Global Ischemic Four-Vessel Occlusion (4-VO) Rat Model

Global cerebral ischemia resulting from cardiac arrest, stroke, and hypoxia is a problem of increasing clinical significance. Here at Creative Biolabs, we offer a four-vessel occlusion rat model of global ischemia for our clients to study the unusual pattern of delayed neuronal cell death observed after global ischemia and to test drugs for neuroprotective activity. Our comprehensive experience and expertise, coupled with a set of behavioral and analytical tests have allowed us to provide reliable and high-quality data.

Induction of 4-VO Rat Model

Four-vessel occlusion (4-VO) rat model has been widely employed to investigate the mechanisms underlying brain damage after transient global ischemia, which mimic the pathological conditions of cardiac arrest. 4-VO is produced by permanent coagulation of two vertebral arteries and temporary ligation of two common carotid arteries. This model induces transient forebrain ischemia because the blood supply to the hindbrain remains relatively intact. Such insults cause severe, reversible forebrain ischemia with consistent neuronal damage in rat species that are large enough to allow physiological monitoring and maintenance with relatively low costs.

The original model involves a 2-day procedure inducing an ischemic insult in awake animals. Modifications are made to this model by investigators, such as the use of anesthetized animals. The use of anesthesia provides the opportunity to evaluate physiological parameters during the ischemic period and drug administration but eliminates the possibility of assessing the degree of ischemia by examining neurological signs. The use of the unanesthetized rat probably provides a more realistic, physiologically relevant model of global forebrain ischemia. However, the anesthetized preparation provides more of an opportunity to utilize the more invasive methods for the study of ischemic and postischemic pathophysiological changes. Creative Biolabs conducts the preclinical therapeutic evaluation of putative drugs in the anesthetized rat model.

Features of 4-VO Rat Model

• Four-vessel occlusion model in the rat induces transient forebrain ischemia that resembles cardiac arrest in clinical situations.
• In the 4-VO model, there is selective neuronal death. The astrocytes undergo hypertrophy and the microglia become activated. There is no infiltration of peripheral immune cells into the brain parenchyma. Neuronal cell death is delayed and matures over a period of 24 hours to 7 days.
• The 4-VO model is a useful model to study the unusual pattern of delayed neuronal cell death observed after global ischemia, and also it can be used as a model to test drugs for neuroprotective activity.

Assessments

For the study of potential neuroprotective and therapeutic agents of stroke, our neurological disease research platform offers an array of behavioral tests, behavioral recuperation tests, and histological assessments, including but not limited to:

• Behavioral tests (e.g., motor function, cognition, social behavior)
• Cerebral blood-flow and vessels imaging (transcranial laser Doppler)
• Infarct volume measurement (magnetic resonance imaging (MRI), tetrazolium chloride (TTC))
• Histology (H&E staining of brain tissue)

Creative Biolabs also offers other stroke & brain ischemia rodent models that you may be interested in:

• Middle Cerebral Artery Occlusion (MCAO) Rodent Model
• Endothelin-1 Model
• Photothrombotic Ischemia Model

The following list covers the extensive range of rodent neurological disease models available at Creative Biolabs:

Please contact us to discuss your requirements and we can work with you to customize a detailed study plan that fits your exact needs.

For Research Use Only.