Astragalus polysaccharide (APS) exerts protective effect against acute ischemic stroke (AIS) through enhancing M2 micoglia polarization by regulating adenosine triphosphate (ATP)/ purinergic receptor (P2X7R) axis

Jia, Xiang; Xie, Liying; Liu, Yuan; Tian-fu, Liu; Yang, Peiqun; Hu, Jing; Peng, Zhichao; Luo, Kangrui; Du, Min; Chen, Chao-Jun

doi:10.1080/21655979.2021.1980176

Cited by 17 publications

(6 citation statements)

References 44 publications

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“…The depletion of extracellular Ca 2+ also significantly inhibits cell death, indicating that OGD induces Ca 2+ -dependent microglia cell death [284]. Further in vivo studies performed on a middle cerebral artery occlusion rat model showed that inhibition of P2X7R expression by promoting degradation of ATP protects against the brain injury produced by OGD [285]. However, P2X7Rs are not the sole contributors to the purine-and calcium-dependent ischemic cell death and other mechanisms remain to be discovered.…”

Section: Oxygen Glucose Deprivationmentioning

confidence: 99%

Modulation of Microglial Function by ATP-Gated P2X7 Receptors: Studies in Rat, Mice and Human

Tewari,

Michalski,

Egan

2024

Cells

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P2X receptors are a family of seven ATP-gated ion channels that trigger physiological and pathophysiological responses in a variety of cells. Five of the family members are sensitive to low concentrations of extracellular ATP, while the P2X6 receptor has an unknown affinity. The last subtype, the P2X7 receptor, is unique in requiring millimolar concentrations to fully activate in humans. This low sensitivity imparts the agonist with the ability to act as a damage-associated molecular pattern that triggers the innate immune response in response to the elevated levels of extracellular ATP that accompany inflammation and tissue damage. In this review, we focus on microglia because they are the primary immune cells of the central nervous system, and they activate in response to ATP or its synthetic analog, BzATP. We start by introducing purinergic receptors and then briefly consider the roles that microglia play in neurodevelopment and disease by referencing both original works and relevant reviews. Next, we move to the role of extracellular ATP and P2X receptors in initiating and/or modulating innate immunity in the central nervous system. While most of the data that we review involve work on mice and rats, we highlight human studies of P2X7R whenever possible.

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Section: Oxygen Glucose Deprivationmentioning

confidence: 99%

Modulation of Microglial Function by ATP-Gated P2X7 Receptors: Studies in Rat, Mice and Human

Tewari,

Michalski,

Egan

2024

Cells

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“…Additionally, studies also showed that P2X7R could serve as a potential molecular target for positron emission tomography (PET) imaging of M1 microglia 71–73 . In the context of brain injury‐induced inflammation, P2X7R is linked to rat microglial M1/M2 polarization regulation 74 . Moreover, in the chronic compression injury of the sciatic nerve (CCI) model, microglia were polarized to the M1 type and P2X7R expression was increased 75 .…”

Section: P2x7r Regulates the Activation And Polarization States Of Mi...mentioning

confidence: 99%

“… 71 , 72 , 73 In the context of brain injury‐induced inflammation, P2X7R is linked to rat microglial M1/M2 polarization regulation. 74 Moreover, in the chronic compression injury of the sciatic nerve (CCI) model, microglia were polarized to the M1 type and P2X7R expression was increased. 75 Similarly, P2X7R mediated activated microglia toward the M1 phenotype in cancer‐induced bone pain.…”

Section: P2x7r Regulates the Activation And Polarization Sta...mentioning

confidence: 99%

Involvement of microglial P2X7 receptor in pain modulation

Zhang,

Gao,

Zhang

et al. 2023

CNS Neurosci Ther

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BackgroundPain is a rapid response mechanism that compels organisms to retreat from the harmful stimuli and triggers a repair response. Nonetheless, when pain persists for extended periods, it can lead to adverse changes into in the individual’s brain, negatively impacting their emotional state and overall quality of life. Microglia, the resident immune cells in the central nervous system (CNS), play a pivotal role in regulating a variety of pain‐related disorders. Specifically, recent studies have shed light on the central role that microglial purinergic ligand‐gated ion channel 7 receptor (P2X7R) plays in regulating pain. In this respect, the P2X7R on microglial membranes represents a potential therapeutic target.AimsTo expound on the intricate link between microglial P2X7R and pain, offering insights into potential avenues for future research.MethodsWe reviewed 140 literature and summarized the important role of microglial P2X7R in regulating pain, including the structure and function of P2X7R, the relationship between P2X7R and microglial polarization, P2X7R‐related signaling pathways, and the effects of P2X7R antagonists on pain regulation.ResultsP2X7R activation is related to M1 polarization of microglia, while suppressing P2X7R can transfer microglia from M1 into M2 phenotype. And targeting the P2X7R‐mediated signaling pathways helps to explore new therapy for pain alleviation. P2X7R antagonists also hold potential for translational and clinical applications in pain management.ConclusionsMicroglial P2X7R holds promise as a potential novel pharmacological target for clinical treatments due to its distinctive structure, function, and the development of antagonists.

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“…As the most important pathophysiological feature of ischemic stroke, cerebral blood flow occlusion results in the deficiency of oxygen and glucose, ultimately leading to energy failure and metabolic disorders, as well as a series of secondary pathophysiological changes ( Kunz et al, 2010 #368; Hossain et al, 2014 ; #369). Stimulators in ischemic areas such as ROS, extracellular ATP, and NO mediate the chemotaxis and activation of microglia ( Tian et al, 2016 #370; Jia et al, 2022 #371; Li T. et al, 2022 #372). Reprogramming of the microglial metabolic profile mediates changes in the microglial phenotype, thereby affecting microglial immune function during cerebral ischemia.…”

Section: Interaction Between Microglial Autophagy and Other Biologica...mentioning

confidence: 99%

Microglial autophagy in cerebrovascular diseases

Chen

Zhang

Chu

et al. 2022

Front. Aging Neurosci.

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Microglia are considered core regulators for monitoring homeostasis in the brain and primary responders to central nervous system (CNS) injuries. Autophagy affects the innate immune functions of microglia. Recently some evidence suggests that microglial autophagy is closely associated with brain function in both ischemic stroke and hemorrhagic stroke. Herein, we will discuss the interaction between autophagy and other biological processes in microglia under physiological and pathological conditions and highlight the interaction between microglial metabolism and autophagy. In the end, we focus on the effect of microglial autophagy in cerebrovascular diseases.

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Astragalus polysaccharide (APS) exerts protective effect against acute ischemic stroke (AIS) through enhancing M2 micoglia polarization by regulating adenosine triphosphate (ATP)/ purinergic receptor (P2X7R) axis

Cited by 17 publications

References 44 publications

Modulation of Microglial Function by ATP-Gated P2X7 Receptors: Studies in Rat, Mice and Human

Modulation of Microglial Function by ATP-Gated P2X7 Receptors: Studies in Rat, Mice and Human

Involvement of microglial P2X7 receptor in pain modulation

Microglial autophagy in cerebrovascular diseases

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