Over decades, all attempts to translate
acute stroke neuroprotectants from discovery in lower-order species to human clinical use have failed. This raised concerns about the predictive validity of preclinical studies in animals for outcomes in human
stroke trials. To bridge this translational gap, we used high-order gyrencephalic nonhuman primates subjected to an experimental protocol that mimicked that of a corresponding, separately reported, clinical trial in which the human subjects underwent endovascular
cerebral aneurysm repair. Both placebo-controlled studies tested neuroprotection by
Tat-NR2B9c, a prospective therapeutic compound, in anesthetized subjects.
Embolic strokes were produced by small intra-arterial emboli caused by the
endovascular procedure. We show that primates treated with
Tat-NR2B9c after the onset of
embolic strokes exhibited significantly reduced numbers and volumes of
strokes, as visualized by diffusion- and T2-weighted magnetic resonance imaging. These results correctly anticipated the outcome of the corresponding human trial, thus validating this study design as a predictor of neuroprotective efficacy in humans. This strategy may facilitate the evaluation of promising
neuroprotectants before undertaking similar studies in human subjects.