Astragoloside IV Loaded Polycaprolactone Membrane Repairs Blood Spinal Cord Barrier and Recovers Spinal Cord Function in Traumatic Spinal Cord Injury.
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY(2019)
摘要
Traumatic Spinal Cord Injury (SCI) is a serious challenge of CNS which may oftenly result in permanent paralysis and disability. The disruption of blood spinal cord barrier (BSCB) is a major step in the secondary injury of SCI. Until recently there are no restorative therapies for traumatic SCI. BSCB is considered to be a therapeutic target for SCI, however few biomaterials have been developed to restore the disrupted BSCB in SCI. In this study, an AST-PCL membrane was fabricated with a steady release of Astragoloside IV (AST) and its effects on BSCB repair as well as the functional recovery of SCI were evaluated. Firstly, this study demonstrated that AST-PCL (polycaprolactone) degradation media protects endothelial cells from apoptosis by down-regulating the expression of cleaved Caspase 3 and decreasing the ratio of Bax/Bcl-2, it also attenuates the stress fiber formation in vitro. Secondly, the rat model of traumatic SCI showed that AST-PCL treatment inhibits the disruption of BSCB permeability, as detected by MRI, Evan's Blue extravasation and water content. Thirdly, this study found that AST-PCL up-regulates the level of tight junction proteins including Occludin, Claudin-5 and ZO-1. Furthermore, it is also demonstrated that AST-PCL treatment down-regulates Matrix metalloproteinase-9 secretion and diminishes neutrophil infiltration. Finally, this study found that AST-PCL treatment could significantly inhibit apoptosis, decrease tissue damage and improve functional recovery in SCI rats. Taken together, this study shows that AST-PCL might be an efficient biomaterial for BSCB repair and a potential drug therapy for SCI.
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关键词
Spinal Cord Injury,Blood Spinal Cord Barrier,Local Drug Delivery,Astragoloside IV,Matrix Metalloproteinase-9,Neutrophil
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