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Abstract
Background and Aims: Microglia are the innate immune cells of central nervous system which play critical roles in brain homeostasis. Recently, the effects of general anesthetic agents (GAAs) on microglia and their potential neurotoxicity in neurodevelopment have attracted the attention of anesthesiologists and neuroscientists.
Methods: Here, we review the physiology of microglia in neurodevelopment, the potential mechanisms of GAAs on microglia and the consequent changes in microglial function.
Outcomes: Microglia-mediated neuroinflammation is a key mechanism of neurocognitive deficits during neurodevelopment. In addition, microglia could be primed by active inflammatory processes and have innate immune memory, both of which make them a potential candidate responsible of long-term neural deficits.
Conclusion: This review aims in summarizing the in vivo and in vitro studies associating microglia with general anesthesia and describing how GAAs induce neurocognitive deficits via microglia to further explore the effects of GAAs on neurodevelopment.
Keywords
general anaesthetic agents
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microglia
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neurocognitive deficits
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neurodevelopment
/
neuroinflammation
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Xinyue Liang, Fang Fang, Xiaoqing Wang, Ming Jiang, Jing Cang.
The role ofmicroglia in neurocognitive deficits induced by general anaesthetic agents during neurodevelopment.
Clinical and Translational Discovery, 2024, 4(6): e70012 DOI:10.1002/ctd2.70012
| [1] |
YanJ, JiangH. Dual effects of ketamine: neurotoxicity versus neuroprotection in anesthesia for the developing brain. J Neurosurg Anesthesiol. 2014;26(2):155-160.
|
| [2] |
ClausenNG, HansenTG, DismaN. Anesthesia neurotoxicity in the developing brain: basic studies relevant for neonatal or perinatal medicine. Clin Perinatol. 2019;46(4):647-656.
|
| [3] |
EndresM, MoroMA, NolteCH, et al. Immune pathways in etiology, acute phase, and chronic sequelae of ischemic stroke. Circ Res. 2022;130(8):1167-1186.
|
| [4] |
CorpsKN, RothTL, McgavernDB. Inflammation and neuroprotection in traumatic brain injury. JAMA Neurol. 2015;72(3):355-362.
|
| [5] |
EscoubasCC, Molofsky AV. Microglia as integrators of brain-associated molecular patterns. Trends Immunol. 2024;45(5):358-370.
|
| [6] |
LawrenceAR, CanziA, BridlanceC, et al. Microglia maintain structural integrity during fetal brain morphogenesis. Cell. 2024;187(4):962-980.e19.
|
| [7] |
BaudO, Saint-Faust M. Neuroinflammation in the developing brain: risk factors, involvement of microglial cells, and implication for early anesthesia. Anesth Analg. 2019;128(4):718-725.
|
| [8] |
YangY, HangW, LiJ, et al. Effect of general anesthetic agents on microglia. Aging Dis. 2024;15(3):1308-1328.
|
| [9] |
AguzziA, BarresBA, BennettML. Microglia: scapegoat, saboteur, or something else? Science. 2013;339(6116):156-161.
|
| [10] |
ThionMS, Ginhoux F, GarelS. Microglia and early brain development: an intimate journey. Science. 2018;362(6411):185-189.
|
| [11] |
HoeffelG, Ginhoux F. Fetal monocytes and the origins of tissue-resident macrophages. Cell Immunol. 2018;330:5-15.
|
| [12] |
Marin-TevaJL, Almendros A, CalventeR, et al. Tangential migration of ameboid microglia in the developing quail retina: mechanism of migration and migratory behavior. Glia. 1998;22(1):31-52.
|
| [13] |
Sanchez-LopezAM, Cuadros MA, CalventeR, et al. Activation of immature microglia in response to stab wound in embryonic quail retina. J Comp Neurol. 2005;492(1):20-33.
|
| [14] |
SwinnenN, Smolders S, AvilaA, et al. Complex invasion pattern of the cerebral cortex bymicroglial cells during development of the mouse embryo. Glia. 2013;61(2):150-163.
|
| [15] |
WangH, HeY, SunZ, et al. Microglia in depression: an overview of microglia in the pathogenesis and treatment of depression. J Neuroinflammation. 2022;19(1):132.
|
| [16] |
NakagawaY, ChibaK. Role of microglial m1/m2 polarization in relapse and remission of psychiatric disorders and diseases. Pharmaceuticals. 2014;7(12):1028-1048.
|
| [17] |
TangY, LeW. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol Neurobiol. 2016;53(2):1181-1194.
|
| [18] |
NeherJJ, Cunningham C. Priming microglia for innate immune memory in the brain. Trends Immunol. 2019;40(4):358-374.
|
| [19] |
DattaM, Staszewski O, RaschiE, et al. Histone deacetylases 1 and 2 regulate microglia function during development, homeostasis, and neurodegeneration in a context-dependent manner. Immunity. 2018;48(3):514-529.e6.
|
| [20] |
NayakD, RothTL, McgavernDB. Microglia development and function. Annu Rev Immunol. 2014;32:367-402.
|
| [21] |
TakahashiK, Rochford CD, NeumannH. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J Exp Med. 2005;201(4):647-657.
|
| [22] |
StevensB, AllenNJ, VazquezLE, et al. The classical complement cascade mediates CNS synapse elimination. Cell. 2007;131(6):1164-1178.
|
| [23] |
HollowayRK, Ireland G, SullivanG, et al. Microglial inflammasome activation drives developmental white matter injury. Glia. 2021;69(5):1268-1280.
|
| [24] |
RusinD, Vahl Becirovic L, LyszczarzG, et al. Microglia-derived insulin-like growth factor 1 is critical for neurodevelopment. Cells. 2024;13(2):184.
|
| [25] |
FantinA, VieiraJM, GestriG, et al. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood. 2010;116(5):829-840.
|
| [26] |
FavuzziE, HuangS, SaldiGA, et al. GABA-receptive microglia selectively sculpt developing inhibitory circuits. Cell. 2021;184(15):4048-4063.
|
| [27] |
BadimonA, Strasburger HJ, AyataP, et al. Negative feedback control of neuronal activity by microglia. Nature. 2020;586(7829):417-423.
|
| [28] |
LiuYU, YingY, LiY, et al. Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling. Nat Neurosci. 2019;22(11):1771-1781.
|
| [29] |
HaruwakaK, YingY, LiangY, et al. Microglia enhance post-anesthesia neuronal activity by shielding inhibitory synapses. Nat Neurosci. 2024;27(3):449-461.
|
| [30] |
HuY, HuXD, HeZQ, et al. Anesthesia/surgery activate MMP9 leading to blood-brain barrier disruption, triggering neuroinflammation and POD-like behavior in aged mice. Int Immunopharmacol. 2024;135:112290.
|
| [31] |
ZhangY, GaoY, YangF, et al. Neuroglobin alleviates the neurotoxicity of sevoflurane to fetal rats by inhibiting neuroinflammation and affecting microglial polarization. Brain Res Bull. 2022;183:142-152.
|
| [32] |
PeiZ, WangS, LiQ. Sevoflurane suppresses microglial M2 polarization. Neurosci Lett. 2017;655:160-165.
|
| [33] |
ZhangZ, BaiH, MaX, et al. Blockade of the NLRP3/caspase-1 axis attenuates ketamine-induced hippocampus pyroptosis and cognitive impairment in neonatal rats. J Neuroinflammation. 2021;18(1):239.
|
| [34] |
TangXL, WangX, FangG, et al. Resveratrol ameliorates sevoflurane-induced cognitive impairment by activating the SIRT1/NF-kappaB pathway in neonatal mice. J Nutr Biochem. 2021;90:108579.
|
| [35] |
Rodriguez-GomezJA, Kavanagh E, Engskog-VlachosP, et al. Microglia: agents of the CNS pro-inflammatory response. Cells. 2020;9(7):1717.
|
| [36] |
SaijoK, WinnerB, CarsonCT, et al. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell. 2009;137(1):47-59.
|
| [37] |
HanVX, PatelS, JonesHF, et al. Maternal immune activation and neuroinflammation in human neurodevelopmental disorders. Nat Rev Neurol. 2021;17(9):564-579.
|
| [38] |
BehlT, MakkarR, SehgalA, et al. Current trends in neurodegeneration: cross talks between oxidative stress, cell death, and inflammation. Int J Mol Sci. 2021;22(14):7432.
|
| [39] |
CornellJ, Salinas S, HuangHY, et al. Microglia regulation of synaptic plasticity and learning and memory. Neural Regen Res. 2022;17(4):705-716.
|
| [40] |
SenMK, MahnsDA, CoorssenJR, et al. The roles of microglia and astrocytes in phagocytosis and myelination: insights from the cuprizone model of multiple sclerosis. Glia. 2022;70(7):1215-1250.
|
| [41] |
Candelario-JalilE, Dijkhuizen RM, MagnusT. Neuroinflammation, stroke, blood-brain barrier dysfunction, and imaging modalities. Stroke. 2022;53(5):1473-1486.
|
| [42] |
PenningDH, CazacuS, BrodieA, et al. Neuron-glia crosstalk plays a major role in the neurotoxic effects of ketamine via extracellular vesicles. Front Cell Dev Biol. 2021;9:691648.
|
| [43] |
ShenX, DongY, XuZ, et al. Selective anesthesia-induced neuroinflammation in developing mouse brain and cognitive impairment. Anesthesiology. 2013;118(3):502-515.
|
| [44] |
WangF, LiC, ShaoJ, et al. Sevoflurane induces inflammation of microglia in hippocampus of neonatal rats by inhibiting Wnt/beta-Catenin/CaMKIV pathway. J Pharmacol Sci. 2021;146(2):105-115.
|
| [45] |
GuiL, LeiX, ZuoZ. Decrease of glial cell-derived neurotrophic factor contributes to anesthesia-and surgery-induced learning and memory dysfunction in neonatal rats. J Mol Med. 2017;95(4):369-379.
|
| [46] |
XuLL, XieJQ, ShenJJ, et al. Neuron-derived exosomes mediate sevoflurane-induced neurotoxicity in neonatal mice via transferring lncRNA Gas5 and promoting M1 polarization of microglia. Acta Pharmacol Sin. 2024;45(2):298-311.
|
| [47] |
ZhangL, ZhangJ, YangL, et al. Isoflurane and sevoflurane increase interleukin-6 levels through the nuclear factor-kappa B pathway in neuroglioma cells. Br J Anaesth. 2013;110 Suppl 1(1):i82-i91.
|
| [48] |
JiangT, XuS, ShenY, et al. Genistein attenuates isoflurane-induced neuroinflammation by inhibiting TLR4-mediated microglial-polarization in vivo and in vitro. J Inflamm Res. 2021;14:2587-2600.
|
| [49] |
Linnartz-GerlachB, Schuy C, ShahrazA, et al. Sialylation of neurites inhibits complement-mediated macrophage removal in a human macrophage-neuron co-culture system. Glia. 2016;64(1):35-47.
|
| [50] |
WangG, LiuHY, MengXW, et al. Complement C1q-mediated microglial synaptic elimination by enhancing desialylation underlies sevoflurane-induced developmental neurotoxicity. Cell Biosci. 2024;14(1):42.
|
| [51] |
LiH, ZhouB, LiaoP, et al. Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior. Front Neurol. 2023;14:1142739.
|
| [52] |
KrokenRA, LobergEM, DronenT, et al. A critical review of pro-cognitive drug targets in psychosis: convergence on myelination and inflammation. Front Psychiatry. 2014;5:11.
|
| [53] |
ZhangL, XueZ, LiuQ, et al. Disrupted folate metabolism with anesthesia leads to myelination deficits mediated by epigenetic regulation of ERMN. EBioMedicine. 2019;43:473-486.
|
| [54] |
LiW, MengX, PengK, et al. Boosting microglial lipid metabolism via TREM2 signaling by biomimetic nanoparticles to attenuate the sevoflurane-induced developmental neurotoxicity. Adv Sci. 2024;11(10):e2305989.
|
| [55] |
ChangY, LeeJJ, HsiehCY, et al. Inhibitory effects of ketamine on lipopolysaccharide-induced microglial activation. Mediators Inflamm. 2009;2009:705379.
|
| [56] |
YuG, DymondM, YuanL, et al. Propofol’s effects on phagocytosis, proliferation, nitrate production, and cytokine secretion in pressure-stimulated microglial cells. Surgery. 2011;150(5):887-896.
|
| [57] |
GuiB, SuM, ChenJ, et al. Neuroprotective effects of pretreatment with propofol in LPS-induced BV-2 microglia cells: role of TLR4 and GSK-3beta. Inflammation. 2012;35(5):1632-1640.
|
| [58] |
PengX, LiC, YuW, et al. Propofol attenuates hypoxia-induced inflammation in BV2 microglia by inhibiting oxidative stress and NF-kappaB/Hif-1alpha signaling. Biomed Res Int. 2020;2020:8978704.
|
| [59] |
ChengL, ChenZ, WangL, et al. Propofol partially attenuates complete Freund’s adjuvant-induced neuroinflammation through inhibition of the ERK1/2/NF-kappaB pathway. J Cell Biochem. 2019;120(6):9400-9408.
|
| [60] |
XueH, ZhangYH, GaoQS, et al. Sevoflurane post-conditioning ameliorates neuronal deficits and axon demyelination after neonatal hypoxic ischemic brain injury: role of microglia/macrophage. Cell Mol Neurobiol. 2021;41(8):1801-1816.
|
| [61] |
CaiM, SunS, WangJ, et al. Sevoflurane preconditioning protects experimental ischemic stroke by enhancing anti-inflammatory microglia/macrophages phenotype polarization through GSK-3beta/Nrf2 pathway. CNS Neurosci Ther. 2021;27(11):1348-1365.
|
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2024 The Author(s). Clinical and Translational Discovery published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.