Astragaloside IV promotes microglia/macrophages M2 polarization and enhances neurogenesis and angiogenesis through PPARγ pathway after cerebral ischemia/reperfusion injury in rats

Lin, Li; Gan, Haiyan; Jin, Huaqian; Yan, Fang; Yang, Yan; Zhang, Jianping; Hu, Xiaowei; Chu, Lisheng

doi:10.1016/j.intimp.2020.107335

Cited by 83 publications

(45 citation statements)

References 59 publications

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“…VEGF secreted from anti-inflammatory microglia is known to promote angiogenesis following ischemic stroke ( Xie et al, 2013 ). Astragaloside IV (AS-IV) can enhance angiogenesis and functional recovery, at least partially through switching microglia/macrophages toward the anti-inflammatory phenotype in a peroxisome proliferator-activated receptor (PPAR)-γ-dependent manner after cerebral ischemia ( Li et al, 2021 ). Berberine also was shown to promote angiogenesis through modulating anti-inflammatory microglial polarization via the AMPK pathway ( Zhu et al, 2019 ).…”

Section: Microglial Activation With Brain Plasticity After Strokementioning

confidence: 99%

New Insights Into the Roles of Microglial Regulation in Brain Plasticity-Dependent Stroke Recovery

Huang

Ran

et al. 2021

Front. Cell. Neurosci.

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Stroke remains the leading cause of long-term disability worldwide with significant long-term sequelae. However, there is no highly effective treatment to enhance post-stroke recovery despite extensive efforts in exploring rehabilitative therapies. Neurorehabilitation is recognized as the cornerstone of functional restoration therapy in stroke, where treatments are focused on neuroplastic regulation to reverse neural structural disruption and improve neurofunctional networks. Post-stroke neuroplasticity changes begin within hours of symptom onset and reaches a plateau by 3 to 4 weeks within the global brain in animal studies. It plays a determining role in spontaneous stroke recovery. Microglia are immediately activated following cerebral ischemia, which has been found both proximal to the primary ischemic injury and at the remote brain regions which have functional connections to the primary injury area. Microglia exhibit different activation profiles based on the microenvironment and adaptively switch their phenotypes in a spatiotemporal manner in response to brain injuries. Microglial activation coincides with neuroplasticity after stroke, which provides the fundamental base for the microglia-mediated inflammatory responses involved in the entire neural network rewiring and brain repair. Microglial activation exerts important effects on spontaneous recovery after stroke, including structural and functional reestablishment of neurovascular networks, neurogenesis, axonal remodeling, and blood vessel regeneration. In this review, we focus on the crosstalk between microglial activation and endogenous neuroplasticity, with a special focus on the plastic alterations in the whole brain network and their implications for structural and functional restoration after stroke. We then summarize recent advances in the impacts of microglial phenotype polarization on brain plasticity, trying to discuss the potential efficacy of microglia-based extrinsic restorative interventions in promoting post-stroke recovery.

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Section: Microglial Activation With Brain Plasticity After Strokementioning

confidence: 99%

New Insights Into the Roles of Microglial Regulation in Brain Plasticity-Dependent Stroke Recovery

Huang

Ran

et al. 2021

Front. Cell. Neurosci.

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“…As a significant anti-inflammatory cytokine, Tgfb1 signaling plays a critical role in IL-4-induced M2 macrophage activation through co-signaling to Akt, as well as MAPK pathway, manifested by synergic upregulation with IL-4 on Arg1 expression level in an autocrine and/or paracrine fashion (39,40). Another study showed that Compound 1 (astragaloside IV) were associated with promoting microglia polarization to M2 and improve tissue regeneration in peri-infarct regions in a rat cerebral ischemia/reperfusion injury model, which may be mediated by PPARγ pathway (41). The exact molecular mechanism of how Compound 1 and other compounds regulate microglia polarization is to be identified, but our study indicates that the two herbal ingredients Dangshen and Huangqi may contain compounds with immune-modulatory effects.…”

Section: Discussionmentioning

confidence: 99%

Anti-neuroinflammatory activity of Shenqi Fuzheng Injection and its main active constituents

Wang

Zhang

Deng

et al. 2021

BST

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“…Previous reports have demonstrated that anti-inflammatory microglia can enhance BDNF production, promote axon sprouting and preserve myelin integrity [ 12 , 51 , 52 ]. In line with a previous study, our data showed that the inhibition of P2X4R with 5-BDBD can significantly increase BDNF levels by promoting the microglial phenotype to an anti-inflammatory phenotype after ICH.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of P2X4R attenuates white matter injury in mice after intracerebral hemorrhage by regulating microglial phenotypes

Zhou

et al. 2021

J Neuroinflammation

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Background White matter injury (WMI) is a major neuropathological event associated with intracerebral hemorrhage (ICH). P2X purinoreceptor 4 (P2X4R) is a member of the P2X purine receptor family, which plays a crucial role in regulating WMI and neuroinflammation in central nervous system (CNS) diseases. Our study investigated the role of P2X4R in the WMI and the inflammatory response in mice, as well as the possible mechanism of action after ICH. Methods ICH was induced in mice via collagenase injection. Mice were treated with 5-BDBD and ANA-12 to inhibit P2X4R and tropomyosin-related kinase receptor B (TrkB), respectively. Immunostaining and quantitative polymerase chain reaction (qPCR) were performed to detect microglial phenotypes after the inhibition of P2X4R. Western blots (WB) and immunostaining were used to examine WMI and the underlying molecular mechanisms. Cylinder, corner turn, wire hanging, and forelimb placement tests were conducted to evaluate neurobehavioral function. Results After ICH, the protein levels of P2X4R were upregulated, especially on day 7 after ICH, and were mainly located in the microglia. The inhibition of P2X4R via 5-BDBD promoted neurofunctional recovery after ICH as well as the transformation of the pro-inflammatory microglia induced by ICH into an anti-inflammatory phenotype, and attenuated ICH-induced WMI. Furthermore, we found that TrkB blockage can reverse the protective effects of WMI as well as neuroprotection after 5-BDBD treatment. This result indicates that P2X4R plays a crucial role in regulating WMI and neuroinflammation and that P2X4R inhibition may benefit patients with ICH. Conclusions Our results demonstrated that P2X4R contributes to WMI by polarizing microglia into a pro-inflammatory phenotype after ICH. Furthermore, the inhibition of P2X4R promoted pro-inflammatory microglia polarization into an anti-inflammatory phenotype, enhanced brain-derived neurotrophic factor (BDNF) production, and through the BDNF/TrkB pathway, attenuated WMI and improved neurological function. Therefore, the regulation of P2X4R activation may be beneficial for the reducing of ICH-induced brain injury.

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Astragaloside IV promotes microglia/macrophages M2 polarization and enhances neurogenesis and angiogenesis through PPARγ pathway after cerebral ischemia/reperfusion injury in rats

Cited by 83 publications

References 59 publications

New Insights Into the Roles of Microglial Regulation in Brain Plasticity-Dependent Stroke Recovery

New Insights Into the Roles of Microglial Regulation in Brain Plasticity-Dependent Stroke Recovery

Anti-neuroinflammatory activity of Shenqi Fuzheng Injection and its main active constituents

Inhibition of P2X4R attenuates white matter injury in mice after intracerebral hemorrhage by regulating microglial phenotypes

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