A2B5-positive oligodendrocyte precursor cell transplantation improves neurological deficits in rats following spinal cord contusion associated with changes in expression of factors involved in Notch signaling pathway

Abstract Background The therapeutic effects of adipose-derived mesenchymal stem cell (ADSC) transplantation have been demonstrated in several models of central nervous system (CNS) injury and are thought to involve the modulation of the inflammatory response. However, the exact underlying molecular mechanism is poorly understood. Activation of the Jagged1/Notch signaling pathway is thought to involve inflammatory and gliotic events in the CNS. Here, we elucidated the effect of ADSC transplantation on the inflammatory reaction after spinal cord injury (SCI) and the potential mechanism mediated by Jagged1/Notch signaling pathway suppression.Methods Using a mouse model of compression SCI, ADSCs and Jagged1 small interfering RNA (siRNA) were injected into the spinal cord. Locomotor function, spinal cord tissue morphology and the levels of various proteins and transcripts were compared between groups.Results ADSC treatment resulted in significant downregulation of proinflammatory mediator expression and reduced ionized calcium binding adapter molecule 1 (Iba1) and ED1 staining in the injured spinal cord, promoting the survival of neurons. These changes were accompanied by improved functional recovery. The augmentation of the Jagged1/Notch signaling pathway after SCI was suppressed by ADSC transplantation. The inhibition of the Jagged1/Notch signaling pathway by Jagged1 siRNA resulted in a decrease in SCI-induced proinflammatory cytokines as well as the activation of microglia. Furthermore, Jagged1 knockdown suppressed the phosphorylation of JAK/STAT3 following SCI.Conclusion The results of this study demonstrated that the therapeutic effects of ADSCs in SCI mice were partly due to Jagged1/notch signaling pathway inhibition and a subsequent reduction in JAK/STAT3 phosphorylation.

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Activation of the Notch Signaling Pathway and Cellular Localization of Notch Signaling Molecules in the Spinal Cord of SOD1-G93A ALS Model Mice

Neuroscience ◽

10.1016/j.neuroscience.2020.02.034 ◽

2020 ◽

Vol 432 ◽

pp. 84-93 ◽

Cited By ~ 1

Author(s):

Chong Liu ◽

Dongxiao Li ◽

Cui Lv ◽

Zhisong Gao ◽

Yinkuang Qi ◽

...

Keyword(s):

Spinal Cord ◽

Notch Signaling ◽

Signaling Pathway ◽

Cellular Localization ◽

Notch Signaling Pathway ◽

Signaling Molecules

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Sodium Tanshinone IIA Silate Exerts Microcirculation Protective Effects against Spinal Cord Injury In Vitro and In Vivo

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/3949575 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Xing Li ◽

Dan Luo ◽

Yu Hou ◽

Yonghui Hou ◽

Shudong Chen ◽

...

Keyword(s):

Spinal Cord ◽

Endothelial Cells ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Tanshinone Iia ◽

Protective Effects ◽

Cord Injury

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.

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Resveratrol can inhibit Notch signaling pathway to improve spinal cord injury

Annals of Anatomy - Anatomischer Anzeiger ◽

10.1016/j.aanat.2019.01.015 ◽

2019 ◽

Vol 223 ◽

pp. 100-107 ◽

Cited By ~ 2

Author(s):

Songou Zhang ◽

Benson O.A. Botchway ◽

Yong Zhang ◽

Xuehong Liu

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Cord Injury

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Oligodendrocyte precursor cell transplantation promotes angiogenesis and remyelination via Wnt/β-catenin pathway in a mouse model of middle cerebral artery occlusion

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211065391 ◽

2021 ◽

pp. 0271678X2110653

Author(s):

Li-Ping Wang ◽

Jiaji Pan ◽

Yongfang Li ◽

Jieli Geng ◽

Chang Liu ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Cell Transplantation ◽

Artery Occlusion ◽

Precursor Cells ◽

Precursor Cell ◽

Oligodendrocyte Precursor Cells ◽

Oligodendrocyte Precursor Cell ◽

Oligodendrocyte Precursor ◽

Cerebral Artery Occlusion

White matter injury is a critical pathological characteristic during ischemic stroke. Oligodendrocyte precursor cells participate in white matter repairing and remodeling during ischemic brain injury. Since oligodendrocyte precursor cells could promote Wnt-dependent angiogenesis and migrate along vasculature for the myelination during the development in the central nervous system, we explore whether exogenous oligodendrocyte precursor cell transplantation promotes angiogenesis and remyelination after middle cerebral artery occlusion in mice. Here, oligodendrocyte precursor cell transplantation improved motor and cognitive function, and alleviated brain atrophy. Furthermore, oligodendrocyte precursor cell transplantation promoted functional angiogenesis, and increased myelin basic protein expression after ischemic stroke. The further study suggested that white matter repairing after oligodendrocyte precursor cell transplantation depended on angiogenesis induced by Wnt/β-catenin signal pathway. Our results demonstrated a novel pathway that Wnt7a from oligodendrocyte precursor cells acting on endothelial β-catenin promoted angiogenesis and improved neurobehavioral outcomes, which facilitated white matter repair and remodeling during ischemic stroke.

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