EXPERIMENTAL ANIMAL MODELFOR INDUCING DIFFERENT

DISEASE CONDITIONS.Presented by

Dr. Sindhu K.

MVSc Scholar, Dept. of VPT,

COVAS, Pookode.

• An animal with a disease either the

same as or like a disease in humans.

• Animal models are used to study the

development and progression of

diseases and to test new treatments

before they are given to humans.

• Animals with transplanted human

cancers or other tissues are called

xenograft models.

Anti-inflammatory animal models

Anti-pyretic animal models

Anti-arrhythmic animal models

Anti-hypertensive animal models

Anti-hyperglycemic animal models

Anti-cholesteremic animal models

Animal models for CNS activity

Animal models to evaluate Muscle relaxant activity

Model to evaluate CNS depression & sedation

Animal models for anti-anxiety activity

Anti-convulsant & Anti-epileptic animal models

Analgesic animal models

ANTI-INFLAMMATORY MODELS.

• Acute models

• Sub acute models

• Chronic models

• OVA-challenged Mouse Asthma Model

• Acute LPS model

• Chronic LPS Model

• Formalin-induced Chronic Inflammation

For inflammatory

models

Phlogistic agents: Brewer’s yeast,

formaldehyde, dextran, egg albumin, kaolin,

Aerosil®, sulfated polysaccharides like

carrageenan or naphthoylheparamine.

For edema models

Histamine, xylene, arachidonic acid, phorbol myristate acetate, oxozolone,

croton oil and formalin.

I. ACUTE MODELS

• Carrageenan-induced Paw Edema in Rats

• Histamine Induced Paw Edema in Rats

• Acetic Acid-Induced Vascular Permeability

• Xylene Induced Ear Edema (Thickness and weight parameter)

• Arachidonic Acid-Induced Ear Edema

• Phorbol Myristate Acetate-Induced Ear Edema in Mice

• Myeloperoxidase (MPO) Assay

• Oxazolone-induced Ear Edema in Mice

II. SUB-ACUTE MODEL

• Carrageenan Induced Granuloma Pouch Model

• Formalin-induced Paw Edema

III. CHRONIC MODEL

• Cotton Pellet-Induced Granuloma in Rats

• The Glass Rod Granuloma

ANTI-PYRETIC MODELS

BREWERʼS YEAST INDUCED PYREXIA

Animals should be fasted 6 hrs. before the yeast administration.

Basal rectal temperature of animals were measured.

Aqueous 20% w/v of brewer’s yeast in 2% gum acacia @ a dose of 10-

20 mg/kg body weight administered subcutaneous near the

neck/groin of the animals.

Rectal temperature (RT) after 19 hrs.

RT increase in at least 0.6 ̊ c is considered as positive.

RT should be taken after administration of test substance @ 0, 1, 2,

3, 4 & 5 hrs.

Compare with initial temperature.

Plot the Graph.

LIPOPOLYSACCHARIDE INDUCED PYREXIA

Overnight fasting + adlibitum water.

Inject 0.3 μg/kg lipopolysaccharide (LPS) (from E.

coli) i.v. through the marginal ear vein dilated with

xylene.

Immediately after administration of LPS, withdraw

food.

After19 hrs. record rise in rectal temperature.

RT rise in 0.6 ̊ c or more is considered as positive.

Record the RT consecutively for 5 hrs.

Compare recorded with Basal rectal temperatures

(T°C).

Plot the graph.

Anti-arrhythmic

models

Isolated Cells and Cell Cultures

Tissue and Organ Bath Preparations

Langendorff System (Isolated Heart)

Transgenic models

SVT

A regular, abnormally fast heart beat

(tachycardia) caused by rapid firing

of electrical impulses from a focus

above the atrioventricular node (A-V

node) in the heart.

Its called supraventricular because

the tachycardia originates above the

ventricles of the heart.

SUPRAVENTRICULAR TACHYCARDIA MODELS.

Wolf-Parkinson –White syndrome.

Pre excitation in dogs.

Transgenic mouse

(PRKAG2 over expression)

Re-entrant arrhythmia of AV node.

Isolated rabbit heart preparation.

Isolated rabbit heart atrium preparation (AV node + bundle of HIS)

Blockade of atrial impulse from anterior site of AV node in dogs.

Isolated canine AV nodal preparation.

ATRIAL FLUTTER.

• Atrial flutter is an abnormality in

the beating of the heart. Such

abnormalities, whether in the

rhythm or speed of the heartbeat,

are known as arrhythmias.

• Atrial flutter is similar to atrial

fibrillation, a common heart rhythm

disorder.

• The difference between flutter and

fibrillation is that flutter is well

organized while fibrillation is not.

Canine right atrial crush injury model.

Atrial flutter induced by Ach & rapid

patching in the dogs.

Atrial flutter by Aconitine.

Right atrial enlargement model of

atrial flutter.

Atrial flutter

Atrial fibrillation is an

irregular and often rapid

heart rate that commonly

causes poor blood flow to

the body.

During atrial fibrillation,

the heart's two upper

chambers (the atria) beat

chaotically and irregularly

— out of coordination with

the two lower chambers

(the ventricles) of the heart.

ATRIAL FIBRILLATION (AF) MODELS.

AF by atrial ischemia in dogs.

PACAP-27 induced biphasic chronotropiceffect & A.F.

AF in dogs by atrial burst patching.

Vagal AF

AF in isolated Langendorff-perfused rabbit heart.

AF by fibrillation pacemaker.

AF by Aconitine.

canine model of chronic atrial fibrillation.

VENTRICULAR FIBRILLATION MODELS.

VF induced by 60 Hz alternating current in isolated swine right

ventricles.

Ischemia induced ventricular arrhythmia.

Ventricular arrhythmia during exercise by ischemia.

Stretch induced arrhythmias in isolated canine ventricle.

Model for sudden cardiac death.

Canine model of two stage ligation.

ANIMAL MODELS OF HYPERTENSION

Renovascular hypertension

Endocrine hypertension

Psychogenic hypertension

Genetic hypertension

Neurogenic hypertension

Dietary hypertension

ANIMAL MODELS FOR DIABETES MELLITUS

Spontaneous diabetic models

Obese

ob/ob mouse, KK/Ay mouse, NZO mouse, NONcNZO10 mouse, TSOD mouse, M16

mouse.

Zuffer fatty Rat, ZDF rat, SHR/N-cp rat,

JCR/LA-cp rat, OLETF rat, Obese rhesus

monkey.

Non-Obese

Cohen diabetic rat, Torrirat Non obese C57BL/6.

Akita mutant mouse, GK rat.

DIET/NUTRITION INDUCED DIABETIC ANIMALS

C57/BL 6J mouse.

Spiny mouse.

Sand rat.

Chemically induced diabetic animals

Obese

GTG treated obese mice.

Non obese

Low dose ALX or STZ adult

rats, mice, etc.

Surgical diabetic animals

VMH lesioned dietary obese diabetic

animals

Obese Partial pancreatectomized animals e.g. dog, primate, pig & rats.

Non obese

TRANSGENIC/KNOCK-OUT DIABETIC ANIMALS.

• β3 receptor knockout mouse

• Uncoupling protein (UCP1)

• Knock-out mouse model

Obese model

• PPAR-ɣ tissue specific knock out mouse

• Glucokinase or GLUT 2 gene knock out mice.

• Human islet amyloid polypeptide over expressed rat (HIP rat)

Non obese model

ANTI-CHOLESTEREMIC ANIMAL MODEL.

Diet induced hyperlipidemia

(400 mg/kg

cholesterol in 5ml coconut oil)

Animal models to evaluate CNS

activity.

Exploratory behaviour

pattern

Spontaneous motor activity

Forced motor activity

General behavioral

pattern

• General behavioral profiles: Awareness, Alertness, Touch

response, Pain response & Sound response.

• Exploratory behavioral pattern evaluation: Y maze test &

Head dip test.

• Spontaneous motor activity: Photoactameter.

• Forced motor activity (muscle relaxant activity): Rota rod test

& Horizontal wire test.

Animal models for muscle relaxant

activity

Traction test

Rota rod test

300 inclined screen test

Chimney Test

Tail suspension model of hind limb

ANIMAL MODELS FOR CNS DEPRESSION & SEDATIVE ACTIVITY.

CNS depression

models

Model to evaluate sedative activity

Antianxiety models

• CNS depression models: Hole cross test & Open field test.

• Antianxiety models: Elevated plus maze test, Hole board

test & Open field test.

• Model to evaluate sedative activity: Barbiturate induced

sleep model.

ANIMAL MODELS FOR ANTIANXIETY ACTIVITIES.

Elevated plus maze test

Hole board test

Open field test

ANIMAL MODELS FOR EVALUATION OF ANTICONVULSANT ACTIVITY &

ANTIEPILEPTIC DRUGS

Anticonvulsant models.

Seizure models.

• Pentylene tetrazole induced

convulsions

• Maximal electric shock induced

convulsions

• Genetic seizure models

• Photosensitive baboon (Papio papio)• Mongolian gerbils (Meriones

unguiculatus)

ANIMAL MODELS USED IN THE SCREENING OF ANTIEPILEPTIC DRUGS.

• Genetic seizure models

• Several genetic model of epilepsy validated

using clinically effective drugs (Partial-

onset seizures: Kindling, Status

epilepticus, Senegalese baboons (Papio

papio),Generalized seizures)

• Photosensitive baboon (Papio papio)

• Mongolian gerbils (Meriones unguiculatus)

ANALGESIC ACTIVITY

•Tail immersion test

•Tail flick test (Analgesiometer)

REFERENCES.

• Anupama A. Suralkar, Prashant S. Sarda, Mahesh M. Ghaisas, Vishnu N. Thakare, & Dr.

Avinash D. Deshpande. 2012. Lecture notes on inflammation. Dr. D. Y. Patil Institute of

Pharmaceutical Sciences & Research, Pimpri, Pune.

• Bhat L. K., Nandakumar K. and Bhodankar S. L. 2005. Animal models to induce cardiac

arrhythmia. Indian J. Pharmacol. 37(6): 348-357.

• Srinivasan K. & Ramarao P. 2007. Animal models in type 2 diabetes research: An

overview. Indian J Med Res. (1): 451-472.

• Kanakam Vijayabhaskar, Vurugonda Ramadevi, Kalakota Chaitanyaprasad, Sadhiram

Rajeshkumar, Divya Sripada and G. Himabindu. 2014. Evaluation of anti-cholesteremic

and anti-lipidemic activity of seed extract of Achyranthes aspera in diet induced

hyperlipidemia model in rats Journal of Chemical and Pharmaceutical Research.

6(5):1247-1250.

• Google images & Wikipedia.