autoimmune encephalomyelitis (4), collagen...studied in multiple pre-clinical animal models of autoimmune. For example, FTS can attenuate disease manifestations in experimental autoimmune... experimental animal model of polyarthritis, which can be induced in inbred Lewis rats by immunization with Complete Freund’s adjuvant containing

  8. The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission

    Science.gov (United States)

    Infants and children with tuberculosis (TB) account for more than 20% of cases in endemic countries. Current animal models study TB during adulthood but animal models for adolescent and infant TB are scarce. Here we propose that minipigs can be used as an animal model to study adult, adolescent and ...

  9. Network interactions underlying mirror feedback in stroke: A dynamic causal modeling study

    Directory of Open Access Journals (Sweden)

    Soha Saleh

    2017-01-01

    Full Text Available Mirror visual feedback (MVF is potentially a powerful tool to facilitate recovery of disordered movement and stimulate activation of under-active brain areas due to stroke. The neural mechanisms underlying MVF have therefore been a focus of recent inquiry. Although it is known that sensorimotor areas can be activated via mirror feedback, the network interactions driving this effect remain unknown. The aim of the current study was to fill this gap by using dynamic causal modeling to test the interactions between regions in the frontal and parietal lobes that may be important for modulating the activation of the ipsilesional motor cortex during mirror visual feedback of unaffected hand movement in stroke patients. Our intent was to distinguish between two theoretical neural mechanisms that might mediate ipsilateral activation in response to mirror-feedback: transfer of information between bilateral motor cortices versus recruitment of regions comprising an action observation network which in turn modulate the motor cortex. In an event-related fMRI design, fourteen chronic stroke subjects performed goal-directed finger flexion movements with their unaffected hand while observing real-time visual feedback of the corresponding (veridical or opposite (mirror hand in virtual reality. Among 30 plausible network models that were tested, the winning model revealed significant mirror feedback-based modulation of the ipsilesional motor cortex arising from the contralesional parietal cortex, in a region along the rostral extent of the intraparietal sulcus. No winning model was identified for the veridical feedback condition. We discuss our findings in the context of supporting the latter hypothesis, that mirror feedback-based activation of motor cortex may be attributed to engagement of a contralateral (contralesional action observation network. These findings may have important implications for identifying putative cortical areas, which may be targeted with

  10. Guinea pigs as an animal model for sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Malik Abu Rafee

    2017-01-01

    Full Text Available The overwhelming use of rat models in nerve regeneration studies is likely to induce skewness in treatment outcomes. To address the problem, this study was conducted in 8 adult guinea pigs of either sex to investigate the suitability of guinea pig as an alternative model for nerve regeneration studies. A crush injury was inflicted to the sciatic nerve of the left limb, which led to significant decrease in the pain perception and neurorecovery up to the 4th weak. Lengthening of foot print and shortening of toe spread were observed in the paw after nerve injury. A 3.49 ± 0.35 fold increase in expression of neuropilin 1 (NRP1 gene and 2.09 ± 0.51 fold increase in neuropilin 2 (NRP2 gene were recorded 1 week after nerve injury as compared to the normal nerve. Ratios of gastrocnemius muscle weight and volume of the experimental limb to control limb showed more than 50% decrease on the 30th day. Histopathologically, vacuolated appearance of the nerve was observed with presence of degenerated myelin debris in digestion chambers. Gastrocnemius muscle also showed degenerative changes. Scanning electron microscopy revealed loose and rough arrangement of connective tissue fibrils and presence of large spherical globules in crushed sciatic nerve. The findings suggest that guinea pigs could be used as an alternative animal model for nerve regeneration studies and might be preferred over rats due to their cooperative nature while recording different parameters.

  11. Common Marmosets: A Potential Translational Animal Model of Juvenile Depression

    Directory of Open Access Journals (Sweden)

    Nicole Leite Galvão-Coelho

    2017-09-01

    Full Text Available Major depression is a psychiatric disorder with high prevalence in the general population, with increasing expression in adolescence, about 14% in young people. Frequently, it presents as a chronic condition, showing no remission even after several pharmacological treatments and persisting in adult life. Therefore, distinct protocols and animal models have been developed to increase the understanding of this disease or search for new therapies. To this end, this study investigated the effects of chronic social isolation and the potential antidepressant action of nortriptyline in juvenile Callithrix jacchus males and females by monitoring fecal cortisol, body weight, and behavioral parameters and searching for biomarkers and a protocol for inducing depression. The purpose was to validate this species and protocol as a translational model of juvenile depression, addressing all domain criteria of validation: etiologic, face, functional, predictive, inter-relational, evolutionary, and population. In both sexes and both protocols (IDS and DPT, we observed a significant reduction in cortisol levels in the last phase of social isolation, concomitant with increases in autogrooming, stereotyped and anxiety behaviors, and the presence of anhedonia. The alterations induced by chronic social isolation are characteristic of the depressive state in non-human primates and/or in humans, and were reversed in large part by treatment with an antidepressant drug (nortriptyline. Therefore, these results indicate C. jacchus as a potential translational model of juvenile depression by addressing all criteria of validation.

  12. An animal model of emotional blunting in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Charmaine Y Pietersen

    Full Text Available Schizophrenia is often associated with emotional blunting--the diminished ability to respond to emotionally salient stimuli--particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fear processing. The present article describes a novel animal model of emotional blunting in schizophrenia. This model involves interfering with normal fear processing (classical conditioning in rats by means of acute ketamine administration. We confirm, in a series of experiments comprised of cFos staining, behavioral analysis and neurochemical determinations, that ketamine interferes with the behavioral expression of fear and with normal fear processing in the amygdala and related brain regions. We further show that the atypical antipsychotic drug clozapine, but not the typical antipsychotic haloperidol nor an experimental glutamate receptor 2/3 agonist, inhibits ketamine's effects and retains normal fear processing in the amygdala at a neurochemical level, despite the observation that fear-related behavior is still inhibited due to ketamine administration. Our results suggest that the relative resistance of emotional blunting to drug treatment may be partially due to an inability of conventional therapies to target the multiple anatomical and functional brain systems involved in emotional processing. A conceptual model reconciling our findings in terms of neurochemistry and behavior is postulated and discussed.

  13. Three-dimensional modeler for animated images display system

    International Nuclear Information System (INIS)

    Boubekeur, Rania

    1987-01-01

    The mv3d software allows the modeling and display of three dimensional objects in interpretative mode with animation possibility in real time. This system is intended for a graphical extension of a FORTH interpreter (implemented by CEA/IRDI/D.LETI/DEIN) in order to control a specific hardware (3.D card designed and implemented by DEIN) allowing the generation of three dimensional objects. The object description is carried out with a specific graphical language integrated in the FORTH interpreter. Objects are modeled using elementary solids called basic forms (cube, cone, cylinder...) assembled with classical geometric transformations (rotation, translation and scaling). These basic forms are approximated by plane polygonal facets further divided in triangles. Coordinates of the summits of triangles constitute the geometrical data. These are sent to the 3.D. card for processing and display. Performed processing are: geometrical transformations on display, hidden surface elimination, shading and clipping. The mv3d software is not an entire modeler but a simple, modular and extensible tool, to which other specific functions may be easily added such as: robots motion, collisions... (author) [fr

  14. Animal Models of Autism: An Epigenetic and Environmental Viewpoint

    Directory of Open Access Journals (Sweden)

    Keiko Iwata

    2010-01-01

    Full Text Available Autism is a neurodevelopmental disorder of social behavior, which is more common in males than in females. The causes of autism are unknown; there is evidence for a substantial genetic component, but it is likely that a combination of genetic, environmental and epigenetic factors contribute to its complex pathogenesis. Rodent models that mimic the behavioral deficits of autism can be useful tools for dissecting both the etiology and molecular mechanisms. This review discusses animal models of autism generated by prenatal or neonatal environmental challenges, including virus infection and exposure to valproic acid (VPA or stress. Studies of viral infection models suggest that interleukin-6 can influence fetal development and programming. Prenatal exposure to the histone deacetylase inhibitor VPA has been linked to autism in children, and male VPA-exposed rats exhibit a spectrum of autistic-like behaviors. The experience of prenatal stress produces male-specific behavioral abnormalities in rats. These effects may be mediated by epigenetic modifications such as DNA methylation and histone acetylation resulting in alterations to the transcriptome.

  15. Assessment Model to Identify Patients With Stroke With a High Possibility of Discharge to Home: A Retrospective Cohort Study.

    Science.gov (United States)

    Itaya, Takahiro; Murakami, Yusuke; Ota, Akiko; Nomura, Eiichi; Fukushima, Tomoko; Nishigaki, Masakazu

    2017-10-01

    Discharge planning for inpatients with acute stroke can enhance reasonable use of healthcare resources, as well as improve clinical outcomes and decrease financial burden of patients. Especially, prediction for discharge destination is crucial for discharge planning. This study aimed to develop an assessment model to identify patients with a high possibility of discharge to home after an acute stroke. We reviewed the electronic medical records of 3200 patients with acute stroke who were admitted to a stroke center in Japan between January 1, 2011, and December 31, 2015. The outcome variable was the discharge destination of postacute stroke patients. The predictive variables were identified through logistic regression analysis. Data were divided into 2 data sets: the learning data set (n=2240) for developing the instrument and the test data set (n=960) for evaluating the predictive capability of the model. In all, 1548 (48%) patients were discharged to their homes. Multiple logistic regression analysis identified 5 predictive variables for discharge to home: living situation, type of stroke, functional independence measure motor score on admission, functional independence measure cognitive score on admission, and paresis. The assessment model showed a sensitivity of 85.0% and a specificity of 75.3% with an area under the curve equal to 0.88 (95% confidence interval, 0.86-0.89) when the cutoff point was 10. On evaluating the predictive capabilities, the model showed a sensitivity of 88.0% and a specificity of 68.7% with an area under the curve equal to 0.87 (95% confidence interval, 0.85-0.89). We have developed an assessment model for identifying patients with a high possibility of being discharged to their homes after an acute stroke. This model would be useful for health professionals to adequately plan patients' discharge soon after their admission. © 2017 American Heart Association, Inc.

  16. A New Tube Gastrostomy Model in Animal Experiments

    Directory of Open Access Journals (Sweden)

    Atakan Sezer

    2013-01-01

    Full Text Available Aim: The orogastric route is the most preferred application method in the vast majority of the animal experiments in which application can be achieved by adding the material to the water of the experiment animal, through an orogastric tube or with a surgically managed ostomy. Material and Method: This experiment was constructed with twelve male Sprague-Dawley rats which were randomly assigned to one of two groups consist of control group ( group C, n: 6 and tube gastrostomy group ( group TG, n: 6.A novel and simple gastrostomy tube was derivated from a silicone foley catheter. Tube gastrostomy apparatus was constituted with a silicone foley catheter (6 French. In the group TG an incision was performed, and the stomach was visualized. A 1 cm incision was made in the midline and opening of the peritoneum. Anchoring sutures were placed and anterior gastric wall was lifted. The gastric wall is then opened. The apparatus was placed into the stomach and pulled through from a tunnel under the skin and fixed to the lateral abdominal wall with a 2/0 silk suture. Result: The procedure was ended in the 10th day of experiment. No mortality was observed in group C. The rats were monitored daily and no abnormal behavior consists of self harming incision site, resistance to oral intake or attending to displace. There was statistically significant difference in increasing alanine transaminase level (p<0.05 and decrease in the total protein and body weight (p<0.05 at the group TG at the end of experiment. There was significant increase in urea levels in Group C (p<0.05 at the end of experiment. The statistically significant decrease was observed in the same period in group C between aspartate transaminase, albumin, total protein, and body weight (p<0.05.  Glucose (p=0.047 and aspartate transaminase (p=0.050 level decrease changes and weight loose (p=0.034 from preoperative period to the end of the experiment between gastrostomy and laparotomy groups were

  17. A parsimonious approach to modeling animal movement data.

    Directory of Open Access Journals (Sweden)

    Yann Tremblay

    Full Text Available Animal tracking is a growing field in ecology and previous work has shown that simple speed filtering of tracking data is not sufficient and that improvement of tracking location estimates are possible. To date, this has required methods that are complicated and often time-consuming (state-space models, resulting in limited application of this technique and the potential for analysis errors due to poor understanding of the fundamental framework behind the approach. We describe and test an alternative and intuitive approach consisting of bootstrapping random walks biased by forward particles. The model uses recorded data accuracy estimates, and can assimilate other sources of data such as sea-surface temperature, bathymetry and/or physical boundaries. We tested our model using ARGOS and geolocation tracks of elephant seals that also carried GPS tags in addition to PTTs, enabling true validation. Among pinnipeds, elephant seals are extreme divers that spend little time at the surface, which considerably impact the quality of both ARGOS and light-based geolocation tracks. Despite such low overall quality tracks, our model provided location estimates within 4.0, 5.5 and 12.0 km of true location 50% of the time, and within 9, 10.5 and 20.0 km 90% of the time, for above, equal or below average elephant seal ARGOS track qualities, respectively. With geolocation data, 50% of errors were less than 104.8 km (<0.94 degrees, and 90% were less than 199.8 km (<1.80 degrees. Larger errors were due to lack of sea-surface temperature gradients. In addition we show that our model is flexible enough to solve the obstacle avoidance problem by assimilating high resolution coastline data. This reduced the number of invalid on-land location by almost an order of magnitude. The method is intuitive, flexible and efficient, promising extensive utilization in future research.

  18. Modelling bronchopulmonary dysplasia in animals: arguments for the preterm rabbit model.

    Science.gov (United States)

    Salaets, Thomas; Gie, Andre; Tack, Bieke; Deprest, Jan; Toelen, Jaan

    2017-09-26

    Bronchopulmonary dysplasia (BPD) remains a frequent and disabling consequence of preterm birth, despite the recent advances in neonatal intensive care. There is a need to further improve outcomes and many novel therapeutic or preventive strategies are therefore investigated in animal models. We discuss in this review the aspects of human BPD pathophysiology and phenotype, which ideally should be mimicked by an animal model for this disease. Prematurity remains the common denominator in the heterogeneous spectrum of human BPD, and preterm animal models thus have a clear translational advantage. Additional factors, like excessive oxygen, mechanical ventilation and infection, which frequently have been studied in animal models, can contribute to preterm lung injury however are not indispensable to develop BPD. The phenotype of human BPD is characterized by alveolar developmental arrest with extracellular matrix remodeling, signs of obstructive airway disease and pulmonary vascular disease. Many animal models mimic this phenotype and have their place in BPD research, but results should be interpreted bearing in mind the specific advantages and disadvantages of the model. Term mice and rats are well suited for basic explorative research on specific disease mechanisms, essential for the generation of new hypotheses, while the larger ventilated preterm baboons and lambs provide a good platform for the ultimate translation of these strategies towards clinical application. The preterm rabbit model seems a promising model as it the smallest model that includes a factor of prematurity and has a unique position between the small and large animal models. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Modal Measurements and Model Corrections of A Large Stroke Compliant Mechanism

    Directory of Open Access Journals (Sweden)

    Wijma W.

    2014-08-01

    Full Text Available In modelling flexure based mechanisms, generally flexures are modelled perfectly aligned and nominal values are assumed for the dimensions. To test the validity of these assumptions for a two Degrees Of Freedom (DOF large stroke compliant mechanism, eigenfrequency and mode shape measurements are compared to results obtained with a flexible multibody model. The mechanism consists of eleven cross flexures and seven interconnecting bodies. From the measurements 30% lower eigenfrequencies are observed than those obtained with the model. With a simplified model, it is demonstrated that these differences can be attributed to wrongly assumed leaf spring thickness and misalignment of the leaf springs in the cross flexures. These manufacturing tolerances thus significantly affect the behaviour of the two DOF mechanism, even though it was designed using the exact constraint design principle. This design principle avoids overconstraints to limit internal stresses due to manufacturing tolerances, yet this paper shows clearly that manufacturing imperfections can still result in significantly different dynamic behaviour.

  20. ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

    Directory of Open Access Journals (Sweden)

    Elsy Nalleli Loria-Cervera

    2014-01-01

    Full Text Available Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail are being infected, and different numbers (“low” 1×102 and “high” 1×106 of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

  1. Swirling flow in model of large two-stroke diesel engine

    DEFF Research Database (Denmark)

    Ingvorsen, Kristian Mark; Meyer, Knud Erik; Schnipper, Teis

    2012-01-01

    A scale model of a simplified cylinder in a uniflow scavenged large two-stroke marine diesel engine is constructed to investigate the scavenging process. Angled ports near the bottom of the cylinder liner are uncovered as the piston reaches the bottom dead center. Fresh air enters through the ports...... Velocimetry (PIV) is used to investigate the scavenging flow for cases with both static and moving piston. Measurements are carried out for several cross-sectional planes covering the majority of the cylinder length. The effect of swirl intensity is investigated using four different port angles going from 0...

  2. Genetic Aspects of Autism Spectrum Disorders: Insights from Animal Models

    Directory of Open Access Journals (Sweden)

    Swati eBanerjee

    2014-02-01

    Full Text Available Autism spectrum disorders (ASD are a complex neurodevelopmental disorder that display a triad of core behavioral deficits including restricted interests, often accompanied by repetitive behavior, deficits in language and communication, and an inability to engage in reciprocal social interactions. ASD is among the most heritable disorders but is not a simple disorder with a singular pathology and has a rather complex etiology. It is interesting to note that perturbations in synaptic growth, development and stability underlie a variety of neuropsychiatric disorders, including ASD, schizophrenia, epilepsy and intellectual disability. Biological characterization of an increasing repertoire of synaptic mutants in various model organisms indicates synaptic dysfunction as causal in the pathophysiology of ASD. Our understanding of the genes and genetic pathways that contribute towards the formation, stabilization and maintenance of functional synapses coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics is therefore essential to unraveling the pathogenesis of these disorders. In this review, we discuss the genetic aspects of ASD emphasizing on the well conserved set of genes and genetic pathways implicated in this disorder, many of which contribute to synapse assembly and maintenance across species. We also review how fundamental research using animal models is providing key insights into the various facets of human ASD.

  3. Neuropathology and Animal Models of Autism: Genetic and Environmental Factors

    Directory of Open Access Journals (Sweden)

    Bharathi S. Gadad

    2013-01-01

    Full Text Available Autism is a heterogeneous behaviorally defined neurodevelopmental disorder. It is defined by the presence of marked social deficits, specific language abnormalities, and stereotyped repetitive patterns of behavior. Because of the variability in the behavioral phenotype of the disorder among patients, the term autism spectrum disorder has been established. In the first part of this review, we provide an overview of neuropathological findings from studies of autism postmortem brains and identify the cerebellum as one of the key brain regions that can play a role in the autism phenotype. We review research findings that indicate possible links between the environment and autism including the role of mercury and immune-related factors. Because both genes and environment can alter the structure of the developing brain in different ways, it is not surprising that there is heterogeneity in the behavioral and neuropathological phenotypes of autism spectrum disorders. Finally, we describe animal models of autism that occur following insertion of different autism-related genes and exposure to environmental factors, highlighting those models which exhibit both autism-like behavior and neuropathology.

  4. What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Consideration of Strategies to Improve the Value of Animal Models.

    Science.gov (United States)

    Herati, Ramin Sedaghat; Wherry, E John

    2018-04-02

    Animal models are an essential feature of the vaccine design toolkit. Although animal models have been invaluable in delineating the mechanisms of immune function, their precision in predicting how well specific vaccines work in humans is often suboptimal. There are, of course, many obvious species differences that may limit animal models from predicting all details of how a vaccine works in humans. However, careful consideration of which animal models may have limitations should also allow more accurate interpretations of animal model data and more accurate predictions of what is to be expected in clinical trials. In this article, we examine some of the considerations that might be relevant to cross-species extrapolation of vaccine-related immune responses for the prediction of how vaccines will perform in humans. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  5. On Practical Implementation of Electromagnetic Models of Lightning Return-Strokes

    Directory of Open Access Journals (Sweden)

    Hamidreza Karami

    2016-10-01

    Full Text Available In electromagnetic models, the return-stroke channel is represented as an antenna excited at its base by either a voltage or a current source. To adjust the speed of the current pulse propagating in the channel to available optical observations, different representations for the return-stroke channel have been proposed in the literature using different techniques to artificially reduce the propagation speed of the current pulse to values consistent with observations. In this paper, we present an analysis of the available electromagnetic models in terms of their practical implementation. Criteria used for the analysis are the ease of implementation of the models, the numerical accuracy and the needed computer resources, as well as their ability to reproduce a desired value for the speed of the return stroke current pulse. Using the CST-MWS software, which is based on the time-domain finite-integration technique, different electromagnetic models were analyzed, namely (A a wire embedded in a fictitious half-space dielectric medium (other than air, (B a wire embedded in a fictitious coating with permittivity (εr and permeability (μr, and (C a wire in free-space loaded by distributed series inductance and resistance. It is shown that, by adjusting the parameters of each model, it is possible to reproduce a desired value for the speed of the current pulse. For each of the considered models, we determined the values for the adjustable parameters that allow obtaining the desired value of the return speed. Model A is the least expensive in terms of computing resources. However, it requires two simulation runs to obtain the electromagnetic fields. A variant of Model B that includes a fictitious dielectric/ferromagnetic coating is found to be more efficient to control the current speed along the channel than using only a dielectric coating. On the other hand, this model requires an increased number of mesh cells, resulting in higher memory and

  6. JOURNAL CLUB: Evaluation of Diffusion Kurtosis Imaging of Stroke Lesion With Hemodynamic and Metabolic MRI in a Rodent Model of Acute Stroke.

    Science.gov (United States)

    Lu, Dongshuang; Jiang, Yinghua; Ji, Yang; Zhou, Iris Yuwen; Mandeville, Emiri; Lo, Eng H; Wang, Xiaoying; Sun, Phillip Zhe

    2018-02-22

    Diffusion kurtosis imaging (DKI) has emerged as a new acute stroke imaging approach, augmenting routine DWI. Although it has been shown that a diffusion lesion without kurtosis abnormality is more likely to recover after reperfusion, whereas a kurtosis lesion shows poor response, little is known about the underlying pathophysiologic profile of the kurtosis lesion versus the kurtosis lesion-diffusion lesion mismatch. We performed multiparametric MRI, including arterial spin labeling, pH-sensitive amide proton transfer, and DKI, in a rodent model of acute stroke caused by embolic middle cerebral artery occlusion. Diffusion and kurtosis lesions were semiautomatically segmented, and multiparametric MRI indexes were compared among the kurtosis lesion, diffusion lesion, kurtosis lesion-diffusion lesion mismatch, and the contralateral normal tissue area. We confirmed a significant difference between diffusion lesion and kurtosis lesion volumes (mean [± SD] volume, 151 ± 65 vs 125 ± 47 mm 3 ; p 0.05). Of importance, the pH of the kurtosis lesion was significantly lower than that of the lesion mismatch (mean pH, 6.81 ± 0.08 vs 6.89 ± 0.09; p < 0.01). The present study confirms that DKI provides an expedient approach for refining the heterogeneous DWI lesion that is associated with graded metabolic derangement, which is promising for improving the infarction core definition and ultimately helping to guide stroke treatment.

  7. Small Animal [18F]FDG PET Imaging for Tumor Model Study

    International Nuclear Information System (INIS)

    Woo, Sang Keun; Kim, Kyeong Min; Cheon, Gi Jeong

    2008-01-01

    PET allows non-invasive, quantitative and repetitive imaging of biological function in living animals. Small animal PET imaging with [ 18 F]FDG has been successfully applied to investigation of metabolism, receptor, ligand interactions, gene expression, adoptive cell therapy and somatic gene therapy. Experimental condition of animal handling impacts on the biodistribution of [ 18 F]FDG in small animal study. The small animal PET and CT images were registered using the hardware fiducial markers and small animal contour point. Tumor imaging in small animal with small animal [ 18 F]FDG PET should be considered fasting, warming, and isoflurane anesthesia level. Registered imaging with small animal PET and CT image could be useful for the detection of tumor. Small animal experimental condition of animal handling and registration method will be of most importance for small lesion detection of metastases tumor model

  8. The use of suspension models and comparison with true weightlessness. [Animal Model Workshop on Gravitational Physiology

    Science.gov (United States)

    Musacchia, X. J.; Ellis, S.

    1985-01-01

    A resume is presented of various papers concerning the effect of weightlessness on particular physiological and biochemical phenomena in animal model systems. Findings from weightlessness experiments on earth using suspension models are compared with results of experiments in orbit. The biological phenomena considered include muscle atrophy, changes in the endocrine system, reduction in bone formation, and changes in the cardiovascular system.

  9. Neuropathic pain as a process: reversal of chronification in an animal model

    Directory of Open Access Journals (Sweden)

    Dableh LJ

    2011-09-01

    Full Text Available Liliane J Dableh1,2, Kiran Yashpal1,2, James L Henry1,21Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada; 2Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, CanadaAbstract: Peripheral neuropathic pain arises from trauma to sensory nerves. Other types of acute neurotrauma such as stroke and spinal cord injury are treated immediately, largely to prevent secondary damage. To pursue the possibility that neuropathic pain may also be amenable to early treatment, a rat model of neuropathic pain was induced using a 2-mm polyethylene cuff implanted around one sciatic nerve. Within 24 hours, hypersensitivity to von Frey hair stimulation appeared, as indicated by decreased paw withdrawal thresholds. When the cuff was removed 24 hours after implantation, readings returned to pre-implantation levels starting as early as day 18. When the cuff was removed after 4 days, there was a period of initial hypersensitivity, and then an increase toward baseline at two time points near the end of the study; therefore, only a partial recovery toward pre-implantation values occurred. Having established that a temporal reversal can occur, the next step examined possible pharmacological reversal. The tachykinin NK1 receptor antagonist, CP-96,345, produced a minor increase in withdrawal thresholds in animals with the cuff left permanently implanted. To determine the effect of early and repeated administration of CP-96,345, it was given daily on days 1–4. The cuff was removed on day 4. Six days later, readings showed reversal of tactile hypersensitivity. We suggest that persistent neuropathic pain occurs from processes that develop over several hours and days, and that some of these processes may be prevented by early medical intervention. Thus, nerve injury in the context of chronic neuropathic pain should be treated in a similar manner to nerve injury resulting from stroke, spinal cord

  10. Modeling of the Lightning Plasma Channel Stroke to a Spacecraft during Ascent

    Science.gov (United States)

    Tarditi, Alfonso; Norgard, John

    2009-11-01

    Lightning protection is an important aspect of modern aerospace design: the increased use of composite materials (vs. metals) reduces the shielding and robustness of the conducting path that the outer shell of a vehicle can present to a lightning discharge. A spacecraft during ascent becomes vulnerable to lightning strokes immediately after leaving the launch pad: in addition to natural lightning conditions, there is the possibility of triggered lightning events, caused by a perturbation of the atmospheric electric field [1]. The purpose of this study, in support of the NASA Constellation program, is to determine the evolution of the plasma current and its distribution on the spacecraft surface. Following earlier ``gas dynamic'' approaches [2], the model considers a plasma channel attached to the ascending spacecraft after a return stroke is established. The conductive exhaust plume [3] is an integral part of the model. The NIMROD 3D plasma fluid code [4] is used to model the plasma channel, reproducing the full transient due to the self-consistent magnetic field and the possibility of sweeping of the attachment point along the moving structure [5]. References: [1] M.A. Uman, Proc. IEEE, 76, 1548 (1988). [2] V. A. Rakov, M. A. Uman, IEEE Trans. EMC, EMC-2940, 403 (1998). [3] J. D. Norgard, G.S. Smith, IEEE Trans. EMC, EMC-29, 157 (1987) [4] C. R. Sovinec et al., J. Comput. Phys. 195, 355 (2004). [5] Larsson et al., J. Phys. D, 33, 1876 (2000)

  11. Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy Characterize a Rodent Model of Covert Stroke

    Science.gov (United States)

    Herrera, Sheryl Lyn

    Covert stroke (CS) comprises lesions in the brain often associated by risk factors such as a diet high in fat, salt, cholesterol and sugar (HFSCS). Developing a rodent model for CS incorporating these characteristics is useful for developing and testing interventions. The purpose of this thesis was to determine if magnetic resonance (MR) can detect brain abnormalities to confirm this model will have the desired anatomical effects. Ex vivo MR showed brain abnormalities for rats with the induced lesions and fed the HFSCS diet. Spectra acquired on the fixed livers had an average percent area under the fat peak relative to the water peak of (20+/-4)% for HFSCS and (2+/-2)% for control. In vivo MR images had significant differences between surgeries to induce the lesions (p=0.04). These results show that applying MR identified abnormalities in the rat model and therefore is important in the development of this CS rodent model.

  12. Long-term behavioral assessment of function in an experimental model for ischemic stroke.

    Science.gov (United States)

    Encarnacion, Angelo; Horie, Nobutaka; Keren-Gill, Hadar; Bliss, Tonya M; Steinberg, Gary K; Shamloo, Mehrdad

    2011-03-30

    Middle cerebral artery occlusion (MCAO) in rats is a well-studied experimental model for ischemic stroke leading to brain infarction and functional deficits. Many preclinical studies have focused on a small time window after the ischemic episode to evaluate functional outcome for screening therapeutic candidates. Short evaluation periods following injury have led to significant setbacks due to lack of information on the delayed effects of treatments, as well as short-lived and reversible neuroprotection, so called false-positive results. In this report, we evaluated long-term functional deficit for 90 days after MCAO in two rat strains with two durations of ischemic insult, in order to identify the best experimental paradigm to assess injury and subsequent recovery. Behavioral outcomes were measured pre-MCAO followed by weekly assessment post-stroke. Behavioral tests included the 18-point composite neurological score, 28-point neuroscore, rearing test, vibrissae-evoked forelimb placing test, foot fault test and the CatWalk. Brain lesions were assessed to correlate injury to behavior outcomes at the end of study. Our results indicate that infarction volume in Sprague-Dawley rats was dependent on occlusion duration. In contrast, the infarction volume in Wistar rats did not correlate with the duration of ischemic episode. Functional outcomes were not dependent on occlusion time in either strain; however, measurable deficits were detectable long-term in limb asymmetry, 18- and 28-point neuroscores, forelimb placing, paw swing speed, and gait coordination. In conclusion, these behavioral assays, in combination with an extended long-term assessment period, can be used for evaluating therapeutic candidates in preclinical models of ischemic stroke. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. The Estimation Modelling of Damaged Areas by Harmful Animals

    Science.gov (United States)

    Jang, R.; Sung, M.; Hwang, J.; Jeon, S. W.

    2017-12-01

    The Republic of Korea has undergone rapid development and urban development without sufficient consideration of the environment. This type of growth is accompanied by a reduction in forest area and wildlife habitat. It is a phenomenon that affects the habitat of large mammals more than small. Especially in Korea, the damage caused by wild boar(Sus scrofa) is harsher than other large mammalian species like water deer(Hydropotes inermis), which also means that the number of these reported cases of this species is higher than ones of other mammals. Wild boar has three to eight cubs per year and it is possible to breed every year, which makes it more populous comparing with the fragmented habitats. It could be regarded as one of the top predators in Korea, which it is inevitable for humans to intervene this creature in population control. In addition, some individuals have been forced to be retreated from other habitats in major habitats, or to invade human activity areas for food activity, thereby destroying crops. Ultimately, this mammal species has been treated as farm pest animals through committing road kills and urban emergences. In this study, we has estimated possible farm pest animal present points from the damage district using 2,505 hazardous wildlife damage areas with four types of geological informations, four kinds of forest information, land cover, and distribution of farmland occurred in Gyeongnam province in Korea. In the estimating model, utilizing MAXENT, information of background point was set to 10,000, 70% of the damaged sites were used to construct the model, 30% was used for verification, and 10 times of crossvalidate were proceeded - verified by AUC of ROC. As a result of analyses, AUC was 0.847, and the percent contribution of the forest information was the distance toward inner-forest areas, 36.1%, the land cover, 16.5%, the distance from the field, 14.9%. Furthermore, the permutation importance was 24.9% of the cover, 12.3% of the height

  14. A Spatio-temporal Model of African Animal Trypanosomosis Risk.

    Directory of Open Access Journals (Sweden)

    Ahmadou H Dicko

    Full Text Available African animal trypanosomosis (AAT is a major constraint to sustainable development of cattle farming in sub-Saharan Africa. The habitat of the tsetse fly vector is increasingly fragmented owing to demographic pressure and shifts in climate, which leads to heterogeneous risk of cyclical transmission both in space and time. In Burkina Faso and Ghana, the most important vectors are riverine species, namely Glossina palpalis gambiensis and G. tachinoides, which are more resilient to human-induced changes than the savannah and forest species. Although many authors studied the distribution of AAT risk both in space and time, spatio-temporal models allowing predictions of it are lacking.We used datasets generated by various projects, including two baseline surveys conducted in Burkina Faso and Ghana within PATTEC (Pan African Tsetse and Trypanosomosis Eradication Campaign national initiatives. We computed the entomological inoculation rate (EIR or tsetse challenge using a range of environmental data. The tsetse apparent density and their infection rate were separately estimated and subsequently combined to derive the EIR using a "one layer-one model" approach. The estimated EIR was then projected into suitable habitat. This risk index was finally validated against data on bovine trypanosomosis. It allowed a good prediction of the parasitological status (r2 = 67%, showed a positive correlation but less predictive power with serological status (r2 = 22% aggregated at the village level but was not related to the illness status (r2 = 2%.The presented spatio-temporal model provides a fine-scale picture of the dynamics of AAT risk in sub-humid areas of West Africa. The estimated EIR was high in the proximity of rivers during the dry season and more widespread during the rainy season. The present analysis is a first step in a broader framework for an efficient risk management of climate-sensitive vector-borne diseases.

  15. Integrated Analysis of Expression Profile Based on Differentially Expressed Genes in Middle Cerebral Artery Occlusion Animal Models

    Directory of Open Access Journals (Sweden)

    Huaqiang Zhou

    2016-05-01

    Full Text Available Stroke is one of the most common causes of death, only second to heart disease. Molecular investigations about stroke are in acute shortage nowadays. This study is intended to explore a gene expression profile after brain ischemia reperfusion. Meta-analysis, differential expression analysis, and integrated analysis were employed on an eight microarray series. We explored the functions and pathways of target genes in gene ontology (GO enrichment analysis and constructed a protein-protein interaction network. Meta-analysis identified 360 differentially expressed genes (DEGs for Mus musculus and 255 for Rattus norvegicus. Differential expression analysis identified 44 DEGs for Mus musculus and 21 for Rattus norvegicus. Timp1 and Lcn2 were overexpressed in both species. The cytokine-cytokine receptor interaction and chemokine signaling pathway were highly enriched for the Kyoto Encyclopedia of Genes and Genomes (KEGG pathway. We have exhibited a global view of the potential molecular differences between middle cerebral artery occlusion (MCAO animal model and sham for Mus musculus or Rattus norvegicus, including the biological process and enriched pathways in DEGs. This research helps contribute to a clearer understanding of the inflammation process and accurate identification of ischemic infarction stages, which might be transformed into a therapeutic approach.

  16. Magnetic inductive phase shift: a new method to differentiate hemorrhagic stroke from ischemic stroke on rabbit.

    Science.gov (United States)

    Yan, Qingguang; Jin, Gui; Ma, Ke; Qin, Mingxin; Zhuang, Wei; Sun, Jian

    2017-05-30

    The major therapy for ischemic stroke is thrombolytic treatment, but severe consequences occur when this method is used to treat hemorrhagic stroke. Currently, computed tomography and magnetic resonance imaging are used to differentiate between two types of stroke, but these two methods are ineffective for pre-hospital care. We developed a new brain diagnostic device for rabbits based on electromagnetic induction to non-invasively differentiate two types of stroke. The device includes two coils and a phase difference measurement system that detects the magnetic inductive phase shift (MIPS) value to reflect the tissue's condition. The hemorrhage model was established through the injection of autologous blood into the internal capsule of a rabbit's brain. Ischemia was induced in the brain of a rabbit by bilateral carotid artery occlusion. Two types of animal models were measured with our device. The MIPS value gradually decreased with increasing injected blood and increased with ischemia time. The MIPS changes induced by the two types of strokes were exact opposites, and the absolute values of MIPS variation in the hemorrhagic and the ischemic groups were significantly larger than those of the normal control group (P stroke from hemorrhagic stroke on rabbit brain in a non-invasive, continuous, and bulk monitoring manner by using a simple and inexpensive apparatus.

  17. The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals.

    Science.gov (United States)

    van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan

    2015-07-15

    Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Animal models in surgical training: choice and ethics | Hassan ...

    African Journals Online (AJOL)

    The use of animals in scientific research dates back to 500 BC, with research from Greece by Alcmaeon and other temporary scientists. Techniques for dissecting living animals were improved by Galen of Pergamum and his experiments were later valuable in the discovery of blood circulation in the16th century. Until the ...

  19. Development of computational small animal models and their applications in preclinical imaging and therapy research

    NARCIS (Netherlands)

    Xie, Tianwu; Zaidi, Habib

    The development of multimodality preclinical imaging techniques and the rapid growth of realistic computer simulation tools have promoted the construction and application of computational laboratory animal models in preclinical research. Since the early 1990s, over 120 realistic computational animal

  20. An overview of animal models of pain: disease models and outcome measures

    Science.gov (United States)

    Gregory, N; Harris, AL; Robinson, CR; Dougherty, PM; Fuchs, PN; Sluka, KA

    2013-01-01

    Pain is ultimately a perceptual phenomenon. It is built from information gathered by specialized pain receptors in tissue, modified by spinal and supraspinal mechanisms, and integrated into a discrete sensory experience with an emotional valence in the brain. Because of this, studying intact animals allows the multidimensional nature of pain to be examined. A number of animal models have been developed, reflecting observations that pain phenotypes are mediated by distinct mechanisms. Animal models of pain are designed to mimic distinct clinical diseases to better evaluate underlying mechanisms and potential treatments. Outcome measures are designed to measure multiple parts of the pain experience including reflexive hyperalgesia measures, sensory and affective dimensions of pain and impact of pain on function and quality of life. In this review we discuss the common methods used for inducing each of the pain phenotypes related to clinical pain syndromes, as well as the main behavioral tests for assessing pain in each model. PMID:24035349

  1. Towards an Evolutionary Model of Animal-Associated Microbiomes

    Directory of Open Access Journals (Sweden)

    Bryan A. White

    2011-02-01

    Full Text Available Second-generation sequencing technologies have granted us greater access to the diversity and genetics of microbial communities that naturally reside endo- and ecto-symbiotically with animal hosts. Substantial research has emerged describing the diversity and broader trends that exist within and between host species and their associated microbial ecosystems, yet the application of these data to our evolutionary understanding of microbiomes appears fragmented. For the most part biological perspectives are based on limited observations of oversimplified communities, while mathematical and/or computational modeling of these concepts often lack biological precedence. In recognition of this disconnect, both fields have attempted to incorporate ecological theories, although their applicability is currently a subject of debate because most ecological theories were developed based on observations of macro-organisms and their ecosystems. For the purposes of this review, we attempt to transcend the biological, ecological and computational realms, drawing on extensive literature, to forge a useful framework that can, at a minimum be built upon, but ideally will shape the hypotheses of each field as they move forward. In evaluating the top-down selection pressures that are exerted on a microbiome we find cause to warrant reconsideration of the much-maligned theory of multi-level selection and reason that complexity must be underscored by modularity.

  2. Environmental enrichment facilitates cocaine abstinence in an animal conflict model.

    Science.gov (United States)

    Ewing, Scott; Ranaldi, Robert

    2018-03-01

    In this study, we sought to discover if housing in an enriched environment (EE) is an efficacious intervention for encouraging abstinence from cocaine seeking in an animal "conflict" model of abstinence. Sixteen Long-Evans rats were trained in 3-h daily sessions to self-administer a cocaine solution (1 mg/kg/infusion) until each demonstrated a stable pattern of drug-seeking. Afterward, half were placed in EE cages equipped with toys, obstacles, and a running wheel, while the other half were given clean, standard laboratory housing. All rats then completed daily 30-min sessions during which the 2/3 of flooring closest to the self-administration levers was electrified, causing discomfort should they approach the levers; current strength (mA) was increased after every day of drug seeking until the rat ceased activity on the active lever for 3 consecutive sessions (abstinence). Rats housed in EE abstained after fewer days and at lower current strengths than rats in standard housing. These results support the idea that EE administered after the development of a cocaine-taking habit may be an effective strategy to facilitate abstinence. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Cytokines and VEGF Induction in Orthodontic Movement in Animal Models

    Directory of Open Access Journals (Sweden)

    M. Di Domenico

    2012-01-01

    Full Text Available Orthodontics is a branch of dentistry that aims at the resolution of dental malocclusions. The specialist carries out the treatment using intraoral or extraoral orthodontic appliances that require forces of a given load level to obtain a tooth movement in a certain direction in dental arches. Orthodontic tooth movement is dependent on efficient remodeling of periodontal ligament and alveolar bone, correlated with several biological and mechanical responses of the tissues surrounding the teeth. A periodontal ligament placed under pressure will result in bone resorption whereas a periodontal ligament under tension results in bone formation. In the primary stage of the application of orthodontic forces, an acute inflammation occurs in periodontium. Several proinflammatory cytokines are produced by immune-competent cells migrating by means of dilated capillaries. In this paper we summarize, also through the utilization of animal models, the role of some of these molecules, namely, interleukin-1β and vascular endothelial growth factor, that are some proliferation markers of osteoclasts and osteoblasts, and the macrophage colony stimulating factor.

  4. Food Addiction and Binge Eating: Lessons Learned from Animal Models

    Science.gov (United States)

    Diéguez, Carlos

    2018-01-01

    The feeding process is required for basic life, influenced by environment cues and tightly regulated according to demands of the internal milieu by regulatory brain circuits. Although eating behaviour cannot be considered “addictive” under normal circumstances, people can become “addicted” to this behaviour, similarly to how some people are addicted to drugs. The symptoms, cravings and causes of “eating addiction” are remarkably similar to those experienced by drug addicts, and both drug-seeking behaviour as eating addiction share the same neural pathways. However, while the drug addiction process has been highly characterised, eating addiction is a nascent field. In fact, there is still a great controversy over the concept of “food addiction”. This review aims to summarize the most relevant animal models of “eating addictive behaviour”, emphasising binge eating disorder, that could help us to understand the neurobiological mechanisms hidden under this behaviour, and to improve the psychotherapy and pharmacological treatment in patients suffering from these pathologies. PMID:29324652

  5. Food Addiction and Binge Eating: Lessons Learned from Animal Models

    Directory of Open Access Journals (Sweden)

    Marta G. Novelle

    2018-01-01

    Full Text Available The feeding process is required for basic life, influenced by environment cues and tightly regulated according to demands of the internal milieu by regulatory brain circuits. Although eating behaviour cannot be considered “addictive” under normal circumstances, people can become “addicted” to this behaviour, similarly to how some people are addicted to drugs. The symptoms, cravings and causes of “eating addiction” are remarkably similar to those experienced by drug addicts, and both drug-seeking behaviour as eating addiction share the same neural pathways. However, while the drug addiction process has been highly characterised, eating addiction is a nascent field. In fact, there is still a great controversy over the concept of “food addiction”. This review aims to summarize the most relevant animal models of “eating addictive behaviour”, emphasising binge eating disorder, that could help us to understand the neurobiological mechanisms hidden under this behaviour, and to improve the psychotherapy and pharmacological treatment in patients suffering from these pathologies.

  6. MeCP2-Related Diseases and Animal Models

    Directory of Open Access Journals (Sweden)

    Chinelo D. Ezeonwuka

    2014-01-01

    Full Text Available The role of epigenetics in human disease has become an area of increased research interest. Collaborative efforts from scientists and clinicians have led to a better understanding of the molecular mechanisms by which epigenetic regulation is involved in the pathogenesis of many human diseases. Several neurological and non-neurological disorders are associated with mutations in genes that encode for epigenetic factors. One of the most studied proteins that impacts human disease and is associated with deregulation of epigenetic processes is Methyl CpG binding protein 2 (MeCP2. MeCP2 is an epigenetic regulator that modulates gene expression by translating epigenetic DNA methylation marks into appropriate cellular responses. In order to highlight the importance of epigenetics to development and disease, we will discuss how MeCP2 emerges as a key epigenetic player in human neurodevelopmental, neurological, and non-neurological disorders. We will review our current knowledge on MeCP2-related diseases, including Rett Syndrome, Angelman Syndrome, Fetal Alcohol Spectrum Disorder, Hirschsprung disease, and Cancer. Additionally, we will briefly discuss about the existing MeCP2 animal models that have been generated for a better understanding of how MeCP2 impacts certain human diseases.

  7. Microsurgical tunica albuginea transplantation in an animal model

    Directory of Open Access Journals (Sweden)

    Salvatore Sansalone

    2017-01-01

    Full Text Available Several andrological diseases require surgical repair or reconstruction of tunica albuginea, which envelops the corpora cavernosa penis. Despite intense research efforts involving a variety of biological materials, such as skin, muscle aponeurosis, human dura mater, tunica vaginalis, and pericardium, engineered tunica albuginea suitable for graft use is yet to be obtained. The study investigates microsurgical tunica albuginea allotransplantation in an animal model with the purpose of creation of an organ-specific tissue bank to store penile tissue, from cadaveric donors and male-to-female trans-sexual surgery, for allogeneic transplantation. Materials were tunica albuginea tissue explanted from 15 donor rats, cryopreserved at −80°C, gamma-irradiated, and implanted in 15 recipient rats, of which three rats were used as controls. Penile grafts were explanted at different time intervals; after macroscopic evaluation of the organ, the grafts were processed to morphological, histochemical, and immunohistochemical examinations by light microscopy. Detection of pro-inflammatory cytokines was also performed. Examination of the tunica albuginea allografts collected 1, 3, or 6 months after surgery and of control tunica albuginea fragments showed that tunica albuginea implants achieved biointegration with adjacent tissue at all-time points. The integration of cryopreserved rat tunica albuginea allografts, documented by our study, encourages the exploration of tunica albuginea allotransplantation in humans. In conclusion, the effectiveness and reliability of the tunica albuginea conditioning protocol described here suggest the feasibility of setting up a tunica albuginea bank as a further tissue bank.

  8. Microsurgical tunica albuginea transplantation in an animal model

    Science.gov (United States)

    Sansalone, Salvatore; Loreto, Carla; Leonardi, Rosario; Vespasiani, Giuseppe; Musumeci, Giuseppe; Lombardo, Claudia; Castorina, Sergio; Cardile, Venera; Caltabiano, Rosario

    2017-01-01

    Several andrological diseases require surgical repair or reconstruction of tunica albuginea, which envelops the corpora cavernosa penis. Despite intense research efforts involving a variety of biological materials, such as skin, muscle aponeurosis, human dura mater, tunica vaginalis, and pericardium, engineered tunica albuginea suitable for graft use is yet to be obtained. The study investigates microsurgical tunica albuginea allotransplantation in an animal model with the purpose of creation of an organ-specific tissue bank to store penile tissue, from cadaveric donors and male-to-female trans-sexual surgery, for allogeneic transplantation. Materials were tunica albuginea tissue explanted from 15 donor rats, cryopreserved at −80°C, gamma-irradiated, and implanted in 15 recipient rats, of which three rats were used as controls. Penile grafts were explanted at different time intervals; after macroscopic evaluation of the organ, the grafts were processed to morphological, histochemical, and immunohistochemical examinations by light microscopy. Detection of pro-inflammatory cytokines was also performed. Examination of the tunica albuginea allografts collected 1, 3, or 6 months after surgery and of control tunica albuginea fragments showed that tunica albuginea implants achieved biointegration with adjacent tissue at all-time points. The integration of cryopreserved rat tunica albuginea allografts, documented by our study, encourages the exploration of tunica albuginea allotransplantation in humans. In conclusion, the effectiveness and reliability of the tunica albuginea conditioning protocol described here suggest the feasibility of setting up a tunica albuginea bank as a further tissue bank. PMID:28139472

  9. Sex differences in animal models of decision making.

    Science.gov (United States)

    Orsini, Caitlin A; Setlow, Barry

    2017-01-02

    The ability to weigh the costs and benefits of various options to make an adaptive decision is critical to an organism's survival and wellbeing. Many psychiatric diseases are characterized by maladaptive decision making, indicating a need for better understanding of the mechanisms underlying this process and the ways in which it is altered under pathological conditions. Great strides have been made in uncovering these mechanisms, but the majority of what is known comes from studies conducted solely in male subjects. In recent years, decision-making research has begun to include female subjects to determine whether sex differences exist and to identify the mechanisms that contribute to such differences. This Mini-Review begins by describing studies that have examined sex differences in animal (largely rodent) models of decision making. Possible explanations, both theoretical and biological, for such differences in decision making are then considered. The Mini-Review concludes with a discussion of the implications of sex differences in decision making for understanding psychiatric conditions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Sex Differences in Animal Models of Decision-Making

    Science.gov (United States)

    Orsini, Caitlin A.; Setlow, Barry

    2016-01-01

    The ability to weigh the costs and benefits of various options in order to make an adaptive decision is critical to an organism’s survival and well-being. Many psychiatric diseases are characterized by maladaptive decision-making, indicating the need to better understand the mechanisms underlying this process and the ways in which it is altered in pathological conditions. Great strides have been made in uncovering these mechanisms, but the majority of what is known comes from studies conducted solely in male subjects. In recent years, decision-making research has begun to include females to determine whether sex differences exist and to identify the mechanisms that contribute to such differences. This review will begin by describing studies that have examined sex differences in animal (largely rodent) models of decision-making. Possible explanations, both theoretical and biological, for such differences in decision- making will then be considered. The review will conclude with a discussion of the implications of sex differences in decision-making for understanding psychiatric conditions. PMID:27870448

  11. Animal model for schizophrenia that reflects gene-environment interactions.

    Science.gov (United States)

    Nagai, Taku; Ibi, Daisuke; Yamada, Kiyofumi

    2011-01-01

    Schizophrenia is a devastating psychiatric disorder that impairs mental and social functioning and affects approximately 1% of the population worldwide. Genetic susceptibility factors for schizophrenia have recently been reported, some of which are known to play a role in neurodevelopment; these include neuregulin-1, dysbindin, and disrupted-in-schizophrenia 1 (DISC1). Moreover, epidemiologic studies suggest that environmental insults, such as prenatal infection and perinatal complication, are involved in the development of schizophrenia. The possible interaction between environment and genetic susceptibility factors, especially during neurodevelopment, is proposed as a promising disease etiology of schizophrenia. Polyriboinosinic-polyribocytidilic acid (polyI : C) is a synthetic analogue of double-stranded RNA that leads to the pronounced but time-limited production of pro-inflammatory cytokines. Maternal immune activation by polyI : C exposure in rodents is known to precipitate a wide spectrum of behavioral, cognitive, and pharmacological abnormalities in adult offspring. Recently, we have reported that neonatal injection of polyI : C in mice results in schizophrenia-like behavioral alterations in adulthood. In this review, we show how gene-environment interactions during neurodevelopment result in phenotypic changes in adulthood by injecting polyI : C into transgenic mice that express a dominant-negative form of human DISC1 (DN-DISC1). Our findings suggest that polyI : C-treated DN-DISC1 mice are a well-validated animal model for schizophrenia that reflects gene-environment interactions.

  12. Dysbaric osteonecrosis in divers and caisson workers. An animal model.

    Science.gov (United States)

    Lehner, C E; Adams, W M; Dubielzig, R R; Palta, M; Lanphier, E H

    1997-11-01

    Dysbaric osteonecrosis was induced successfully in adult sheep after 12 to 13, 24-hour exposures to compressed air (2.6-2.9 atmospheres absolute) during a 2-month period. All exposed sheep had decompression sickness and extensive bone and marrow necrosis in their long bones. Radiographic analysis of these progressive lesions showed mottled to distinct medullary opacities and endosteal thickening characteristic of dysbaric osteonecrosis. Six months after the last hyperbaric exposure, neovascularization of once ischemic fatty marrow was centripetal from the diaphyseal cortex. Proliferating endosteal new bone, fatty marrow calcification, and appositional new bone formation were widespread. Juxtaarticular osteonecrosis involved marrow fibrosis and loss of osteocytes in subchondral cortical bone. Tidemark reduplication in juxtaarticular bone and cartilage thinning suggested possible early osteoarthritis induction by recurrent episodes of transient ischemia after multiple hyperbaric exposures. Dysbaric osteonecrosis appears to involve a bone compartment syndrome of elevated intramedullary pressure initiated by decompression induced N2 bubble formation in the fatty marrow of the long bones. An animal model that can be used to investigate the pathogenesis, diagnosis, and treatment of dysbaric osteonecrosis is discussed.

  13. Defective membrane remodeling in neuromuscular diseases: insights from animal models.

    Directory of Open Access Journals (Sweden)

    Belinda S Cowling

    Full Text Available Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1, and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1 a common molecular pathway underlying these different neuromuscular diseases, and (2 tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches.

  14. The impact of the postnatal gut microbiota on animal models

    DEFF Research Database (Denmark)

    Hansen, Axel Jacob Kornerup; Ejsing-Duun, Maria; Aasted, Bent

    2007-01-01

    Quality control of laboratory animals has been mostly concentrated on eliminating and securing the absence of specific infections, but event barrier bred laboratory animals harbour a huge number of gut bacteria. There is scientific evidence that the nature of the gut microbiota especially in early...... correlated to factors related to early exposure to microorganisms, e.g. the so-called hygiene hypothesis claims that the increasing human incidence of allergy. T1D, RA and IBD may be due to the lack of such exposure. It is possible today by various molecular techniques to profile the gut microbiota...... of a laboratory animal, and such techniques should be applied to document uniform animals from laboratory animal vendors to secure standardization and thereby lower variation and smaller group sizes....

  15. Decreased integration and information capacity in stroke measured by whole brain models of resting state activity.

    Science.gov (United States)

    Adhikari, Mohit H; Hacker, Carl D; Siegel, Josh S; Griffa, Alessandra; Hagmann, Patric; Deco, Gustavo; Corbetta, Maurizio

    2017-04-01

    While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to

  16. Effect of Saraswatarishta in animal models of behavior despair

    Directory of Open Access Journals (Sweden)

    Reshma R Parekar

    2014-01-01

    Full Text Available Background: Saraswatarishta (SA is a herbo-mineral formulation consisting of 18 plants some of which are Medhyarasayanas. It has been claimed to be useful in treating central nervous system disorders. Objective: To evaluate antidepressant effect of ′Saraswatarishta′(SA alone and in combination with imipramine and fluoxetine in animal models of depression. Materials and Methods: After obtaining IAEC permission, 144 rats (n = 36/part were randomized into 6 groups- Group 1: Distilled water (1 mL, Group 2: Imipramine (30 mg/kg, Group 3: Fluoxetine (10 mg/kg, Group 4: SA (1.8 mL/kg, Group 5: Imipramine + SA, Group 6: Fluoxetine + SA. Effects of study drugs were evaluated in forced swim test (FST with single exposure to FST (Part 1 and repeated exposure for 14 days (Part 2. In Part 3, reserpine was used with FST and effects of study drugs were evaluated against single exposure to FST. Same model was used with repeated exposures to FST (Part 4. In each part, rats were subjected to open field test (OFT for 5 min prior to final FST. The variables measured: Immobility time in FST; line crossing, rearing and defecation in the OFT. Results: In all four parts, individual drugs and combinations thereof produced significant decrease in immobility time as compared to control, and extent of decrease was comparable amongst these groups. However, values for combination of fluoxetine with SA group were found to be lesser than that for individual agents in Parts 2 and 3. Combination of SA with imipramine did not enhance its anti-depressant effect in any of the parts. OFT findings did not vary significantly amongst the study groups. Conclusion: Decreased immobility in FST and absence of generalized stimulation or depression of motor activity in OFT point towards potential antidepressant effect of Saraswatarishta. Its co-administration with fluoxetine showed more promising effects.

  17. Instrumental learning: an animal model for sleep dependent memory enhancement.

    Science.gov (United States)

    Leenaars, Cathalijn H C; Girardi, Carlos E N; Joosten, Ruud N J M A; Lako, Irene M; Ruimschotel, Emma; Hanegraaf, Maaike A J; Dematteis, Maurice; Feenstra, Matthijs G P; Van Someren, Eus J W

    2013-07-15

    The relationship between learning and sleep is multifaceted; learning influences subsequent sleep characteristics, which may in turn influence subsequent memory. Studies in humans indicate that sleep may not only prevent degradation of acquired memories, but even enhance performance without further practice. In a rodent instrumental learning task, individual differences occur in how fast rats learn to associate lever pressing with food reward. Rats habitually sleep between learning sessions, and may differ in this respect. The current study assessed if the instrumental leaning paradigm could serve as a model to study sleep-dependent memory enhancement. Male Wistar rats performed 2 sessions of instrumental learning per day for 1-3 days. Electroencephalography was recorded both before and after the sessions. Sleep deprivation (3 h) was applied between the first and second session in a subgroup of rats. Measurements comprised the number of lever presses in each session, slow wave sleep (SWS) duration, Rapid Eye Movement Sleep (REMS) duration and sleep spindles. Baseline sleep parameters were similar for fast and slow learning rats. Task-exposure increased REMS-duration. The increase in REMS-duration was observed specifically after sessions in which learning occurred, but not after a later session. Sleep deprivation during the 3h period between the initial two sessions interfered with performance enhancement, but did not prevent this in all rats. Our considered movement control protocol induced partial sleep deprivation and also interfered with performance enhancement. The classic instrumental learning task provides a practical model for animal studies on sleep-dependent memory enhancement. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Evolution of animal models in cancer vaccine development.

    Science.gov (United States)

    Wei, Wei-Zen; Jones, Richard F; Juhasz, Csaba; Gibson, Heather; Veenstra, Jesse

    2015-12-16

    Advances in cancer vaccine development are facilitated by animal models reflecting key features of human cancer and its interface with host immunity. Several series of transplantable preneoplastic and neoplastic mouse mammary lesions have been used to delineate mechanisms of anti-tumor immunity. Mimicking immune tolerance to tumor-associated antigens (TAA) such as HER2/neu, transgenic mice developing spontaneous mammary tumors are strong model systems for pre-clinical vaccine testing. In these models, HER2 DNA vaccines are easily administered, well-tolerated, and induce both humoral and cellular immunity. Although engineered mouse strains have advanced cancer immunotherapy, basic shortcomings remain. For example, multiple mouse strains have to be tested to recapitulate genetic regulation of immune tolerance in humans. Outbred domestic felines more closely parallel humans in the natural development of HER2 positive breast cancer and their varying genetic background. Electrovaccination with heterologous HER2 DNA induces robust adaptive immune responses in cats. Importantly, homologous feline HER2 DNA with a single amino acid substitution elicits unique antibodies to feline mammary tumor cells, unlocking a new vaccine principle. As an alternative approach to targeted vaccination, non-surgical tumor ablation such as cryoablation induces anti-tumor immunity via in situ immunization, particularly when combined with toll-like receptor (TLR) agonist. As strategies for vaccination advance, non-invasive monitoring of host response becomes imperative. As an example, magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning following administration of tryptophan metabolism tracer [11C]-alpha-methyl-tryptophan (AMT) provides non-invasive imaging of both tumor growth and metabolic activities. Because AMT is a substrate of indoleamine-pyrrole 2,3-dioxygenase (IDO), an enzyme that produces the immune regulatory molecule kynurenine, AMT imaging can provide

  19. An animal model of differential genetic risk for methamphetamine intake

    Directory of Open Access Journals (Sweden)

    Tamara ePhillips

    2015-09-01

    Full Text Available The question of whether genetic factors contribute to risk for methamphetamine (MA use and dependence has not been intensively investigated. Compared to human populations, genetic animal models offer the advantages of control over genetic family history and drug exposure. Using selective breeding, we created lines of mice that differ in genetic risk for voluntary MA intake and identified the chromosomal addresses of contributory genes. A quantitative trait locus was identified on chromosome 10 that accounts for more than 50% of the genetic variance in MA intake in the selected mouse lines. In addition, behavioral and physiological screening identified differences corresponding with risk for MA intake that have generated hypotheses that are testable in humans. Heightened sensitivity to aversive and certain physiological effects of MA, such as MA-induced reduction in body temperature, are hallmarks of mice bred for low MA intake. Furthermore, unlike MA-avoiding mice, MA-preferring mice are sensitive to rewarding and reinforcing MA effects, and to MA-induced increases in brain extracellular dopamine levels. Gene expression analyses implicate the importance of a network enriched in transcription factor genes, some of which regulate the mu opioid receptor gene, Oprm1, in risk for MA use. Neuroimmune factors appear to play a role in differential response to MA between the mice bred for high and low intake. In addition, chromosome 10 candidate g