Xiao-Fang Li1, Xiang-Jian Zhang2, Cong Zhang3, Li-Na Wang3, Yao-Ru Li4, Ye Zhang4, Ting-Ting He4, Xing-Yuan Zhu4, Li-Li Cui3, Bu-Lang Gao5. 1. Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. 2. Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-cerebrovascular Diseases, Shijiazhuang, Hebei, China. Electronic address: zhang6xj@aliyun.com. 3. Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-cerebrovascular Diseases, Shijiazhuang, Hebei, China. 4. Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-cerebrovascular Diseases, Shijiazhuang, Hebei, China. 5. Department of Interventional Treatment, Henan Provincial People's Hospital, Zhengzhou, Henan, China. Electronic address: browngao@163.com.
Abstract
BACKGROUND: The effects of Ulinastatin (UTI) on the blood-brain barrier (BBB) in the acute phase of cerebral ischemia/reperfusion (I/R) are not clear. This study was to investigate the potential protective effects of UTI on the BBB and the underlying mechanisms. METHODS: Male CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO) and randomly assigned to four groups: Sham (sham-operated), tMCAO (tMCAO+0.9% saline), UTI-L (tMCAO+UTI 1500U/100g) and UTI-H (tMCAO+UTI 3000U/100g) group. UTI was administered immediately after reperfusion in the UTI-L and UTI-H groups. At 24h after reperfusion, the neurological deficit, brain water content, and infarct volume were determined. Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to examine the expression of matrix metalloproteinase (MMP)-9, Zonula occludens-1 (ZO-1) and occludin in ischemic cerebral cortex. The integrity of the BBB was assessed by the leakage of Evans blue. RESULTS: Compared with tMCAO group, both UTI-L and UTI-H groups showed significantly (P<0.001) ameliorated the neurological deficit (2.00±0.71 and 1.60±0.55 vs. 4.60±0.55), lessened brain water content (82.99%±0.21% and 82.05%±0.59% vs. 84.28%±0.0.57%) and decreased the infarct volume (38.52%±1.72% and 24.78%±1.20% vs. 49.48%±1.93%). In addition, significantly (P<0.001) decreased expression of MMP-9 (0.48±0.06 and 0.37±0.05 vs.0.76±0.10 for protein and 2.88±0.23 and 2.17±0.16 vs. 3.90±0.24 for mRNA) and alleviated loss of ZO-1 (0.19±0.04 and 0.24±0.05 vs. 0.25±0.03) and occludin (0.74±0.08 and 0.87±0.07 vs. 0.94±0.06) proteins were observed in both UTI-L and UTI-H groups. CONCLUSION: UTI protects the brain against ischemic injury potentially via down-regulating the expression of MMP-9 and alleviating loss of ZO-1 and occludin proteins to restore the BBB permeability.
BACKGROUND: The effects of Ulinastatin (UTI) on the blood-brain barrier (BBB) in the acute phase of cerebral ischemia/reperfusion (I/R) are not clear. This study was to investigate the potential protective effects of UTI on the BBB and the underlying mechanisms. METHODS: Male CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO) and randomly assigned to four groups: Sham (sham-operated), tMCAO (tMCAO+0.9% saline), UTI-L (tMCAO+UTI 1500U/100g) and UTI-H (tMCAO+UTI 3000U/100g) group. UTI was administered immediately after reperfusion in the UTI-L and UTI-H groups. At 24h after reperfusion, the neurological deficit, brain water content, and infarct volume were determined. Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to examine the expression of matrix metalloproteinase (MMP)-9, Zonula occludens-1 (ZO-1) and occludin in ischemic cerebral cortex. The integrity of the BBB was assessed by the leakage of Evans blue. RESULTS: Compared with tMCAO group, both UTI-L and UTI-H groups showed significantly (P<0.001) ameliorated the neurological deficit (2.00±0.71 and 1.60±0.55 vs. 4.60±0.55), lessened brain water content (82.99%±0.21% and 82.05%±0.59% vs. 84.28%±0.0.57%) and decreased the infarct volume (38.52%±1.72% and 24.78%±1.20% vs. 49.48%±1.93%). In addition, significantly (P<0.001) decreased expression of MMP-9 (0.48±0.06 and 0.37±0.05 vs.0.76±0.10 for protein and 2.88±0.23 and 2.17±0.16 vs. 3.90±0.24 for mRNA) and alleviated loss of ZO-1 (0.19±0.04 and 0.24±0.05 vs. 0.25±0.03) and occludin (0.74±0.08 and 0.87±0.07 vs. 0.94±0.06) proteins were observed in both UTI-L and UTI-H groups. CONCLUSION: UTI protects the brain against ischemic injury potentially via down-regulating the expression of MMP-9 and alleviating loss of ZO-1 and occludin proteins to restore the BBB permeability.
Authors: Aric F Logsdon; Michelle A Erickson; Xiaodi Chen; Joseph Qiu; Yow-Pin Lim; Barbara S Stonestreet; William A Banks Journal: J Cereb Blood Flow Metab Date: 2019-06-24 Impact factor: 6.200
Authors: Ying Chen; Zhipeng Xu; Qi Song; Zhenjie Wang; Zhong Ji; Zhaolei Qiu; Feng Cheng; Hai Jiang Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2019-10-30
Authors: Xiaodi Chen; Sakura Nakada; John E Donahue; Ray H Chen; Richard Tucker; Joseph Qiu; Yow-Pin Lim; Edward G Stopa; Barbara S Stonestreet Journal: Exp Neurol Date: 2019-03-23 Impact factor: 5.330