Rodent models of global cerebral ischemia: a comparison of two-vessel occlusion and four-vessel occlusion.

1. Human stroke is a complex and heterogeneous phenomenon that may defy attempts to develop a unitary animal model with which to address all of the relevant issues. 2. Focal models are regarded by many to be the approach of choice, but both global and focal models of cerebral ischemia can be sources of useful and complementary insight. 3. Of the global models, four-vessel occlusion requires a preparatory operative procedure that may increase the risk of extraneous factors confounding the response to the ischemic insult itself. The procedures are only partly reversible, with the vertebral arteries remaining permanently occluded. 4. The two-vessel occlusion model is easier to perform in a single procedure, and the less-intrusive surgical intervention allows greater scope for recovery experiments. The occlusion is fully reversible. 5. Many classes of compounds with therapeutic potential have been identified in the laboratory, often on the basis of success in one class of animal model, but translating these successes into a clinical context has proved singularly difficult. If, in future, compounds of interest are tested across a range of the available models, the likelihood of subsequent clinical success may be enhanced.