A novel calpastatin-based inhibitor improves postischemic neurological recovery

• Published in: Biochemical and biophysical research communications 2009-07, Vol.385 (1), p.94-99
• Main Authors: Anagli, John, Han, Yuxia, Stewart, Laura, Yang, Dongmei, Movsisyan, Ashkhen, Abounit, Kadija, Seyfried, Donald
• Format: Article
• Language: English
• Subjects: Animals; Blood-Brain Barrier - metabolism; Brain - drug effects; Brain - physiopathology; Calcium-Binding Proteins - administration & dosage; Calcium-Binding Proteins - therapeutic use; Calpain; Calpain - administration & dosage; Calpain - antagonists & inhibitors; Calpain - metabolism; Calpain - therapeutic use; Calpastatin; Cerebral Infarction - drug therapy; Cerebral Infarction - physiopathology; Cysteine Proteinase Inhibitors - administration & dosage; Cysteine Proteinase Inhibitors - metabolism; Cysteine Proteinase Inhibitors - therapeutic use; Disease Models, Animal; Male; Middle cerebral artery occlusion; Neurological recovery; Peptide Fragments - administration & dosage; Peptide Fragments - metabolism; Peptide Fragments - therapeutic use; Protease inhibitor; Rat; Rats; Rats, Wistar; Spectrin - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2009.04.141

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.