Debris clearance by microglia: an essential link between degeneration and regeneration

By H. Neumann, Mark Kotter, Robin J. M. Franklin. Brain : a journal of neurology, 2008

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Microglia are cells of myeloid origin that populate the CNS during early development and form the brain's innate immune cell type. They perform homoeostatic activity in the normal CNS, a function associated with high motility of their ramified processes and their constant phagocytic clearance of cell debris. This debris clearance role is amplified in CNS injury, where there is frank loss of tissue and recruitment of microglia to the injured area. Recent evidence suggests that this phagocytic clearance following injury is more than simply tidying up, but instead plays a fundamental role in facilitating the reorganization of neuronal circuits and triggering repair. Insufficient clearance by microglia, prevalent in several neurodegenerative diseases and declining with ageing, is associated with an inadequate regenerative response. Thus, understanding the mechanism and functional significance of microglial-mediated clearance of tissue debris following injury may open up exciting new therapeutic avenues.

Subfields: Immunology, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/6f325d9d3196574aa95b2eba5f156ced76b36358

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Citations in the corpus

Infiltrating Blood-Derived Macrophages Are Vital Cells Playing an Anti-inflammatory Role in Recovery from Spinal Cord Injury in Mice (2009, background): “It is possible that other beneficial properties of infiltrating MW contribute to the repair process; MW are capable of secreting growth and neurotrophic factors [30– 32,41], phagocytosis and clearance of cell debris [88], degradation of growth-limiting scar tissue [89], and promotion of remyelinatio”
Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s disease (2009, background): “innate immunity and surveillance of the parenchyma [12, 15, 18, 33 , 34].”
Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders (2010, background): “and contribute to an environment that supports neuronal viability and regeneration, and myelin sheath formatio”
Microglial M1/M2 polarization and metabolic states (2016, background): “state is, in part, due to signals derived from neuronal- and astrocyte-derived factors (Cardona et al., 2006; Neumann et al., 2009; Ransohoff and Cardona, 2010).”
Microglial brain region-dependent diversity and selective regional sensitivities to ageing (2016, neutral): “Key findings include that (1) transcriptional networks controlling microglial bioenergetic and immunoregulatory functions contribute prominently to heterogeneity in the young adult, (2) immunophenotypic variation suggests a more immune vigilant state of cerebellar microglia, (3) networks of gene co-”
CSF1 receptor signaling is necessary for microglia viability, which unmasks a cell that rapidly repopulates the microglia-depleted adult brain (2014, neutral): “Morphological analyses of surviving microglia revealed a larger cell body (Figure S2E), an increased thickness of processes (Figure S2F) typically associated with a more phagocytotic phenotype (Neumann et al., 2009), and a reduction in the number of branches per microglia (Figure S2H).”
Interrelation of Oxidative Stress and Inflammation in Neurodegenerative Disease: Role of TNF (2015, background): “This is corroborated by the finding that autophagy is reduced in aging CNS cells [45] and that microglia are less efficiently recruited to the areas of neurodegeneration resulting in delayed tissue repair in the aging CNS [46].”
The Role of Microglia in the Healthy Brain (2011, background): “Postnatal development: microglial phagocytosis of extranumerary synapses The first 2 weeks of postnatal development are a period of remarkable plasticity with new synapses being actively formed and remodeled.”
The biphasic function of microglia in ischemic stroke (2017, positive): “Microglia play a beneficial role for tissue remodeling and regeneration after ischemic stroke via clearing dead or dying neurons (Brown and Neher, 2014; Neumann et al., 2009).”
Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis (2010, background): “Third, phagocytosis of the apoptotic newborn cells is performed exclusively by ‘‘unchallenged’’ microglia, indicating a novel, previously unrecognized role of such microglia in the normal adult SGZ neurogenic niche that has not been acknowledged in recent reviews (Ekdahl et al., 2009; Neumann et al.”
Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications (2021, background): “Since it can reduce inflammation, it is beneficial for dead and dying neurons to undergo phagocytosis.(306,307) Live neurons can also undergo the same process, to result in the death of the engulfed neurons,(308,309) termed phagoptosis.”