Cardiac glycosides provide neuroprotection against ischemic stroke: discovery by a brain slice-based compound screening platform.

ABSTRACT: We report here the results of a chemical genetic screen using small molecules with known pharmacologies coupled with a cortical brain slice-based model for ischemic stroke. We identified a small-molecule compound not previously appreciated to have neuroprotective action in ischemic stroke, the cardiac glycoside neriifolin, and demonstrated that its properties in the brain slice assay included delayed therapeutic potential exceeding 6 h. Neriifolin is structurally related to the digitalis class of cardiac glycosides, and its putative target is the Na(+)/K(+)-ATPase. Other cardiac glycoside compounds tested also showed neuroprotective activity, although with lower apparent potencies. In subsequent whole-animal studies, we found that neriifolin provided significant neuroprotection in a neonat

SUBMITTER: Wang JKT 

PROVIDER: S-EPMC1481664 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature