Resveratrol Can Attenuate Astrocyte Activation to Treat Spinal Cord Injury by Inhibiting Inflammatory Responses

Fan, Ruihua; Zhang, Yong; Botchway, Benson O. A.; Liu, Xuehong

doi:10.1007/s12035-021-02509-4

Cited by 22 publications

(10 citation statements)

References 114 publications

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“…Resveratrol (Res), as a potential SCI therapeutic drug, exhibits a variety of pharmacological effects, such as good antioxidant, anti-inflammatory, neuroprotective, and antiapoptotic properties (Fu et al, 2018 ; Huang et al, 2019 ; Fan et al, 2021 ). However, due to its poor water solubility, low bioavailability, and difficulty in crossing physiological barriers to reach the injury site, its application in SCI is limited greatly (Zhang et al, 2014 ; Miguel et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Chitosan-modified hollow manganese dioxide nanoparticles loaded with resveratrol for the treatment of spinal cord injury

Zou

et al. 2022

Drug Delivery

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Spinal cord injury (SCI) is a serious central nervous system disease, and secondary injury, including oxidative stress, the inflammatory response and accompanying neuronal apoptosis, will aggravate the condition. Due to the existence of the blood–spinal cord barrier (BSCB), the existing drugs for SCI treatment are difficulty to reach the injury site and thus their efficacy is limited. In this study, we designed chitosan-modified hollow manganese dioxide nanoparticles (CM) for the delivery of resveratrol to help it pass through the BSCB. Resveratrol (Res), a poorly soluble drug, was adsorbed into CM with a particle size of approximately 130 nm via the adsorption method, and the drug loading reached 21.39 ± 2.53%. In vitro dissolution experiment, the Res release of the loaded sample (CMR) showed slowly release behavior and reached about 87% at 36 h. In vitro at the cellular level and in vivo at the animal level experiments demonstrated that CMR could alleviate significantly oxidative stress by reducing level of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and increasing glutathione peroxidase (GSH) level. Additionally, immunofluorescence (iNOS, IL-1β, and Cl caspase-3) and western blot (iNOS, cox-2, IL-1β, IL-10, Cl caspase-3, bax, and bcl-2) were used to detect the expression of related factors, which verified that CMR could also reduce inflammation and neuronal apoptosis. These results indicated that CM, as a potential central nervous system drug delivery material, was suitable for SCI treatment.

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Section: Introductionmentioning

confidence: 99%

Chitosan-modified hollow manganese dioxide nanoparticles loaded with resveratrol for the treatment of spinal cord injury

Zou

et al. 2022

Drug Delivery

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“…The reason that injured CNS would ever produce a neurotoxic reactive astrocyte is still a mystery. Drugs that prevent or revert these subtype of reactive astrocytes may save neurons after spinal cord injury and promote regeneration by stimulating growth and allowing these astrocytes to clear myelin debris (Fan et al, 2021). Oligodendrocytes also display high cell stress levels (Hapln2, Hspa8, and Hsp90ab1), with GO analysis showing many differentially regulated metabolic processes after injury, which indicates that oligodendrocytes transit from a normal to active state.…”

Section: Discussionmentioning

confidence: 99%

Molecular Expression Profile of Changes in Rat Acute Spinal Cord Injury

Wang¹,

Ye²,

Ren³

et al. 2021

Front. Cell. Neurosci.

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Background: Spinal cord injury (SCI) is a highly lethal and debilitating disease with a variety of etiologies. To date, there is no effective therapeutic modality for a complete cure. The pathological mechanisms of spinal cord injury at the molecular gene and protein expression levels remain unclear.Methods: This study used single-cell transcriptomic analysis and protein microarray analysis to analyzes changes in the gene expression profiles of cells and secretion of inflammatory factors respectively, around the lesion site in a rat SCI model.Results: Single-cell transcriptomic analysis found that three types of glial cells (microglia, astrocyte, and oligodendrocyte) becomes activated after acute injury, with GO exhibiting a variety of inflammatory-related terms after injury, such as metabolic processes, immune regulation, and antigen presentation. Protein microarray results showed that the levels of four inflammatory cytokines favoring SCI repair decreased while the levels of nine inflammatory cytokines hindering SCI repair increased after injury.Conclusion: These findings thus reveal the changes in cellular state from homeostatic to reactive cell type after SCI, which contribute to understand the pathology process of SCI, and the potential relationship between glial cells and inflammatory factors after SCI, and provides new theoretical foundation for further elucidating the molecular mechanisms of secondary SCI.

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“…With substantial advances in the understanding of SCI pathophysiology, it was gradually revealed that the early inflammatory response could also generate a permissive microenvironment for the regeneration of damaged neurons and axons, similar to early inflammatory benefits in other tissues. [57][58][59] Neuroinflammation is composed of multifaceted cellular and molecular responses, and the unique effects of immune cells including macrophages, astrocytes, and lymphocytes are essential for the occurrence and progression of inflammatory responses post-SCI. 60…”

Section: Contribution Of Distinct Immune Cells To Sci Inflammationmentioning

confidence: 99%

Regulatory Role of Mesenchymal Stem Cells on Secondary Inflammation in Spinal Cord Injury

QM¹,

Sy²,

SP³

et al. 2022

JIR

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Spinal cord injury (SCI) is a catastrophic condition with high morbidity and mortality that still lacks effective therapeutic strategies. It is well known that the most important stage in SCI pathogenesis is secondary injury, and among the involved mechanisms, the inflammatory cascade is the main contributor and directly influences neurological function recovery. In recent years, increasing evidence has shown that mesenchymal stem cells (MSCs) transplantation is a promising immunomodulatory strategy. Transplanted MSCs can regulate macrophage-, astrocyte-, and T lymphocyte-mediated neuroinflammation and help create a microenvironment that facilitates tissue repair and regeneration. This review focuses on the effects of different types of immune cells and MSCs, specifically the immunoregulatory capacity of MSCs in SCI and repair. We will also discuss how to exploit MSCs transplantation to regulate immune cells and develop novel therapeutic strategies for SCI.

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Resveratrol Can Attenuate Astrocyte Activation to Treat Spinal Cord Injury by Inhibiting Inflammatory Responses

Cited by 22 publications

References 114 publications

Chitosan-modified hollow manganese dioxide nanoparticles loaded with resveratrol for the treatment of spinal cord injury

Chitosan-modified hollow manganese dioxide nanoparticles loaded with resveratrol for the treatment of spinal cord injury

Molecular Expression Profile of Changes in Rat Acute Spinal Cord Injury

Regulatory Role of Mesenchymal Stem Cells on Secondary Inflammation in Spinal Cord Injury

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