A novel calpastatin-based inhibitor improves postischemic neurological recovery.
Journal - Biochemical and biophysical research communications (United States )
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.
|ISSN : ||1090-2104|
|Mesh Heading : ||Animals Blood-Brain Barrier Brain Calcium-Binding Proteins Calpain Cerebral Infarction Cysteine Proteinase Inhibitors Disease Models, Animal Male Peptide Fragments Rats Rats, Wistar Spectrin metabolism physiopathology administration & dosage therapeutic use administration & dosage antagonists & inhibitors metabolism physiopathology administration & dosage metabolism administration & dosage metabolism metabolism|
|Mesh Heading Relevant : ||drug effects therapeutic use drug therapy therapeutic use therapeutic use|