Abstract
Spinal cord microcirculation involves functioning endothelial cells at the blood spinal cord barrier (BSCB) and maintains normal functioning of spinal cord neurons, axons, and glial cells. Protection of both the function and integrity of endothelial cells as well as the prevention of BSCB disruption may be a strong strategy for the treatment of spinal cord injury (SCI) cases. Sodium Tanshinone IIA silate (STS) is used for the treatment of coronary heart disease and improves microcirculation. Whether STS exhibits protective effects for SCI microcirculation is not yet clear. The purpose of this study is to investigate the protective effects of STS on oxygen-glucose deprivation- (OGD-) induced injury of spinal cord endothelial cells (SCMECs) in vitro and to explore effects on BSCB and neurovascular protection in vivo. SCMECs were treated with various concentrations of STS (1 μM, 3 μM, and 10 μM) for 24 h with or without OGD-induction. Cell viability, tube formation, migration, and expression of Notch signaling pathway components were evaluated. Histopathological evaluation (H&E), Nissl staining, BSCB permeability, and the expression levels of von Willebrand Factor (vWF), CD31, NeuN, and Notch signaling pathway components were analyzed. STS was found to improve SCMEC functions and reduce inflammatory mediators after OGD. STS also relieved histopathological damage, increased zonula occludens-1 (ZO-1), inhibited BSCB permeability, rescued microvessels, protected motor neuromas, and improved functional recovery in a SCI model. Moreover, we uncovered that the Notch signaling pathway plays an important role during these processes. These results indicated that STS protects microcirculation in SCI, which may be used as a therapeutic strategy for SCI in the future.
Highlights
Spinal cord injury (SCI) is a major medical issue that can lead to permanent paraplegia [1]
The pericyte marker NG-2 and the astrocyte maker GFAP were not expressed (Figure 2(b)). These results indicated that there were no pericytes or astrocytes mixed in SCMEC cultures
There is a greater number of patients with SCI in China compared to other countries [42]
Summary
Spinal cord injury (SCI) is a major medical issue that can lead to permanent paraplegia [1]. At the primary mechanical injury stage, compression damages pericytes and endothelial cells, fractures blood vessels, and disturbs the blood spinal cord barrier (BSCB), which results in vascular imbalances and leads to severe secondary injury and functional disability [11, 12]. After SCI, BSCB breaks down and neurotoxic products and immune cells infiltrate into the injured parenchyma, which contributes to secondary damage [13,14,15]. These secondary injuries result in the death of neurons and glia and permanent neurological disability [15, 16]. Protecting the function and integrity of endothelial cells and preventing BSCB disruption are necessary to decrease severe secondary injury, which may serve as a potential therapeutic strategy for SCI
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