Stroke is a leading cause of death and disability worldwide. Effective
intervention for acute stroke remains to be a significant unmet medical need. In the past
several decades, a large number of therapeutic-pharmacological agents have been evaluated
in preclinical models with many advancing to late stages of clinical study. However, all
potential interventions (with the exception of the approval of early thrombolysis using
recombinant tissue plasminogen activator; tPA) have failed. To address this translational
gap, a series of meetings by the Stroke Therapy Academic Industry Roundtable (STAIR)
has conducted and has made recommendations over the past decade in order to provide
guidance to the stroke research community in the development of novel stroke therapeutic
interventions. In spite of these efforts, large clinical studies have continued to fail. This
chapter describes the most commonly used preclinical stroke models that have been applied
to novel drug discovery, including critiques and translational perspectives of their
advantages and limitations. Furthermore, novel biomarkers are used in stroke intervention
research, including the monitoring of salvageable brain tissue as a therapeutic index of
potential protection. For example, the measurement of the ischemic penumbra is discussed
as an important means to more accurately assess and translate the efficacy of therapeutic
agents from animal models to man.
Keywords: Animal model, biomarker, brain ischemia, drug development, drug
discovery, MCAO, penumbra, rat, stroke, translational medicine, translational
model.
