Microglial phagocytosis [Neurosurgery Wiki]

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====== Microglial phagocytosis ======

[[Microglia]] are brain professional [[phagocyte]]s mainly finalized to [[clearance]] of apoptotic or necrotic cells
((Green DR, Oguin TH, Martinez J. The clearance of dying cells: table for two. Cell Death Differ. 2016 Jun;23(6):915-26. doi: 10.1038/cdd.2015.172. Epub 2016 Mar 18. PMID: 26990661; PMCID: PMC4987729.)).
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[[Stroke]], including [[ischemic stroke]] and [[hemorrhagic stroke]], can cause massive [[neuronal death]] and disruption of the brain [[structure]], which is followed by secondary inflammatory injury initiated by pro-inflammatory molecules and cellular debris. Phagocytic clearance of cellular [[debris]] by [[microglia]], the brain's scavenger cells, is pivotal for [[neuroinflammation]] resolution and neurorestoration. However, [[microglia]] can also exacerbate neuronal loss by phagocytosing stressed-but-viable [[neuron]]s in the [[penumbra]], thereby expanding the [[injury]] area and hindering neurofunctional [[recovery]]. Microglia constantly patrol the central nervous system using their processes to scour the cellular environment and start or cease the phagocytosis progress depending on the "eat me" or "don't eat me'' signals on the cellular surface. An optimal immune response requires a delicate balance between different phenotypic states to regulate neuroinflammation and facilitate reconstruction after stroke
((Chen W, Zhang Y, Zhai X, Xie L, Guo Y, Chen C, Li Y, Wang F, Zhu Z, Zheng L, Wan J, Li P. Microglial phagocytosis and regulatory mechanisms after stroke. J Cereb Blood Flow Metab. 2022 May 1:271678X221098841. doi: 10.1177/0271678X221098841. Epub ahead of print. PMID: 35491825.)).
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Zhao et al. demonstrated that elevated [[mTOR]] signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippocampal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes. Moreover, the mice thus affected develop severe early-onset spontaneous recurrent seizures (SRSs). Therefore, we have revealed an epileptogenic mechanism that is independent of the microglial inflammatory response. Our data suggest that microglia could be an opportune target for epilepsy prevention
((Zhao X, Liao Y, Morgan S, Mathur R, Feustel P, Mazurkiewicz J, Qian J, Chang
J, Mathern GW, Adamo MA, Ritaccio AL, Gruenthal M, Zhu X, Huang Y.
Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy. Cell Rep. 
2018 Feb 20;22(8):2080-2093. doi: 10.1016/j.celrep.2018.02.004. PubMed PMID:
29466735.
)).