Chronic constriction injury of the sciatic nerve in rats causes different activation modes of microglia between the anterior and posterior horns of the spinal cord

Nishihara, Tasuku; Tanaka, Junya; Sekiya, Keizo; Nishikawa, Yuki; Abe, Naoki; Hamada, Taisuke; Kitamura, Sakiko; Ikemune, Keizo; Ochi, Shinichiro; Choudhury, Mohammed E.; Yano, Hajime; Yorozuya, Toshihiro

doi:10.1016/j.neuint.2020.104672

Cited by 23 publications

(22 citation statements)

References 33 publications

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“…The signaling increases the expression of transcription factors such as IRF8 and IRF5, and subsequently induces and maintains neuropathic pain by triggering the expression of receptors, such as P2RX4 and CX3CR1, and cytokines, such as TNFα, IL1β, and BDNF [104]. CD68 and F4/80 in the ventral horn was lower than that in the dorsal horn, suggesting that microglia in the dorsal horn possess stronger phagocytic activity than do those in the ventral horn [44]. The phagocytosis of myelin by microglia in the dorsal horn may be correlated with the development of neuropathic pain.…”

Section: Microglia/macrophages In the Pns Injurymentioning

confidence: 99%

“…Under anaerobic conditions, energy production by OXPHOS becomes impossible, and energy is produced by anaerobic glycolysis while synthesizing lactate. Activated pro-inflammatory microglia and macrophages produce ATP in a glycolysis-dependent manner even under aerobic conditions, and increase lactate production and glucose uptake [42][43][44][45]. This enhanced glycolytic pathway and increased glucose uptake under aerobic conditions are known as the Warburg effect [46].…”

Section: Metabolic Changes In Microglia In Tbi and Infarctionmentioning

confidence: 99%

“…Why is microglial encirclement observed only in the ventral horn motor neurons? Activated microglia in the ventral horn appear to be more neuroprotective than those in the dorsal horn because motor dysfunction starts to ameliorate within three days after the onset of peripheral nerve injury, whereas neuropathic pain persists for much longer periods [44]. If the phenotypic changes that occur in the ventral microglia can be induced in the dorsal microglia, the persistent neuropathic pain may be ameliorated.…”

Section: Microglia/macrophages In the Pns Injurymentioning

confidence: 99%

“…However, their activation mode seems to be different in the ventral and dorsal horns of the spinal cord. In the dorsal horn, microglia exhibit an amoeboid morphology, a classic mode of activation, whereas in the ventral horn, they display an elongated morphology surrounding neurons that appear to engage in synaptic stripping [44]. Synaptic stripping was first reported in a facial nerve injury model in 1968 by Blinzinger et al [106].…”

Section: Immunomodulationmentioning

confidence: 99%

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Microglia and Macrophages in the Pathological Central and Peripheral Nervous Systems

Abe

Nishihara

Yorozuya

et al. 2020

Cells

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Microglia, the immunocompetent cells in the central nervous system (CNS), have long been studied as pathologically deteriorating players in various CNS diseases. However, microglia exert ameliorating neuroprotective effects, which prompted us to reconsider their roles in CNS and peripheral nervous system (PNS) pathophysiology. Moreover, recent findings showed that microglia play critical roles even in the healthy CNS. The microglial functions that normally contribute to the maintenance of homeostasis in the CNS are modified by other cells, such as astrocytes and infiltrated myeloid cells; thus, the microglial actions on neurons are extremely complex. For a deeper understanding of the pathophysiology of various diseases, including those of the PNS, it is important to understand microglial functioning. In this review, we discuss both the favorable and unfavorable roles of microglia in neuronal survival in various CNS and PNS disorders. We also discuss the roles of blood-borne macrophages in the pathogenesis of CNS and PNS injuries because they cooperatively modify the pathological processes of resident microglia. Finally, metabolic changes in glycolysis and oxidative phosphorylation, with special reference to the pro-/anti-inflammatory activation of microglia, are intensively addressed, because they are profoundly correlated with the generation of reactive oxygen species and changes in pro-/anti-inflammatory phenotypes.

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Section: Microglia/macrophages In the Pns Injurymentioning

confidence: 99%

Section: Metabolic Changes In Microglia In Tbi and Infarctionmentioning

confidence: 99%

Section: Microglia/macrophages In the Pns Injurymentioning

confidence: 99%

Section: Immunomodulationmentioning

confidence: 99%

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Microglia and Macrophages in the Pathological Central and Peripheral Nervous Systems

Abe

Nishihara

Yorozuya

et al. 2020

Cells

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“…This model is well known to cause chronic neuropathic pain [62] . Microglia exhibit activated morphology in the posterior horn, and they phagocytose myelin elements [63] . Constriction injury-induced hyperalgesia and the activation of microglia in the posterior horn are sustained chronically.…”

Section: Peripheral Nerve Injurymentioning

confidence: 99%

Favorable and unfavorable roles of microglia and macrophages in the pathologic central nervous system

Tanaka¹

2020

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How to cite this article: Tanaka J. Favorable and unfavorable roles of microglia and macrophages in the pathologic central nervous system. Neuroimmunol Neuroinflammation 2020;7:73-91. http://dx. AbstractResident microglia in the central nervous system (CNS) are activated rapidly in response to even minor pathologic changes in the CNS, releasing various cytokines, growth factors, reactive oxygen species and other bioactive substances, in addition to eliminating synapses and degenerating cells through phagocytosis. Monocytes in circulation invade the inflamed brain tissues and develop into macrophages that also produce several bioactive substances and engage in phagocytosis. This article introduces methods for distinguishing microglia and macrophages. The pathophysiological roles of resident microglia and macrophages are discussed in animal models with neuroinflammation in the brain either with or without disruption of the blood-brain barrier. Both cell types have ameliorating and aggravating effects on the pathologic CNS, and their different roles are addressed in this article. Furthermore, this article compares the effects of some pharmacological interventions to induce phenotypic cellular changes for improved outcomes of the pathologic CNS.

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Sex‐specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury

Fiore

Yin

Güneykaya

et al. 2022

Glia

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Neuropathic pain is a prevalent and debilitating chronic disease that is characterized by activation in glial cells in various pain-related regions within the central nervous system. Recent studies have suggested a sexually dimorphic role of microglia in the maintenance of neuropathic pain in rodents. Here, we utilized RNA sequencing analysis and in vitro primary cultures of microglia to identify whether there is a common neuropathic microglial signature and characterize the sex differences in microglia in pain-related regions in nerve injury and chemotherapy-induced peripheral neuropa-

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Chronic constriction injury of the sciatic nerve in rats causes different activation modes of microglia between the anterior and posterior horns of the spinal cord

Cited by 23 publications

References 33 publications

Microglia and Macrophages in the Pathological Central and Peripheral Nervous Systems

Microglia and Macrophages in the Pathological Central and Peripheral Nervous Systems

Favorable and unfavorable roles of microglia and macrophages in the pathologic central nervous system

Sex‐specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury

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