A novel calpastatin-based inhibitor improves postischemic neurological recovery

作者：Anagli John^*; Han Yuxia; Stewart Laura; Yang Dongmei; Movsisyan Ashkhen; Abounit Kadija; Seyfried Donald

来源：Biochemical and Biophysical Research Communications, 2009, 385(1): 94-99.

DOI：10.1016/j.bbrc.2009.04.141

• Calpain
• Calpastatin
• Middle cerebral artery occlusion
• Neurological recovery
• Protease inhibitor
• Rat

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.

• 出版日期2009-7-17