ArticleAutophagy2023
Microglial phagocytosis dysfunction in stroke is driven by energy depletion and induction of autophagy.
Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Surgical protocol and ischemic duration determine myeloid cell features and locomotor deficits in preclinical transient middle cerebral artery occlusion.Experimental neurology · 2026Article
- Integrated analysis of single-cell and transcriptome data reveals temporal dynamics of microglial phagocytic reprogramming in neuropathic pain progression.Scientific reports · 2026Article
- Lipid metabolism, microglia, and stroke.Neural regeneration research · 2026Article
- GPNMB regulates EGFR mitochondrial translocation via HK2, influencing microglial respiratory chain and metabolic defects to promote polarization and stroke progression.Cell biology and toxicology · 2026Article
- Ginsenoside Rg1 alleviates post-ischemic stroke neuroinflammation by inhibiting CKLF1-mediated suppression of dead/dying neuron clearance.Acta pharmaceutica Sinica. B · 2026Article
- Single-nucleus brain transcriptomics reveals microglia dysfunction in multiple system atrophy.Nature communications · 2026Article
- Nitric Oxide Donor Alleviates Cardiac Arrest Induced Blood Brain Barrier Injury by Inhibiting HMGB1-ATG5 Mediated Endothelial Autophagy.Cellular and molecular neurobiology · 2026Article
- Phagocytosis and neuroinflammation: orchestrating central nervous system homeostasis, repair, and the resolution of inflammation.Trends in neurosciences · 2026Review
- Microglia-Neuron Crosstalk: An Intimate Molecular Conversation in Neurodegeneration.International journal of molecular sciences · 2026Review
- Migrasomes in Ischemic Stroke: Molecular Landscape and Pathophysiological Impact.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microglial handling of myelin debris and remyelination after ischaemic stroke: recognition, intracellular processing, lipid fate, and oligodendroglial repair.Frontiers in cellular neuroscience · 2026Review
- Neuraminidase A controls pneumococcal recognition and fate: deficiency enhances immune sensing and intracellular survival, while treatment promotes phagocytic clearance.Immunotherapy advances · 2026Article
- ACE2 Alleviates Microglia Neuroinflammation by RANK-RANKL-OPG Axis in Parkinson's Disease.Inflammation · 2025Article
- The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases.Progress in neurobiology · 2025Review
- Injury to repair: Functions of microglia and monocyte-derived cells in ischemic stroke.Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · 2025Review
- Upregulation of adenosine AMolecular psychiatry · 2025Article
- Chemerin 15 enhances microglial phagocytosis to attenuate cerebral ischemia-reperfusion injury through the ChemR23/p38 MAPK pathway.iScience · 2025Article
- Neutrophil Mobilization Triggers Microglial Functional Change to Exacerbate Cerebral Ischemia-Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- XPR1 promotes ovarian cancer growth and regulates MHC-I through autophagy.Genes & diseases · 2025Article
- CKLF1 disrupts microglial efferocytosis following acute ischemic stroke by binding to phosphatidylserine.Cell death and differentiation · 2025Article
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
Microglial phagocytosis of apoptotic debris prevents buildup damage of neighbor neurons and inflammatory responses. Whereas microglia are very competent phagocytes under physiological conditions, we report their dysfunction in mouse and preclinical monkey models of stroke (macaques and marmosets) by transient occlusion of the medial cerebral artery (tMCAo). By analyzing recently published bulk and single cell RNA sequencing databases, we show that the phagocytosis dysfunction was not explained by transcriptional changes. In contrast, we demonstrate that the impairment of both engulfment and degradation was related to energy depletion triggered by oxygen and nutrient deprivation (OND), which led to reduced process motility, lysosomal exhaustion, and the induction of a protective macroautophagy/autophagy response in microglia. Basal autophagy, in charge of removing and recycling intracellular elements, was critical to maintain microglial physiology, including survival and phagocytosis, as we determined both in vivo and in vitro using pharmacological and transgenic approaches. Notably, the autophagy inducer rapamycin partially prevented the phagocytosis impairment induced by tMCAo in vivo but not by OND in vitro, where it even had a detrimental effect on microglia, suggesting that modulating microglial autophagy to optimal levels may be a hard to achieve goal. Nonetheless, our results show that pharmacological interventions, acting directly on microglia or indirectly on the brain environment, have the potential to recover phagocytosis efficiency in the diseased brain. We propose that phagocytosis is a therapeutic target yet to be explored in stroke and other brain disorders and provide evidence that it can be modulated in vivo using rapamycin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.