Overcoming barriers to translation from experimental stroke models

Abstract

The current understanding of stroke pathophysiology and the recognition of advantages and disadvantages of animal models are providing a renewed incentive for translational research. However, when neuroprotective drugs that work in animal models for adult stroke fail when tested in humans, this can result in major setbacks for developing stroke therapy. In this review, we will define key challenges and complexities in translational stroke research. In part 1, we focus on how to choose an appropriate experimental stroke model, role of species, strain, sex and age of animals, morphological and functional differences between the brain of humans and animals, and protection of cerebral gray matter (instead of both gray and white matter). In part 2, we discuss preclinical pitfalls, including physiological monitoring, role of anesthesia, dosing and side effects, therapeutic window, and outcome measures. In part 3, we focus on the ischemic penumbra as a target of neuroprotection in experimental and clinical stroke. By recognizing the advances in stroke basic science, translational research is moving forward in the development of new effective acute stroke treatments. Success in this endeavor requires increased interactions and cooperation between basic scientists and clinical researchers.