Excess salt exacerbates blood-brain barrier disruption via a p38/MAPK/SGK1-dependent pathway in permanent cerebral ischemia

被引:53
作者
Zhang, Tongshuai [1 ]
Fang, Shaohong [2 ]
Wan, Cong [1 ]
Kong, Qingfei [1 ]
Wang, Guangyou [1 ]
Wang, Shuangshuang [1 ]
Zhang, Haoqiang [1 ]
Zou, Haifeng [1 ]
Sun, Bo [1 ]
Sun, Wei [3 ]
Zhang, Yao [1 ]
Mu, Lili [1 ]
Wang, Jinghua [1 ]
Wang, Jing [3 ]
Zhang, Haiyu [4 ]
Wang, Dandan [1 ]
Li, Hulun [1 ]
机构
[1] Harbin Med Univ, Dept Neurobiol, Harbin 150081, Peoples R China
[2] Harbin Med Univ, Affiliated Hosp 2, Key Lab Myocardial Ischemia, Harbin 150081, Peoples R China
[3] Harbin Med Univ, Affiliated Hosp 1, Dept Neurol, Harbin 150081, Peoples R China
[4] Harbin Med Univ, Dept Epidemiol & Biostat, Harbin 150081, Peoples R China
基金
中国国家自然科学基金; 黑龙江省自然科学基金;
关键词
TIGHT JUNCTIONS; KINASE; PERMEABILITY; CELLS; SERUM; STROKE; RECRUITMENT; NEUTROPHILS; EXPRESSION; INDUCTION;
D O I
10.1038/srep16548
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
High salt diet (HSD) is one of the most important risk factors that contribute to many vascular diseases including ischemic stroke. One proposed mechanism underlying the disruption of blood-brain barrier (BBB) mediated by HSD is indirectly through enhancing blood pressure. The direct role of HSD on BBB integrity is unclear. Our purpose is to determine whether and how HSD might be involved in BBB breakdown during ischemia. To test that, we induced model of cerebral ischemia by permanent middle cerebral artery ligation (pMCAL) in either normal diet or HSD fed mice. We observed that HSD significantly enhanced ischemic brain damage which was associated with enhanced BBB disruption, increased leukocytes infiltration and loss of tight junction (TJ) proteins expression without apparently altering blood pressure. Our in vitro experiment also revealed that sodium chloride (NaCl) treatment down-regulated TJ protein expression by endothelial cells and substantially increased BBB permeability during starvation. Inhibition of p38/MAPK/SGK1 pathway eliminated the effect of NaCl on BBB permeability in vitro. In addition, we noticed a positive correlation between urinary sodium levels and ischemic lesion size in stroke patients. Together, our study demonstrates a hypertension-independent role of HSD during ischemia and provides rationale for post cerebral ischemic attack management.
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页数:12
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