Custom Two-Vessel Occlusion (2-VO) Model of Global Ischemic Stroke

Among animal models of global cerebral ischemia stroke, the rat two-vessel occlusion (2-VO) and 4-vessel occlusion (4-VO) models are the most commonly used models to study the molecular mechanisms of neuronal damage after cerebral ischemia-reperfusion. The 2-VO model produced lesions similar in size and location to the 4-VO model, with the exception of the brainstem. In the 2-VO model, bilateral common carotid artery (CCA) occlusion combined with systemic hypotension (50 mmHg) sufficient to induce cerebral ischemia produces reversible forebrain ischemia. This ischemia-reperfusion model affects extensive regions of the forebrain. Compared with the 4-VO model, the 2-VO model is a one-stage surgical procedure, has the advantages of controlled recirculation and lower mortality. The success of the model requires appropriate strain and precise timing of ischemia.

Fig. 1. Experimental timeline of 2-VO global ischemic stroke modeling in rats. (Sanderson et al., 2013)

Custom 2-VO Model

Ace Therapeutics provides customized 2-VO global ischemic animal models for customers worldwide to support basic research and drug development efforts in ischemic stroke, such as molecular, biochemical, and physiological studies, as well as evaluation of neuroprotective drugs. All studies can be customized and adapted to meet customer needs.

Animal Modeling Method

Ace Therapeutics can construct a 2-VO global cerebral ischemia stroke model in lightly anesthetized gerbils and spontaneously hypertensive rats. During ischemia, blood is drawn from the jugular vein or femoral artery, and the bilateral common carotid arteries are immediately blocked to reduce the mean arterial blood pressure (MABP) to 30 mmHg causing cerebral ischemia to the extent of causing neuronal damage. At the end of the ischemic period, the withdrawn blood was returned to the animal.

Our researchers ensure the reliability of this model through precise control of systemic blood pressure during applied hypotension, ischemia duration, tight temperature control, specific anesthesia protocols, and diligent postoperative care.

Animal Model Characterization and Validation

After modeling, we scored the animal models, and Longa scores of 2 to 3 were considered to meet the requirements for experimental studies. Our stroke research platform offers a range of tests to detail expected outcomes on the 2-VO global cerebral ischemia stroke model, including but not limited to:

• Infarct volume measurement (2,3,4-triphenyl tetrazolium chloride (TTC))
• Histology (H&E staining of brain tissue, mainly hippocampal CA1 pyramidal neurons, small to medium-sized neurons in the dorsal and ventral striatum, and pyramidal neurons in layers 3-4 of the neocortex.)
• Behavioral tests (e.g., motor function, cognition, social behavior)
• Cerebral blood-flow and vessels imaging (transcranial laser doppler)
• Quantification of brain damage (counting and quantifying surviving neurons)

Advantages of Our Custom 2-VO Model

• Our 2-VO model is simple to construct and has a low mortality rate, which improves the efficiency of experimental protocols.
• Our 2-VO model is particularly well suited for long-term survival learning studies, providing researchers with the opportunity to explore the lasting effects of ischemic events on cognitive function over a longer period of time.
• With our ability to precisely regulate the reperfusion process in the 2-VO model, researchers can study the specific effects of ischemia and subsequent reperfusion on a variety of physiological and pathological processes.
• The reproducibility of ischemic histopathological injury in our 2-VO model can reach more than 90%, enhancing the reliability of experimental results.

Applications of 2-VO Model

• Study the mechanism of ischemic stroke
• Evaluate ischemic stroke drug efficacy

Ace Therapeutics guarantees quality data for customizable 2-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.

1. Sanderson, T. H., & Wider, J. M. (2013). 2-vessel occlusion/hypotension: a rat model of global brain ischemia. JoVE (Journal of Visualized Experiments), (76), e50173.