Custom Four-Vessel Occlusion (4-VO) Model of Global Ischemic Stroke

Global cerebral ischemia stroke is a whole-brain injury caused by cardiac arrest and resuscitation and is characterized by a severe reduction in whole-brain cerebral blood flow. The four-vessel occlusion (4-VO) rat model has been widely used to study the molecular mechanisms underlying the pathophysiology of cardiac arrest-induced global cerebral ischemia. The model is designed to induce systemic ischemia by occluding the four major blood vessels supplying blood to the brain (two vertebral arteries and two common carotid arteries). In this model, "delayed neuronal death" is selectively observed in the CA1 pyramidal layer of the hippocampus, a clinical phenomenon that also occurs in humans; neurodegeneration is not observed until approximately 3 days after 4-VO, but intense degeneration with cognitive deficits occurs after 7 days. The model has several advantages, such as ease of preparation, a high incidence of predictable ischemic neuronal damage, and a low rate of seizures.

Fig. 1. Protocol for establishing a global ischemia model using a 4-vessel occlusion in rats. Fig. 1. Protocol for establishing a global ischemia model using a 4-vessel occlusion in rats. (Kim et al., 2023)

Custom 4-VO Model

Ace Therapeutics provides customized 4-VO global ischemic animal models for customers worldwide to study the complex cellular and molecular pathophysiology of global cerebral ischemia stroke as well as to test novel neuroprotective or anti-inflammatory medications in a preclinical setting. All studies can be customized and adapted to meet customer needs.

Our expertise and extensive experience in ischemic stroke model construction, as well as a range of behavioral and analytical tests on animal models, ensures that we can provide you with reliable and high-quality data.

Animal Modeling Method

Our 4-VO global cerebral ischemia stroke model is produced in anesthetized rats and results in bilateral hemispheric ischemia with highly predictable brain damage.

Stage Ⅰ: Permanent occlusion of vertebral arteries (VAs)	A noninvasive grommet was loosely placed around each common carotid artery and externalized in the animal's neck the day before the experiment. The vertebral artery at the second vertebra was electrocauterized under the microscope to ensure complete occlusion of the circulation in both VAs. Looping of bilateral common carotid arteries (CCAs), immediately after the permanent occlusion of VAs.
StageⅡ: Transient occlusion of CCAs	The next day, when the animal is awake, the common carotid artery is occluded, producing ischemia. This procedure must result in a complete loss of the flip-right reflex in the animal.

Animal Model Characterization and Validation

4-VO models result in delayed and selective neuronal death and cognitive impairment. After modeling, we scored the animal models, and Longa scores of 2 to 3 were considered to meet the requirements for experimental studies. In addition, we provide a series of detailed assessment methods to test the results, including but not limited to:

Advantages of Our Custom 4-VO Model

Allows anesthesia to be applied without compromising the primary selection criteria, which can improve the performance of surgical procedures.
Successfully simulates the main pathological processes of total cerebral ischemia/reperfusion injury without causing visual impairment in rats.
Provides the possibility of invasive physiological monitoring, allowing researchers to obtain real-time data on various physiological changes during ischemic events, including monitoring of parameters such as blood pressure, cerebral blood flow, intracranial pressure, and cerebral metabolism.
High incidence of predictable ischemic neuronal damage. It is a reliable platform to study the mechanisms of brain injury after ischemic stroke.
Post-ischemic seizures can complicate experimental stroke models and introduce confounding variables in data interpretation. Our customized 4-VO model is specifically designed to eliminate post-ischemic seizures.

Applications of 4-VO Model

Study molecular mechanisms underlying the pathophysiology of cardiac arrest-induced global cerebral ischemia in animals
Investigate the mechanisms of selective and delayed neuronal death of hippocampal CA1 neurons and hippocampal-based cognitive deficits
Evaluate neuroprotective drug efficacy of ischemic stroke

Ace Therapeutics guarantees quality data for customizable 4-VO global cerebral ischemia stroke models. With superior solutions and an experienced team, we are your ideal partner for stroke research. Clients can contact us directly and receive timely feedback.

Reference

Kim, H., et al. (2023). Protocol for establishing a global ischemia model using a 4-vessel occlusion in rats. STAR protocols, 4(4), 102630.

All of our services are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.