Journal
GEROSCIENCE
Volume 41, Issue 5, Pages 543-559Publisher
SPRINGER
DOI: 10.1007/s11357-019-00118-7
Keywords
Amyloid-beta; Astrocyte; Basement membrane; Cerebrospinal fluid; Stroke; TGF-beta
Categories
Funding
- 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
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available