Sodium tanshinone IIA sulfonate promotes spinal cord injury repair by inhibiting blood spinal cord barrier disruption in vitro and in vivo

Abstract Background:Spinal cord injury (SCI) leads to microvascular damage and the destruction of blood spinal cord barrier (BSCB), which progresses to secondary injuries like apoptosis and necrosis of neurons and glia, culminating in permanent neurological deficits. BSCB restoration is the primary goal of SCI therapy, although very few drugs can repair the damaged barrier structure and permeability. Sodium tanshinone IIA sulfonate (STS) is commonly used to treat cardiovascular disease. We found that STS restored BSCB integrity and promoted microvessel recovery 7 days after SCI in a mouse model. However, the therapeutic effects of STS on damaged BSCB in the early stage of SCI remained uncertain. Methods: we exposed spinal cord microvascular endothelial cells (SCMECs) to H2O2 and treated them with different doses of STS. The mice received intraperitoneal injection of STS after SCI in vivo model. Spinal cord tissue was taken 1 and 3d post-SCI. HE, Nissl staining, BSCB permeability, and the expression levels of tight junction (TJ) and adherens junction (AJ), MMP2, MMP9, NeuN, and C-caspase-3 were analyzed.Results: In addition to protecting the cells from H2O2-induced apoptosis, STS also reduced cellular permeability. In the in vivo model of SCI as well, STS reduced BSCB permeability, relieved tissue edema and hemorrhage, suppressed MMPs activation and prevented TJ and AJ the loss of proteins. Conclusions:Our findings indicate that STS treatment promotes SCI recovery, and should be investigated further as a drug candidate against traumatic SCI.

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Retraction notice to “Tanshinone IIA alleviates oxidative damage after spinal cord injury in vitro and in vivo through up-regulating miR-124” [Life Sci. 216 (2019) 147–155]

Life Sciences ◽

10.1016/j.lfs.2020.117497 ◽

2020 ◽

Vol 249 ◽

pp. 117497

Author(s):

Gu Gong ◽

Yiqi Gu ◽

Yunfeng Zhang ◽

Wanguo Liu ◽

Li Li ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Oxidative Damage ◽

Tanshinone Iia ◽

Cord Injury ◽

Retraction Notice

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RETRACTED: Tanshinone IIA alleviates oxidative damage after spinal cord injury in vitro and in vivo through up-regulating miR-124

Life Sciences ◽

10.1016/j.lfs.2018.11.046 ◽

2019 ◽

Vol 216 ◽

pp. 147-155 ◽

Cited By ~ 4

Author(s):

Gu Gong ◽

Yiqi Gu ◽

Yunfeng Zhang ◽

Wanguo Liu ◽

Li Li ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Oxidative Damage ◽

Tanshinone Iia ◽

Cord Injury

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A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

Polymers ◽

10.3390/polym12102245 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2245

Author(s):

Jue-Zong Yeh ◽

Ding-Han Wang ◽

Juin-Hong Cherng ◽

Yi-Wen Wang ◽

Gang-Yi Fan ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Rat Model ◽

Neural Plasticity ◽

Collagen Scaffold ◽

Glial Scar ◽

Beneficial Effects ◽

Cord Injury

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

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Immunosuppressants Affect Human Neural Stem Cells In Vitro but Not in an In Vivo Model of Spinal Cord Injury

Stem Cells Translational Medicine ◽

10.5966/sctm.2012-0175 ◽

2013 ◽

Vol 2 (10) ◽

pp. 731-744 ◽

Cited By ~ 21

Author(s):

Christopher J. Sontag ◽

Hal X. Nguyen ◽

Noriko Kamei ◽

Nobuko Uchida ◽

Aileen J. Anderson ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Neural Stem Cells ◽

In Vivo Model ◽

Human Neural Stem Cells ◽

Cord Injury

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Depolarization and electrical stimulation enhance in vitro and in vivo sensory axon growth after spinal cord injury

Experimental Neurology ◽

10.1016/j.expneurol.2017.11.011 ◽

2018 ◽

Vol 300 ◽

pp. 247-258 ◽

Cited By ~ 12

Author(s):

Ioana Goganau ◽

Beatrice Sandner ◽

Norbert Weidner ◽

Karim Fouad ◽

Armin Blesch

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Electrical Stimulation ◽

Axon Growth ◽

Sensory Axon ◽

Cord Injury

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Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury

Mediators of Inflammation ◽

10.1155/2016/9476020 ◽

2016 ◽

Vol 2016 ◽

pp. 1-21 ◽

Cited By ~ 34

Author(s):

Elisa Garcia ◽

Jorge Aguilar-Cevallos ◽

Raul Silva-Garcia ◽

Antonio Ibarra

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Critical Role ◽

Glutamate Excitotoxicity ◽

Signaling Proteins ◽

Neurodegenerative Process ◽

Cord Injury ◽

Ion Imbalance

Spinal cord injury results in a life-disrupting series of deleterious interconnected mechanisms encompassed by the primary and secondary injury. These events are mediated by the upregulation of genes with roles in inflammation, transcription, and signaling proteins. In particular, cytokines and growth factors are signaling proteins that have important roles in the pathophysiology of SCI. The balance between the proinflammatory and anti-inflammatory effects of these molecules plays a critical role in the progression and outcome of the lesion. The excessive inflammatory Th1 and Th17 phenotypes observed after SCI tilt the scale towards a proinflammatory environment, which exacerbates the deleterious mechanisms present after the injury. These mechanisms include the disruption of the spinal cord blood barrier, edema and ion imbalance, in particular intracellular calcium and sodium concentrations, glutamate excitotoxicity, free radicals, and the inflammatory response contributing to the neurodegenerative process which is characterized by demyelination and apoptosis of neuronal tissue.

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Docosahexaenoic Acid-Loaded Polylactic Acid Core-Shell Nanofiber Membranes for Regenerative Medicine after Spinal Cord Injury: In Vitro and In Vivo Study

International Journal of Molecular Sciences ◽

10.3390/ijms21197031 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7031

Author(s):

Zhuo-Hao Liu ◽

Yin-Cheng Huang ◽

Chang-Yi Kuo ◽

Chao-Ying Kuo ◽

Chieh-Yu Chin ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Docosahexaenoic Acid ◽

Neurite Outgrowth ◽

Polylactic Acid ◽

In Vivo Study ◽

Core Shell ◽

Cord Injury

Spinal cord injury (SCI) is associated with disability and a drastic decrease in quality of life for affected individuals. Previous studies support the idea that docosahexaenoic acid (DHA)-based pharmacological approach is a promising therapeutic strategy for the management of acute SCI. We postulated that a nanostructured material for controlled delivery of DHA at the lesion site may be well suited for this purpose. Toward this end, we prepare drug-loaded fibrous mats made of core-shell nanofibers by electrospinning, which contained a polylactic acid (PLA) shell for encapsulation of DHA within the core, for delivery of DHA in situ. In vitro study confirmed sustained DHA release from PLA/DHA core-shell nanofiber membrane (CSNM) for up to 36 days, which could significantly increase neurite outgrowth from primary cortical neurons in 3 days. This is supported by the upregulation of brain-derived neurotropic factor (BDNF) and neurotrophin-3 (NT-3) neural marker genes from qRT-PCR analysis. Most importantly, the sustained release of DHA could significantly increase the neurite outgrowth length from cortical neuron cells in 7 days when co-cultured with PLA/DHA CSNM, compared with cells cultured with 3 μM DHA. From in vivo study with a SCI model created in rats, implantation of PLA/DHA CSNM could significantly improve neurological functions revealed by behavior assessment in comparison with the control (no treatment) and the PLA CSNM groups. According to histological analysis, PLA/DHA CSNM also effectively reduced neuron loss and increased serotonergic nerve sprouting. Taken together, the PLA/DHA CSNM may provide a nanostructured drug delivery system for DHA and contribute to neuroprotection and promoting neuroplasticity change following SCI.

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