期刊
GEROSCIENCE
卷 41, 期 5, 页码 543-559出版社
SPRINGER
DOI: 10.1007/s11357-019-00118-7
关键词
Amyloid-beta; Astrocyte; Basement membrane; Cerebrospinal fluid; Stroke; TGF-beta
资金
- NIH/NIA [RF1AG057576]
- NIH/NINDS [R01NS094543]
- American Heart Association [AHA17PRE33410369]
- NIH [4TL1TR000369-10]
- state of Texas, through the Texas Council on Alzheimer's Disease and Related Disorders
Aging and stroke alter the composition of the basement membrane and reduce the perivascular distribution of cerebrospinal fluid and solutes, which may contribute to poor functional recovery in elderly patients. Following stroke, TGF-beta induces astrocyte activation and subsequent glial scar development. This is dysregulated with aging and could lead to chronic, detrimental changes within the basement membrane. We hypothesized that TGF-beta induces basement membrane fibrosis after stroke, leading to impaired perivascular CSF distribution and poor functional recovery in aged animals. We found that CSF entered the aged brain along perivascular tracts; this process was reduced by experimental stroke and was rescued by TGF-beta receptor inhibition. Brain fibronectin levels increased with experimental stroke, which was reversed with inhibitor treatment. Exogenous TGF-beta stimulation increased fibronectin expression, both in vivo and in primary cultured astrocytes. Oxygen-glucose deprivation of cultured astrocytes induced multiple changes in genes related to astrocyte activation and extracellular matrix production. Finally, in stroke patients, we found that serum TGF-beta levels correlated with poorer functional outcomes, suggesting that serum levels may act as a biomarker for functional recovery. These results support a potential new treatment strategy to enhance recovery in elderly stroke patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据