Zebrafish (Danio rerio) Developed as an Alternative Animal Model for Focal Ischemic Stroke

Thrombotic cerebral ischemia is one of the leading causes of mortality and chronic disability. Animal models provide an essential tool for understanding the complex cellular and molecular pathophysiology of ischemia and for improving treatment and testing novel neuroprotective drugs in the preclinical setting. In this study, we tested zebrafish as a novel model for thrombotic ischemic brain damage. Zebrafish were intraperitoneally injected with Rose Bengal and light exposure was directed onto the optic tectum region of the brain to induce photothrombosis. After full recovery from anesthesia, zebrafish consistently exhibited abnormal swimming patterns, indicating brain injury from the procedure. The staining of 2,3,5-triphenyltetrazolium chloride (TTC) 24 h after the treatment showed lack of staining of the exposed area of the brain, which further confirmed the ischemic injury. Application of Activase®-tPA improved viability of the brain. The tPA treatment also reduced the occurrence of moving disability as well as the mortality rate, demonstrating that the zebrafish model not only showed focal ischemic injury but also responded well to tPA therapy. Our results suggest that the current photothrombotic method induced focal ischemia in zebrafish and produced consistent brain damage that can be measured by behavioral changes and quantified by histological staining.