Hypoxia adaptation in the cornea: Current animal models and underlying mechanisms

Obstructive sleep apnea (OSA) is known to be independently associated with several cardiovascular diseases including hypertension, myocardial infarction, and stroke. To determine how OSA can increase cardiovascular risk, animal models have been developed to explore the underlying mechanisms and the cellular and end-organ targets of the predominant pathophysiological disturbance in OSA–intermittent hypoxia. Despite several limitations in translating data from animal models to the clinical arena, significant progress has been made in our understanding of how OSA confers increased cardiovascular risk. It is clear now that the hypoxic stress associated with OSA can elicit a broad spectrum of pathological systemic events including sympathetic activation, systemic inflammation, impaired glucose and lipid metabolism, and endothelial dysfunction, among others. This review provides an update of the basic, clinical, and translational advances in our understanding of the metabolic dysfunction and cardiovascular consequences of OSA and highlights the most recent findings and perspectives in the field.

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Chronic stress impacts the cardiovascular system: animal models and clinical outcomes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00859.2014 ◽

2015 ◽

Vol 308 (12) ◽

pp. H1476-H1498 ◽

Cited By ~ 63

Author(s):

Saeid Golbidi ◽

Jefferson C. Frisbee ◽

Ismail Laher

Keyword(s):

Cardiovascular Diseases ◽

Animal Models ◽

Chronic Stress ◽

Laboratory Findings ◽

Important Group ◽

Stress Markers ◽

Random Fashion ◽

Human Stress ◽

Underlying Mechanisms ◽

Psychosomatic Diseases

Psychological stresses are associated with cardiovascular diseases to the extent that cardiovascular diseases are among the most important group of psychosomatic diseases. The longstanding association between stress and cardiovascular disease exists despite a large ambiguity about the underlying mechanisms. An array of possibilities have been proposed including overactivity of the autonomic nervous system and humoral changes, which then converge on endothelial dysfunction that initiates unwanted cardiovascular consequences. We review some of the features of the two most important stress-activated systems, i.e., the humoral and nervous systems, and focus on alterations in endothelial function that could ensue as a result of these changes. Cardiac and hematologic consequences of stress are also addressed briefly. It is likely that activation of the inflammatory cascade in association with oxidative imbalance represents key pathophysiological components of stress-induced cardiovascular changes. We also review some of the commonly used animal models of stress and discuss the cardiovascular outcomes reported in these models of stress. The unique ability of animals for adaptation under stressful conditions lessens the extrapolation of laboratory findings to conditions of human stress. An animal model of unpredictable chronic stress, which applies various stress modules in a random fashion, might be a useful solution to this predicament. The use of stress markers as indicators of stress intensity is also discussed in various models of animal stress and in clinical studies.

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Mouse Models of Schizophrenia and Bipolar Disorder

Neurobiology of Mental Illness ◽

10.1093/med/9780199934959.003.0022 ◽

2013 ◽

pp. 287-300

Author(s):

Mikhail V. Pletnikov ◽

Christopher A. Ross

Keyword(s):

Bipolar Disorder ◽

Animal Models ◽

Mouse Models ◽

Recent Progress ◽

Neuropsychiatric Disorders ◽

Environmental Interventions ◽

The Future ◽

Underlying Mechanisms ◽

Insight Into ◽

Genetic Mouse Models

Despite the recent advances in research into schizophrenia and bipolar disorder, the neurobiology of these maladies remains poorly understood. Animal models can be instrumental in elucidating the underlying mechanisms of neuropsychiatric disorders. Early animal models of schizophrenia and bipolar disorder used lesion methods, pharmacologic challenges or environmental interventions to mimic pathogenic features of the diseases. The recent progress in genetics has stimulated the development of etiological models that have begun to provide insight into pathogenesis. In this review, we evaluate the strengths and weaknesses of the existing genetic mouse models of schizophrenia and discuss potential developments for the future.

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Wireless, battery-free optoelectronic systems as subdermal implants for local tissue oximetry

Science Advances ◽

10.1126/sciadv.aaw0873 ◽

2019 ◽

Vol 5 (3) ◽

pp. eaaw0873 ◽

Cited By ~ 27

Author(s):

Hao Zhang ◽

Philipp Gutruf ◽

Kathleen Meacham ◽

Michael C. Montana ◽

Xingyue Zhao ◽

...

Keyword(s):

Animal Models ◽

Tissue Oxygenation ◽

Human Subjects ◽

Brain Regions ◽

Disease States ◽

Data Output ◽

Subdermal Implants ◽

Underlying Mechanisms ◽

Tissue Oximetry

Monitoring regional tissue oxygenation in animal models and potentially in human subjects can yield insights into the underlying mechanisms of local O2-mediated physiological processes and provide diagnostic and therapeutic guidance for relevant disease states. Existing technologies for tissue oxygenation assessments involve some combination of disadvantages in requirements for physical tethers, anesthetics, and special apparatus, often with confounding effects on the natural behaviors of test subjects. This work introduces an entirely wireless and fully implantable platform incorporating (i) microscale optoelectronics for continuous sensing of local hemoglobin dynamics and (ii) advanced designs in continuous, wireless power delivery and data output for tether-free operation. These features support in vivo, highly localized tissue oximetry at sites of interest, including deep brain regions of mice, on untethered, awake animal models. The results create many opportunities for studying various O2-mediated processes in naturally behaving subjects, with implications in biomedical research and clinical practice.

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Sex Differences in Animal Models of Traumatic Brain Injury

Journal of Experimental Neuroscience ◽

10.1177/1179069519844020 ◽

2019 ◽

Vol 13 ◽

pp. 117906951984402 ◽

Cited By ~ 9

Author(s):

Todd G Rubin ◽

Michael L Lipton

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Animal Models ◽

Enhanced Recovery ◽

Behavioral Outcomes ◽

Epidemiologic Studies ◽

Adequate Treatment ◽

Heterogeneous Nature ◽

Models Of Injury ◽

Underlying Mechanisms

Traumatic brain injury (TBI) is highly prevalent and there is currently no adequate treatment. Understanding the underlying mechanisms governing TBI and recovery remains an elusive goal. The heterogeneous nature of injury and individual’s response to injury have made understanding risk and susceptibility to TBI of great importance. Epidemiologic studies have provided evidence of sex-dependent differences following TBI. However, preclinical models of injury have largely focused on adult male animals. Here, we review 50 studies that have investigated TBI in both sexes using animal models. Results from these studies are highly variable and model dependent, but largely show females to have a protective advantage in behavioral outcomes and pathology following TBI. Further research of both sexes using newer models that better recapitulate mild and repetitive TBI is needed to characterize the nature of sex-dependent injury and recovery, and ultimately identifies targets for enhanced recovery.

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A novel computational sheep atria model for the study of atrial fibrillation

Interface Focus ◽

10.1098/rsfs.2012.0067 ◽

2013 ◽

Vol 3 (2) ◽

pp. 20120067 ◽

Cited By ~ 20

Author(s):

Timothy D. Butters ◽

Oleg V. Aslanidi ◽

Jichao Zhao ◽

Bruce Smaill ◽

Henggui Zhang

Keyword(s):

Atrial Fibrillation ◽

Animal Models ◽

Pulmonary Veins ◽

Experimental Studies ◽

Three Dimensional ◽

Cell Types ◽

Underlying Mechanisms ◽

Detailed Computer ◽

Atrial Cell ◽

Atrial Excitation

Sheep are often used as animal models for experimental studies into the underlying mechanisms of cardiac arrhythmias. Previous studies have shown that biophysically detailed computer models of the heart provide a powerful alternative to experimental animal models for underpinning such mechanisms. In this study, we have developed a family of mathematical models for the electrical action potentials of various sheep atrial cell types. The developed cell models were then incorporated into a three-dimensional anatomical model of the sheep atria, which was recently reconstructed and segmented based on anatomical features within different regions. This created a novel biophysically detailed computational model of the three-dimensional sheep atria. Using the model, we then investigated the mechanisms by which paroxysmal rapid focal activity in the pulmonary veins can transit to sustained atrial fibrillation. It was found that the anisotropic property of the atria arising from the fibre structure plays an important role in facilitating the development of fibrillatory atrial excitation waves, and the electrical heterogeneity plays an important role in its initiation.

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Small animal models of heart failure

Cardiovascular Research ◽

10.1093/cvr/cvz161 ◽

2019 ◽

Vol 115 (13) ◽

pp. 1838-1849 ◽

Cited By ~ 21

Author(s):

Christian Riehle ◽

Johann Bauersachs

Keyword(s):

Heart Failure ◽

Animal Models ◽

Surgical Techniques ◽

Treatment Strategies ◽

Small Animal ◽

Therapeutic Strategies ◽

Genetic Modifications ◽

Small Animal Models ◽

New Treatment ◽

Underlying Mechanisms

Abstract Heart disease is a major cause of death worldwide with increasing prevalence, which urges the development of new therapeutic strategies. Over the last few decades, numerous small animal models have been generated to mimic various pathomechanisms contributing to heart failure (HF). Despite some limitations, these animal models have greatly advanced our understanding of the pathogenesis of the different aetiologies of HF and paved the way to understanding the underlying mechanisms and development of successful treatments. These models utilize surgical techniques, genetic modifications, and pharmacological approaches. The present review discusses the strengths and limitations of commonly used small animal HF models, which continue to provide crucial insight and facilitate the development of new treatment strategies for patients with HF.

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Progress in solving the sex hormone paradox in pulmonary hypertension

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00337.2013 ◽

2014 ◽

Vol 307 (1) ◽

pp. L7-L26 ◽

Cited By ~ 71

Author(s):

Tim Lahm ◽

Rubin M. Tuder ◽

Irina Petrache

Keyword(s):

Animal Models ◽

Sex Hormones ◽

Sex Hormone ◽

Future Research ◽

Estrogen Metabolism ◽

Hormone Synthesis ◽

17Β Estradiol ◽

Pulmonary Arterial ◽

And Gender ◽

Underlying Mechanisms

Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with marked morbidity and mortality. Even though being female represents one of the most powerful risk factors for PAH, multiple questions about the underlying mechanisms remain, and two “estrogen paradoxes” in PAH exist. First, it is puzzling why estrogens have been found to be protective in various animal models of PAH, whereas PAH registries uniformly demonstrate a female susceptibility to the disease. Second, despite the pronounced tendency for the disease to develop in women, female PAH patients exhibit better survival than men. Recent mechanistic studies in classical and in novel animal models of PAH, as well as recent studies in PAH patients, have significantly advanced the field. In particular, it is now accepted that estrogen metabolism and receptor signaling, as well as estrogen interactions with key pathways in PAH development, appear to be potent disease modifiers. A better understanding of these interactions may lead to novel PAH therapies. It is the purpose of this review to 1) review sex hormone synthesis, metabolism, and receptor physiology; 2) assess the context in which sex hormones affect PAH pathogenesis; 3) provide a potential explanation for the observed estrogen paradoxes and gender differences in PAH; and 4) identify knowledge gaps and future research opportunities. Because the majority of published studies investigated 17β-estradiol and/or its metabolites, this review will primarily focus on pulmonary vascular and right ventricular effects of estrogens. Data for other sex hormones will be discussed very briefly.

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Underlying Mechanisms of Anti-spasmodic, Antidiarrheal, Antioxidant and Acute Toxicity Assessments of Aqueous Extract of Mentha Suaveolens Ehrh and its Fourier Transform Infra-red Spectroscopy Analysis

European Journal of Medicinal Plants ◽

10.9734/ejmp/2020/v31i1830342 ◽

2020 ◽

pp. 37-54

Author(s):

EL-Akhal Jamila ◽

Chda Alae ◽

Tazi Abdelali ◽

Boukir Abdelatif ◽

Bencheikh Rachid

Keyword(s):

Fourier Transform ◽

Animal Models ◽

Functional Groups ◽

Aqueous Extract ◽

Castor Oil ◽

Butylated Hydroxytoluene ◽

Calcium Antagonism ◽

Small Intestinal Transit ◽

Infra Red ◽

Underlying Mechanisms

Objective: The aim of this present study is to investigate the antidiarrheal, spasmolytic and antioxidant activities of aqueous extract of Mentha suaveolens Ehrh (AEMS), to study their underlying mechanisms in animal models and to reveal its main functional groups using Fourier Transform Infra-Red Spectroscopy (FTIR). Methods: Mentha suaveolens Ehrh was studied for antidiarrheal activity on Wistar rats of both sexes at the doses of 200 and 800 mg/kg body weight using castor oil-induced diarrhea, castor oil-induced enteropooling and small intestinal transit models. The extract was studied for antispasmodic property in isolated rabbit jejunum using various spasmogenic agents including Ach (10-5M), KCl (100 mM) and in the absence and in the presence of L-NAME (10-4 M) and the methylene blue (10-5 M).The antioxidant capacity of AEMS was carried out using DPPH radical scavenging activity and the ferric reducing antioxidant potential (FRAP). Ascorbic acid and Butylated HydroxyToluene (BHT) were used as references. The functional chemical groups were determined by FTIR. Results: The great antidiarrheal potential of AEMS seems to be mediated through calcium antagonism. The marked and concentration-dependent induced spasmolytic effect of AEMS appears to involve Ca2+ voltage channel blockade and the NO/cGMP pathway activation. AEMS possessed strong and concentration-dependent antioxidant potency using DPPH and FRAP. Polyphenols, carboxyl and carbohydrates were found to be the main functional groups in the AEMS analyzed by FTIR. Conclusion: Overall, our current findings provide scientific proves in animal models for the traditional use of AEMS in folk medicine for the prevention or the treatment of gastrointestinal diseases in Morocco.

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Challenges and future perspectives for 3D cerebral organoids as a model for complex brain disorders

Neuroscience Research Notes ◽

10.31117/neuroscirn.v2i1.28 ◽

2019 ◽

Vol 2 (1) ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Pike-See Cheah ◽

John O. Mason ◽

King Hwa Ling

Keyword(s):

Bipolar Disorder ◽

Animal Models ◽

Human Brain ◽

Neurodegenerative Disorders ◽

Neural Circuitry ◽

Brain Diseases ◽

Brain Disorders ◽

Future Perspectives ◽

Human Material ◽

Underlying Mechanisms

The human brain is made up of billions of neurons and glial cells which are interconnected and organized into specific patterns of neural circuitry, and hence is arguably the most sophisticated organ in human, both structurally and functionally. Studying the underlying mechanisms responsible for neurological or neurodegenerative disorders and the developmental basis of complex brain diseases such as autism, schizophrenia, bipolar disorder, Alzheimer’s and Parkinson’s disease has proven challenging due to practical and ethical limitations on experiments with human material and the limitations of existing biological/animal models. Recently, cerebral organoids have been proposed as a promising and revolutionary model for understanding complex brain disorders and preclinical drug screening.

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