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ThrombosisHypertensionWound HealingRadiation Countermeasures - Acute Radiation Syndrome (ARS)Parkinson’s DiseaseAutism Spectrum DisorderDepression
Neuroscience and Additional ModelsBioModels offers customized solutions by working with clients to develop novel models for disease areas that may not be readily or easily standardized in the field. Furthermore, models are sometimes necessary for areas in biological research that are a bit less mainstream, representing niche areas of inquiry. At BioModels, requests from clients for custom models have been translated into the development of tested and validated models including thrombosis and blood pressure monitoring.
Assess your novel therapeutics for efficacy and mechanism of action in BioModels’ established thrombosis models. Thrombosis, the formation of a clot inside a blood vessel, can have devastating consequences, including death. BioModels’ thrombosis models allow you to evaluate blood clot formation in blood vessels. The BioModels team is experienced with a venous and arterial thrombosis models which are available with diverse experimental endpoints, such as:
Assess your novel therapeutics for efficacy and mechanism of action in BioModels’ established hypertension models. Hypertension, or high blood pressure, affects approximately 25% of the adult population in the United States. Left untreated, hypertension can lead to a number of health problems, such as heart disease, heart attack, and stroke. BioModels’ hypertension models allow you to evaluate high blood pressure by monitoring systolic and diastolic pressures. The BioModels team is experienced with spontaneous and diet-induced hypertension models which are available with diverse experimental endpoints, such as:
Assess your novel therapeutics for efficacy in BioModels’ established wound healing models. Chronic nonhealing wounds are correlated with diseases such as diabetes, hypertension, chronic kidney disease and can have huge quality of life effects on patients. BioModels’ wound healing models allow you to evaluate the complex biological processes associated with healing and repair. The BioModels team is experienced with splinted wound healing model which is available with diverse experimental endpoints, such as:
At BioModels, you can assess your novel therapeutics for efficacy and mechanism of action in our established models of Acute Radiation Syndrome (ARS) to address unmet clinical needs for patients. ARS refers to an acute illness caused by exposure to a high dose of penetrating radiation to the body which can affect three distinct areas of the body, the bone marrow, the gastrointestinal tract (GI-ARS), and the cardiovascular/central nervous system (CNS). We offer well-established mouse models of both total body irradiation (TBI) and gastrointestinal tract-focused toxicity through shielding of the long bones to assess critical disease mechanisms and phenotypes. Our literature-validated experimental endpoints include:
Assess your experimental materials for efficacy and mechanism of action in BioModels’ established Parkinson’s Disease model. Parkinson’s disease is a neurodegenerative disorder that results in motor dysfunction. BioModels’ Parkinson’s Disease model captures a spectrum of disease phenotypes, including behavioral and histological endpoints. We offer diverse experimental endpoints, such as:
Assess your novel therapeutics for efficacy in BioModels’ established autism spectrum disorder model. Autism is characterized by impairments in social and communication skills and is diagnosed early in childhood development. BioModels’ autism model allows you to evaluate deficits in social behaviors including social approach, social interaction and abnormal ultrasonic vocalizations. The BioModels team is experienced with the BTBR autism model which is available with experimental endpoints, such as:
Assess your novel therapeutics for efficacy in BioModels’ established depression models. Major depression is a debilitating mental illness, symptoms can include listlessness, feeling hopeless, thoughts of death or suicide, and anhedonia. BioModels’ depression models allow you to screen potential antidepressant therapies. The BioModels team is experienced with the forced swim test and tail suspension test which are available with experimental endpoints, such as:
Study Models
The venous thrombosis model can be used to evaluate the impact of anti-coagulants and has been used to evaluate the potential for compounds to increase the propensity for clot formation. In rodents, thrombus is induced by the direct application of a solution of ferric chloride (FeCl3) to the adventitial surface of the femoral vein. Thrombus formation is measured using intravital video microscopy alone or in combination with a laser Doppler flow probe to monitor vessel occlusion. In addition to the primary endpoint of time to complete occlusion, other flow parameters, including a visual evaluation of blood flow using the Thrombolysis in Myocardial Infarction (TIMI) scoring scale, are assessed. In mice, test article responses can be compared to the effects of Lovenox (Enoxaparin sodium).
Laser Doppler flow monitor which utilizes non-invasive surface probes is used to measure femoral vein blood flow in thrombosis-induced animals.
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The arterial thrombosis model can be used to compare the anti-thrombogenic activities of novel therapeutics to provide a pre-clinical means of assessing the potential benefits of new drugs and drug combinations in reducing the risk of arterial thrombosis. In rodents, thrombus is induced by the direct application of a solution of ferric chloride (FeCl3) to the adventitial surface of the carotid artery. Thrombus formation is measured using intravital video microscopy alone or in combination with a laser Doppler flow probe to monitor vessel occlusion. In addition to the primary endpoint of time to complete occlusion, other flow parameters, including a visual evaluation of blood flow using the Thrombolysis in Myocardial Infarction (TIMI) scoring scale, are assessed.
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Study Models
The spontaneous hypertension model can be used to evaluate the potential benefits of novel therapeutics, and drug combinations in reducing high blood pressure. Spontaneous hypertension is modeled using rodents that have a genetic predisposition to developing hypertension. Non-invasive blood pressure monitoring is employed to evaluate systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate.
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The diet-induced hypertension model can also be used to evaluate the potential benefits of novel therapeutics, and drug combinations in reducing high blood pressure. Hypertension is induced in Dahl-Salt Sensitive rats by a high salt diet. High blood pressure is observed from approximately 1 week on high salt diet. Non-invasive blood pressure monitoring is employed to evaluate systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate.
Blood pressure is monitored twice a week in Dahl-Salt sensitive rats using a non-invasive blood pressure system to measure mean arterial blood pressure (top), systolic blood pressure (middle) and diastolic blood pressure (bottom).
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Study Models
Wound healing can be modeled using normal animals or diabetic animals that have a predisposition for impaired wound healing. After being anesthetized, animals have a full-thickness area of skin removed from the center of the back. Animals are evaluated daily for weight change and three times a week for wound healing progression. Wounds can either be splinted, which prevents wound closure by skin contraction and thus allowing wounds to heal through granulation and re-epithelialization, a process similar to that in humans, or be left to heal with contraction allowed to contribute to the wound healing process.
Animals are weighed daily, and body weight change as compared to Day 0 is calculated. The AUC is calculated to compare treatment groups and is shown in the inset. (**** p<0.0001; compared to db/db group)
Wound length and width is measured 3x/week from Day 0 until end of the study. The AUC is calculated to compare treatment groups and is shown in the inset. (*** p<0.001; compared to db/db group)
Blood glucose levels are measured on Day -1 and at sacrifice on Day 28. (**** p<0.0001; compared to db/db group)
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Study Models
There is a critical need to develop therapies to prevent radiation exposure related deaths resulting from gastrointestinal and bone marrow toxicities. Currently, only potassium iodide is recognized as a radio-protectant in this context, protecting only the thyroid from ingested radioactive iodine. At BioModels, evaluate your test compounds for efficacy in targeting the GI tract, the bone marrow, or both in our mouse model of total body irradiation. Non-anesthetized animals are placed in a pie-shaped multi-chamber plastic restrainer and placed inside the radiation source. A single, precise dose of total body irradiation (x-ray) at varying levels is administered to groups of mice to generate a dose response curve. The radiation dose can be titrated to achieve the lethal dose appropriate for your study. The main endpoints of the model include survival and body weight change. Histological endpoints can also be examined to address the mechanism of action.
C57Bl/6 animals that receive TBI (x-ray) are weighed daily, and body weight change as compared to Day 0 are calculated and shown over the course of the study for each radiation (x-ray) dose level.
Survival of C57Bl/6 mice that receive TBI (x-ray) is tracked daily over the course of the study.
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Exposure to high levels of ionizing radiation results in toxicities of the gastrointestinal (GI) tract that often lead to death. There is a critical need to develop therapies that treat the damaged GI tract to reduce or prevent exposure-related deaths. At BioModels, evaluate your test compounds for efficacy in targeting the GI tract in our validated mouse model of GI-directed acute radiation syndrome. In this model, one hind limb of an anesthetized animal is protected using a lead shield while a single, precise dose of total body irradiation (x-ray) is delivered. The main endpoints of the model include survival and body weight change. Histological endpoints can also be examined to address the mechanism of action.
C57Bl/6 animals that receive TBI with long bone protection are weighed daily, and body weight change as compared to Day 0 are calculated and shown over the course of the study for each radiation (x-ray) dose level.
Survival of C57Bl/6 mice that receive TBI (x-ray) with long bone protection is tracked daily over the course of the study.
C57Bl/6 mice receive TBI (x-ray) with long bone protection. Representative images show the epithelial architecture of the villi and crypts of normal jejunum (A) and damaged jejunum (B) 4 days after exposure to radiation.
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Study Models
The MPTP model of Parkinson’s Disease is among the most widely used in the indication. Pathologically, it presents with dopaminergic neuron loss in the substantia nigra with associated depletion of striatal neuron terminals/dopamine levels. Additionally, the model may present with some behavioral deficits. Rotarod trials are employed to evaluate motor dysfunction; diseased animals demonstrate reduced latencies to fall from the rod.
Animals are evaluated for motor dysfunction via rotarod assessment.
Samples are assessed for dopaminergic neuron loss by tyrosine hydroxylase staining of the substantia nigra.
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Study Models
Autism spectrum disorder is modeled using BTBR mice which display several symptoms of autism including reduced social interactions, and abnormal vocalizations. These unique behavioral phenotypes of the BTBR mouse represent possible analogs to social and communication deficits presented in the human condition. BioModels has validated an index of sociability in BTBR mice using the three chambered social approach test. This model is well-published and translatable to social and communication deficits presented in the human condition.
Mice are free to explore 3 chambers: one with a confined mouse (stranger), one with a novel object (center), and one empty, as a measure of social preference. (** p<0.01, **** p<0.0001; compared to stranger)
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Study Models
The forced swim test, also known as the Porsolt test, is a well-published and widely used method for screening antidepressant compounds. In this model, rodents are placed in a cylindrical tank filled with water and the time spent immobile versus struggling is measured. Immobility is thought to be an index of a depressive-like state which can be reduced by antidepressant treatment.
Mice or rats are placed in an inescapable chamber filled with water and time spent immobile is measured. (**p<0.01; compared to saline)
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The tail suspension test is similar to the forced swim test, but instead of using water, rodents are hung by their tails. The time spent immobile is measured as an index of a depressive-like state which can be reduced by antidepressant treatment.
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