Role of microglia in CNS inflammation

Abstract

There is increasing confusion about the meaning of the terms inflammation, neuroinflammation, and microglial inflammation. We aim in this review to achieve greater clarity regarding these terms, which are essential for our understanding of the role of microglia in CNS inflammatory conditions. The important concept of sterile inflammation is explained against the backdrop of classical inflammation, and its key differences from what researchers refer to when they use the terms neuroinflammation and microglial inflammation are illustrated. We propose to replace the term “neuroinflammation” with “microglial activation” or “CNS pseudo‐inflammation”, if microglial activation does not suffice. In addition, we recommend abandoning the terms “microglial inflammation” and “inflamed microglia” because of the lack of a clear concept behind them.

Angiogenic Factors and Cytokines in Diabetic Retinopathy

“…This classically activated phenotype includes production of inflammatory cytokines, proteases, nitric oxide (NO • ) and reactive oxygen species (ROS). Thus, fully activated microglia can actually cause neuronal death [167,170]. With the concept that macrophages can adopt a range of inflammatory (M1), anti-inflammatory and reparative (M2) phenotypes also came to the realization that microglial activation is not one-dimensional.…”

“…Because microglia are inherently hypersensitive to tissue damage and infection, it is generally presumed that microglia initiate neuroinflammation and that other glial cells respond to and amplify these responses [110,166]. It has been proposed that neuroinflammation should simply be described as "microglial activation," or perhaps as neural "pseudo-inflammation" because astrocytes, as well as microglia, become activated and produce inflammatory mediators [167]. In fact, neuroinflammation is not synonymous with microglial activation, but microglial activation is the main mechanism by which neuroinflammation is instigated in response to nervous tissue perturbations.…”

Neural inflammation and the microglial response in diabetic retinopathy

“…Microglia are key players in the initiation and resolution of neural inflammation. In fact, it has been argued that neural inflammation would be better described as "microglial activation" or perhaps as neural "pseudo-inflammation" in appreciation of the fact that astrocytes, as well as microglia, can also become activated and produce inflammatory mediators [4]. Considerable evidence suggests that microglia become altered in experimental models of diabetic retinopathy (DR), and it was hypothesized that microglial activation may trigger neuronal death and vascular dysfunction in DR [5].…”

“…The term microglial activation initially referred to the process whereby microglia react to detection of diseased tissue or infection by reversion to a macrophage-like phenotype with an amoeboid morphology, increased phagocytic activity, and production of inflammatory interleukins, cytokines, chemokines, proteases, nitric oxide (NO•), and reactive oxygen species. In fact, fully activated microglia can actually cause neuronal death [4,33]. Given that microglia with altered morphologies invariable coincide with acute neural damage and neurodegeneration, it was surmised that they are detrimental and that inflammatory microglial activation represented an opportune therapeutic target for neuroprotection [33].…”

Modulation of Immunity and the Inflammatory Response: A New Target for Treating Drug-resistant Epilepsy

“…In the immunity and inflammatory response associated with epilepsy, the active cells include the microglia (the resident macrophages of the brain), the astrocytes and the neurons, which are only marginally or not at all involved by endotoxemia [76]. Microglia is part of a major class of glial cells and are a part of the brain’s immune system [77].…”