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Chunk #1 — Background

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Neuroinflammation and M2 microglia: the good, the bad, and the inflamed.
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In agreement with Hortega’s original description, microglia have been classically described to exist in two states, resting and activated. However, this binary definition has since been revised to make way for more complex ideas. Microglia in the healthy CNS are not truly ‘resting’. Two-photon microscopy has shown microglia to be engaged in environmental surveillance, constantly sampling areas around them in efforts to maintain homeostasis [4]. Once microglia encounter a substance that they sense is foreign or indicative of harm, they enter an ‘activated’ state. As macrophage-like cells of the brain, one of the main roles of activated microglia is that of regulating CNS innate immunity and initiating appropriate responses, such as inflammation. In the brain, this inflammatory response, termed neuroinflammation, is a fundamental response generated to protect the CNS; however, uncontrolled or prolonged neuroinflammation is potentially harmful and can result in cellular damage. This is particularly relevant to neurodegenerative diseases, which are typified by evidence of microglial activation and neuroinflammation [5]. This makes microglial activation an attractive target to study as part of disease pathogenesis.