Abstract
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.
Highlights
Microglia, resident macrophages in the central nervous system (CNS), are responsible for the clearance of degenerated cells and foreign materials from the CNS via phagocytosis, which establishes their status as immunocompetent cells
Secondary injuries include (1) neuronal damage caused by the excitotoxicity of glutamate released from neurons and microglia; (2) chemical modification of proteins, phospholipids, and nucleic acids in neurons by reactive oxygen species (ROS); (3) neuronal damage caused by excessive inflammation associated with local and systemic immune reactions; (4) neuronal cell death caused by excessive phagocytosis by immune cells
Microglia are deeply involved in the maintenance of homeostasis and play critical roles in both the normal and pathological CNS and peripheral nervous system (PNS)
Summary
Resident macrophages in the central nervous system (CNS), are responsible for the clearance of degenerated cells and foreign materials from the CNS via phagocytosis, which establishes their status as immunocompetent cells Their origin has been a subject of debate for a long time, a fate-mapping analysis revealed that microglia originated from primitive macrophages present in the yolk sac, and not from myeloid cells [1]. We discuss microglia in the spinal cord and macrophages in the injured peripheral nerve These cells modulate the release of pro- and anti-inflammatory cytokines, as in CNS injuries, and engage in both neuroprotective and neurodestructive actions, thereby affecting nerve regeneration and pain behavior. In the final section of this article, we describe therapeutic interventions targeting microglia/macrophages for pathological conditions of both the CNS and PNS
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