A highly reproducible model of cerebral ischemia/reperfusion with extended survival in CB-17 mice

• A highly reproducible cerebral ischemia/reperfusion model with long time survival.
• The most benefit is the reproducibility between animals and laboratories.
• Our preclinical model can provide various pathological conditions.
• It represents a major step forward for testing future therapeutic methods.

To simulate the clinical and pathologic situation in patients with stroke, as well as to evaluate future potential therapeutic approaches, it is essential to have a highly reproducible model that displays long-term survival. Though a range of rodent models has been employed in the literature, there are questions regarding reproducibility, especially in terms of ischemic zone (i.e., degree of ischemia) and long-term survival. We have developed a highly reproducible stroke model that produces a consistent ischemic zone as a result of direct transient occlusion of the middle cerebral artery (MCA) in CB-17 (CB-17/Icr-+/+Jcl) mice. The model employs a thin monofilament to twist the artery resulting in complete interruption of blood flow. Transient ischemia can be induced for up to 240 min and the survival rate at 7 days post-ischemia was more than 60%, even in mice subjected to 240 min of transient ischemia resulting in hemorrhagic infarction in most animals. Our method can be used to model several pathologic conditions, such as reversible reperfusion injury, delayed neuronal death, necrotic brain injury and hemorrhagic infarction. We believe this preclinical model provides a step forward for testing future therapeutic approaches applicable to patients with ischemic brain injury.