Transforming Growth Factor β1 Ameliorates Microglial Activation in Perioperative Neurocognitive Disorders

Lin, Dandan; Sun, Yi; Wang, Yuzhu; Yang, Di; Shui, Min; Wang, Yiming; Xue, Ziyi; Huang, Xiao; Zhang, Yan; Wu, Anshi; Wei, Changwei

doi:10.1007/s11064-023-03994-w

Neurochem Res

2023

DOI: 10.1007/s11064-023-03994-w

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Transforming Growth Factor β1 Ameliorates Microglial Activation in Perioperative Neurocognitive Disorders

Dandan Lin

Yi Sun

Yuzhu Wang

et al.

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2024

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Cited by 2 publications

References 53 publications

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Sinomenine Ameliorated Microglial Activation and Neuropathic Pain After Chronic Constriction Injury Via TGF‐β1/ALK5/Smad3 Signalling Pathway

Ling,

Luo,

Yin

et al. 2024

J Cellular Molecular Medi

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Sinomenine (SIN), a bioactive isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, is efficacious against various chronic pain conditions. Inhibition of microglial activation at the spinal level contributes to the analgesic effects of SIN. Microglial activation in the spinal dorsal horn is key to sensitising neuropathic pain. Consequently, this study aimed to investigate whether the antinociceptive effects of SIN in neuropathic pain are induced through microglial inhibition and the underlying mechanisms. In this study, we observed that SIN alleviated chronic constriction injury (CCI)–induced pain hypersensitivity, spinal microglial activation and neuroinflammation. Consistently, SIN evoked the upregulation of transforming growth factor‐beta1 (TGF‐β1) and phosphorylated Smad3 in the L4–6 ipsilateral spinal dorsal horn of CCI mice. Intrathecal injection of TGF‐β1 siRNA and an activin receptor‐like receptor (ALK5) inhibitor reversed SIN's antinociceptive and antimicroglial effects on CCI mice. Moreover, targeting Smad3 in vitro with siRNA dampened the inhibitory effect of TGF‐β1 on lipopolysaccharide‐induced microglial activation. Finally, targeting Smad3 abrogated SIN‐induced pain relief and microglial inhibition in CCI mice. These findings indicate that the TGF‐β1/ALK5/Smad3 axis plays a key role in the antinociceptive effects of SIN on neuropathic pain, indicating its suppressive ability on microglia.

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Sinomenine Ameliorated Microglial Activation and Neuropathic Pain After Chronic Constriction Injury Via TGF‐β1/ALK5/Smad3 Signalling Pathway

Ling,

Luo,

Yin

et al. 2024

J Cellular Molecular Medi

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Research Progress on Treating Spinal Cord Injury by Modulating the Phenotype of Microglia

Yu,

Cai,

Liu

et al. 2024

J. Integr. Neurosci.

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Spinal cord injury (SCI) is a severe central nervous system disorder with no currently available effective treatment. Microglia are immune cells in the central nervous system that play crucial roles in the SCI occurrence, development, and recovery stages. They exhibit dynamic polarization over time and can switch between classical activation (M1) and alternative activation (M2) phenotypes to respond to environmental stimuli. The M1 phenotype is involved in initiating and sustaining inflammatory responses, while the M2 phenotype exerts anti-inflammatory effects and promotes tissue repair in damaged areas. Inhibiting M1 polarization and promoting M2 polarization have become hotspots in regulating neuroinflammation and treating SCI. This article provides a comprehensive review centered on modulating microglial polarization phenotypes for SCI treatment.

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Transforming Growth Factor β1 Ameliorates Microglial Activation in Perioperative Neurocognitive Disorders

Cited by 2 publications

References 53 publications

Sinomenine Ameliorated Microglial Activation and Neuropathic Pain After Chronic Constriction Injury Via TGF‐β1/ALK5/Smad3 Signalling Pathway

Sinomenine Ameliorated Microglial Activation and Neuropathic Pain After Chronic Constriction Injury Via TGF‐β1/ALK5/Smad3 Signalling Pathway

Research Progress on Treating Spinal Cord Injury by Modulating the Phenotype of Microglia

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