Resveratrol suppresses microglial activation and promotes functional recovery of traumatic spinal cord via improving intestinal microbiota

He, Na; Shen, Guo‐Ping; Jin, Xiaoqin; Li, Heyangzi; Wang, Jingyu; Xu, Lingxiao; Cao, Xi; Fu, Chunyan; Shi, Dongling; Song, Xinghui; Liu, Shuangshuang; Li, Yanwei; Zhao, Tengfei; Li, Jun; Zhong, Jinjie; Shen, Yueliang; Zheng, Mingfeng; Chen, Yingying; Wang, Linlin

doi:10.1016/j.phrs.2022.106377

Cited by 31 publications

(13 citation statements)

References 66 publications

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“…The recovery of motor function from SCI is a relatively long process; hence, we performed footprint testing 35 days post injury as well as perform BMS scoring at different stages throughout the process. Through BMS scoring and footprint testing, we found that resveratrol can promote the recovery of motor function post-SCI, which is consistent with previous reports (He et al, 2022;Hu et al, 2017). The results of this experiment show that resveratrol can improve the motor function of mice post-SCI.…”

Section: Discussionsupporting

confidence: 92%

Resveratrol inhibits ferroptosis via activating NRF2/GPX4 pathway in mice with spinal cord injury

et al. 2023

Microscopy Res & Technique

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Ferroptosis is a newly defined form of cell death involved in neurologic disease. Resveratrol is a non‐flavonoid polyphenolic compound with anti‐inflammatory and antioxidant properties, but its potential therapeutic mechanism in spinal cord injury (SCI) remains unknown. Therefore, this study evaluates the mechanism by which resveratrol promotes neurological and motor function recovery in mice with SCI. The motor function of mice was evaluated using the Basso Mouse Scale score and footprint test. The effect of resveratrol on the neuronal cell state was observed using NeuN, fluoro‐Jade C, and Nissl staining. The expression of iron content in injured segments was observed using Perls blue and Diaminobenzidine staining. The effect of resveratrol on the levels of malondialdehyde, glutathione, Fe2+, and glutathione peroxidase 4 enzyme activity was also investigated. The mitochondrial ultrastructures of injured segment cells were observed using transmission electron microscope, while the protein levels of ferroptosis‐related targets were detected using Western blot. Our findings show that resveratrol improves motor function after SCI and has certain neuroprotective effects; in ferroptosis‐related studies, resveratrol inhibited the expression of ferroptosis‐related proteins and ions. Resveratrol improved changes in mitochondrial morphology. Mechanistically, the Nrf2 inhibitor ML385 reversed the inhibitory effect of resveratrol on ferroptosis‐related genes, indicating that resveratrol inhibits ferroptosis through the Nrf2/GPX4 pathway. Our findings elucidate that resveratrol promotes functional recovery, inhibits ferroptosis post‐SCI, and provides an experimental basis for subsequent clinical translational research.

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Section: Discussionsupporting

confidence: 92%

Resveratrol inhibits ferroptosis via activating NRF2/GPX4 pathway in mice with spinal cord injury

et al. 2023

Microscopy Res & Technique

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“…In support of these findings, a previous study found that RSV treatment increased the abundance of Lactobacillus in the fecal microbiota. 34 Notably, an increase in Helicobacter may trigger the F I G U R E 6 Pearson's correlations between microbial taxa, neurotransmitters and behaviors. The scale (right legend) represents the degree of positive (red) or negative (blue) correlation.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol alleviates perinatal methylmercury‐induced neurobehavioral impairments by modulating the gut microbiota composition and neurotransmitter disturbances

Chen,

Zhang,

Liu

et al. 2023

Environmental Toxicology

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Methylmercury (MeHg), a potent neurotoxic substance, causes adverse health outcomes by modulating metabolites through altered gut microbiota patterns. Among the many metabolites, neurotransmitters play a particularly important role in the nervous system and behavior. Resveratrol (RSV) has been investigated as an antiaging, antioxidant, anti‐inflammatory, and neuroprotective agent. The current study evaluated that RSV is protective of neurodevelopmental toxicity induced by MeHg and further explored the underlying mechanisms. Sprague–Dawley rats were treated with 1.2 mg/kg/d of MeHg, and the effects were evaluated after supplementation with RSV (20 mg/kg/d). The results indicated that MeHg had adverse effects on early neurodevelopmental indicators in the experimental group offspring as compared to control pups. Interestingly, RSV significantly improved the MeHg‐induced delays in the neurobehavioral reflexes and reduced the total mercury (THg) concentration in the colons of the offspring rats. In agreement, RSV administration improved the gut microbiota diversity and structure by increasing the abundance of probiotics and upregulating the expression of tight junction proteins. It also ameliorated the MeHg‐induced abnormalities in the expression profiles of neurotransmitters. Furthermore, eight key bacteria that were strongly linked with the neurotransmitters and neuroreflex parameters were identified. Taken together, these results demonstrate that RSV treatment effectively reduces the occurrence of neurodevelopmental toxicity caused by perinatal MeHg exposure by modulating the intestinal flora and neurotransmitter metabolism. These findings provide a new therapeutic approach for treating MeHg‐induced neurotoxicity.

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“…The recovery of locomotor function after SCI is usually evaluated using Basso Mouse Scale (BMS) scoring and footprint analysis. [40] BMS score and subscore provide reliable assessment for hindlimb movement, while stride length in footprint test reveals forelimb-hindlimb coordination. After SCI, the mice displayed a slow spontaneous recovery of motor function characterized by reduced BMS score and subscore, and an decreased stride length hindlimb dragging (p < 0.01 vs sham, Figure 6e-i).…”

Section: Intracerebroventricular Injection Of Mms6-transfected M2 Mac...mentioning

confidence: 99%

“…Immunofluorescence Staining: MAP2 immunofluorescence staining was performed to detect the neuronal cells in the injured spinal cord according to a previously published protocol. [40] Briefly, paraffin sections of spinal cords were de-paraffinized and rehydrated. Then sections were incubated overnight in a blocking solution containing primary antibodies against MAP2 (rabbit, 8707, Cell Signaling Technology, 1:100) and GFAP (chicken, ab4674, Abcam, 1:200), overnight at 4 °C.…”

Section: Measurement Of M2 Macrophages In Spinal Cords Using Fluoresc...mentioning

confidence: 99%

Magnetotactic Bacteria‐Derived Mms6 Gene Helps M2 Macrophages to Form Magnetic Bio‐Nanoparticles to Prevent Ferroptosis and Promote Locomotor Functional Recovery after Spinal Cord Injury in Mice

Fu,

Mao,

Jin

et al. 2023

Adv Funct Materials

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Magnetotactic bacteria are microaerobic microorganisms that take up iron from solution and crystallize magnetite nanoparticles called magnetosomes, enclosed by membrane intracellularly and mainly formed by the magnetosome membrane‐specific 6 (Mms6) gene. M2 macrophages are transfected by magnetotactic bacteria‐derived Mms6 gene to form magnetic bio‐nanoparticles. Under myelin debris‐rich hypoxic stress in the spinal cord injury (SCI) microenvironment, Mms6‐transfected M2 macrophages can antagonize ferroptosis. Meanwhile, transplantation of Mms6‐transfected M2 macrophages into SCI mice through intracerebroventricular or intravenous injection can effectively promote structural repair and locomotor functional recovery. As a proof of concept, this study provides a novel strategy in immune cell therapy, which supports the survival and strengthens the function of M2 macrophages based on magnetic bio‐nanoparticles which help M2 macrophages to resist ferroptosis. This study also sheds light on this cross‐species applications for treating traumatic injury and inflammatory diseases.

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Resveratrol suppresses microglial activation and promotes functional recovery of traumatic spinal cord via improving intestinal microbiota

Cited by 31 publications

References 66 publications

Resveratrol inhibits ferroptosis via activating NRF2/GPX4 pathway in mice with spinal cord injury

Resveratrol inhibits ferroptosis via activating NRF2/GPX4 pathway in mice with spinal cord injury

Resveratrol alleviates perinatal methylmercury‐induced neurobehavioral impairments by modulating the gut microbiota composition and neurotransmitter disturbances

Magnetotactic Bacteria‐Derived Mms6 Gene Helps M2 Macrophages to Form Magnetic Bio‐Nanoparticles to Prevent Ferroptosis and Promote Locomotor Functional Recovery after Spinal Cord Injury in Mice

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