Secreted Protein Acidic and Cysteine Rich (SPARC) Regulates the Pathological Response to Ischemic Insults and Represents a Promising Therapeutic Target for Stroke Treatment

Abstract

Secreted protein acidic and cysteine rich (SPARC) is a nonstructural, multifunctional matricellular protein involved in tissue development, extracellular matrix, and immune response. In this study, by using mice deficient in SPARC, the role of SPARC in the pathogenesis of ischemic stroke is characterized. It is found that, compared to the wild‐type mice, SPARC deficient mice demonstrated 48.3% reduction in cerebral infarction after ischemia insult. Mechanistically, it is shown that SPARC deficiency significantly reduces ischemia induced cellular apoptosis, diminishes inflammatory response in the ischemic area as well as in the circulatory system, and enhances the integrity of the blood–brain barrier. It is further assessed if SPARC could be targeted for stroke treatment through intraventricular or intravenous administration of SPARC neutralizing antibody. It is found that delivery of SPARC antibody through either route effectively reduces ischemia‐induced infarction. Taken together, the study suggests that SPARC plays an important role in the pathological response to ischemic insults, and represents a promising therapeutic target for clinical management of stroke.