Cystatin C Is a Crucial Endogenous Protective Determinant Against Stroke

• DOI: 10.1161/strokeaha.116.014975
• Publication Date: 2016-12-21T02:30:20Z
• Authors: Zongping Fang; Jiao Deng; Zhixin Wu; Beibei Dong; Shiquan Wang; Xiaodan Chen; Huang Nie; Hailong Dong; Lize Xiong
• Keywords: Ischemic Preconditioning; Stroke; Knockout mouse

Background and Purpose— Endogenous neuroprotection can be induced by ischemic nonischemic preconditioning. However, not all subjects that undergo preconditioning exhibit similar favorable outcome. This study is to explore the molecules responsible for this phenomenon find new therapeutic targets stroke. Methods— Adult male Sprague–Dawley rats were subjected transient middle cerebral artery occlusion. High-throughput proteomic technique, isobaric tag relative absolute quantification, was used screen differentially expressed proteins in developed tolerance from hyperbaric oxygen (HBO) The results verified Western blot ELISA. Then, short interfering RNA gene knockout further determine pivotal role of candidate HBO preconditioning–induced endogenous neuroprotection. Finally, lysosomal permeability tested elaborate mechanism underlying intrinsic neuroprotective effect. Results— Nine serum rats, which acquired benefits preconditioning, screened identified. ELISA revealed cystatin C (CysC) mannose-binding lectin protein uniquely changed with smaller infarction after ischemia. Knockdown CysC abolished HBO-induced Moreover, elevation preserved membrane integrity stroke wild-type but siRNA infusion or − /− rats. Most importantly, exogenous also against ischemic/reperfusion injury. Conclusions— a crucial determinant contributing It novel treatment through maintaining integrity.