Cystatin C Improves Blood ‐Brain Barrier Integrity After Ischemic Brain Injury in Mice

AbstractCystatin C, a well ‐established biomarker of renal function, has been associated with a protective effect against stroke. However, the potential neuroprotective mechanism of cystatin C in ischemic brain injury remains unclear. Our study hypothesized that cystatin C can ameliorate blood‐brain barrier (BBB) disrupti on by upregulating caveolin‐1 expression, thereby improving neurological outcomes in cerebral ischemic injury. Western blotting, immunohistochemistry, immunofluorescence staining, and immunoprecipitation were performed to investigate target proteins. Evans Blue and gelatin zymography were used to examine the effect of cystatin C on BBB disruption. Plasmid and small interfering RNA (siRNA) transfection was used to observe alterations in caveolin‐1 and occludin expression induced by changes in cystatin C expression. Intriguingly, our study showed that the expression of both cystatin C and ca veolin‐1 was increased in middle cerebral artery occlusion (MCAO)‐injured mice, and pretreatment with exogenous cystatin C significantly increased caveolin‐1 expression, reduced Evans Blue leakage in the injured brain region, and decreased the enzymatic activity of matrix metallopeptidase‐9 (MMP‐9). Meanwhile, our study also showed that the overexpression of cystatin C greatly enhanced caveolin‐1 expression, which later increased occludin expression in oxygen‐glucose deprivation (OGD)‐exposed brain microvascular endothelial (bEnd.3) cells. On the o...

Source: Journal of Neurochemistry - October 10, 2019 Category: Neuroscience Authors: Bo Yang, Junjie Xu, Liuhui Chang, Zhigang Miao, Dara Heang, Yuwei Pu, Xun Zhou, Lingwei Zhang, Hong Xie Tags: ORIGINAL ARTICLE Source Type: research