A novel calpastatin-based inhibitor improves postischemic neurological recovery.

Department of Pathology, Henry Ford Hospital, 1 Ford Place, 5D, Detroit, MI 48202, USA.
Biochemical and Biophysical Research Communications (Impact Factor: 2.28). 06/2009; 385(1):94-9. DOI: 10.1016/j.bbrc.2009.04.141
Source: PubMed

ABSTRACT Calpastatin, a naturally occurring protein, is the only inhibitor that is specific for calpain. A novel blood-brain barrier (BBB)-permeant calpastatin-based calpain inhibitor, named B27-HYD, was developed and used to assess calpain's contribution to neurological dysfunction after stroke in rats. Postischemic administration of B27-HYD reduced infarct volume and neurological deficits by 35% and 44%, respectively, compared to untreated animals. We also show that the pharmacologic intervention has engaged the intended biologic target. Our data further demonstrates the potential utility of SBDP145, a signature biomarker of acute brain injury, in evaluating possible mechanisms of calpain in the pathogenesis of stroke and as an adjunct in guiding therapeutic decision making.

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