{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:35:50Z","timestamp":1790202950777,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32471229"],"award-info":[{"award-number":["32471229"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271914"],"award-info":[{"award-number":["82271914"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["KFJN2550"],"award-info":[{"award-number":["KFJN2550"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Large Instruments Open Foundation of Nantong University","award":["32471229"],"award-info":[{"award-number":["32471229"]}]},{"name":"Large Instruments Open Foundation of Nantong University","award":["82271914"],"award-info":[{"award-number":["82271914"]}]},{"name":"Large Instruments Open Foundation of Nantong University","award":["KFJN2550"],"award-info":[{"award-number":["KFJN2550"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>High-altitude cognitive impairment (HACI) results from acute or chronic exposure to hypoxic conditions. Brain lipid homeostasis is crucial for cognitive function, and lipid droplet (LD) accumulation in glia cells is linked to cognitive decline in aging and stroke. However, whether high-altitude exposure affects brain lipid homeostasis is unclear. Microglia, key regulators of brain homeostasis and inflammation, play a significant role in pathological cognitive impairment and are implicated in LD formation. This study investigates whether lipid dysregulation contributes to HACI and explores microglia-driven mechanisms and potential interventions. Mice were exposed to a simulated 7000 m altitude for 48 h, followed by a week of recovery. Cognitive function and LD accumulation in brain cells were assessed. Microglia were depleted using PLX5622, and mice were exposed to hypoxia or lipopolysaccharide (LPS) to validate microglia\u2019s role in driving astrocytic LD accumulation and cognitive decline. Minocycline was used to inhibit inflammation. In vitro, co-culture systems of microglia and astrocytes were employed to confirm microglia-derived pro-inflammatory factors\u2019 role in astrocytic LD accumulation. Hypobaric hypoxia exposure induced persistent cognitive impairment and LD accumulation in hippocampal astrocytes and microglia. Microglia depletion alleviated cognitive deficits and reduced astrocytic LD accumulation. Hypoxia or LPS did not directly cause LD accumulation in astrocytes but activated microglia to release IL-1\u03b2, inducing astrocytic LD accumulation. Microglia depletion also mitigated LPS-induced cognitive impairment and astrocytic LD accumulation. Minocycline reduced hypoxia-induced LD accumulation in co-cultured astrocytes and improved cognitive function. Hypoxia triggers pro-inflammatory microglial activation, leading to LD accumulation and the release of IL-1\u03b2, which drives astrocytic LD accumulation and neuroinflammation, exacerbating HACI. Minocycline effectively restores brain lipid homeostasis and mitigates cognitive impairment. This study provides novel insights into HACI mechanisms and suggests potential therapeutic strategies.<\/jats:p>","DOI":"10.3390\/antiox14080918","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T14:50:03Z","timestamp":1753714203000},"page":"918","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pro-Inflammatory Microglia Exacerbate High-Altitude-Induced Cognitive Impairment by Driving Lipid Droplet Accumulation in Astrocytes"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4815-3635","authenticated-orcid":false,"given":"Xiaoyang","family":"Fan","sequence":"first","affiliation":[{"name":"Institute of Special Environmental Medicine, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong City 226009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitong","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Special Environmental Medicine, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong City 226009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Special Environmental Medicine, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong City 226009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Special Environmental Medicine, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong City 226009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6172-7148","authenticated-orcid":false,"given":"Xueting","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Special Environmental Medicine, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong City 226009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.rce.2019.12.013","article-title":"Acute, subacute and chronic mountain sickness","volume":"221","author":"Garrido","year":"2021","journal-title":"Rev. Clin. Esp."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Koester-Hegmann, C., Bengoetxea, H., Kosenkov, D., Thiersch, M., Haider, T., Gassmann, M., and Schneider Gasser, E.M. (2018). High-Altitude Cognitive Impairment Is Prevented by Enriched Environment Including Exercise via VEGF Signaling. Front. Cell Neurosci., 12.","DOI":"10.3389\/fncel.2018.00532"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40101-014-0039-x","article-title":"Cognitive and psychomotor responses to high-altitude exposure in sea level and high-altitude residents of Ecuador","volume":"34","author":"Davis","year":"2015","journal-title":"J. Physiol. Anthr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e70059","DOI":"10.1111\/cns.70059","article-title":"Decreased cold-inducible RNA-binding protein (CIRP) binding to GluRl on neuronal membranes mediates memory impairment resulting from prolonged hypobaric hypoxia exposure","volume":"30","author":"Jiang","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chen, X., Zhang, J., Lin, Y., Li, Y., Wang, H., Wang, Z., Liu, H., Hu, Y., and Liu, L. (2023). Mechanism, prevention and treatment of cognitive impairment caused by high altitude exposure. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1191058"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1152\/japplphysiol.00861.2019","article-title":"High-altitude cerebral edema: Its own entity or end-stage acute mountain sickness?","volume":"131","author":"Turner","year":"2021","journal-title":"J. Appl. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s13041-021-00827-1","article-title":"Cirbp-PSD95 axis protects against hypobaric hypoxia-induced aberrant morphology of hippocampal dendritic spines and cognitive deficits","volume":"14","author":"Zhou","year":"2021","journal-title":"Mol. Brain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1089\/ham.2018.0066","article-title":"Possible Role of Glymphatic System of the Brain in the Pathogenesis of High-Altitude Cerebral Edema","volume":"19","author":"Simka","year":"2018","journal-title":"High. Alt. Med. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.2147\/JIR.S415695","article-title":"Progress in the Treatment of High Altitude Cerebral Edema: Targeting REDOX Homeostasis","volume":"16","author":"Li","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"154240","DOI":"10.1016\/j.phymed.2022.154240","article-title":"Rhodiola crenulate alleviates hypobaric hypoxia-induced brain injury via adjusting NF-kappaB\/NLRP3-mediated inflammation","volume":"103","author":"Xie","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s12192-023-01386-1","article-title":"Protective effects of epigallocatechin-3-gallate counteracting the chronic hypobaric hypoxia-induced myocardial injury in plain-grown rats at high altitude","volume":"28","author":"Chen","year":"2023","journal-title":"Cell Stress Chaperones"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0022-2275(20)39619-X","article-title":"Lipid composition of the normal human brain: Gray matter, white matter, and myelin","volume":"6","author":"Sampson","year":"1965","journal-title":"J. Lipid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"eadc9317","DOI":"10.1126\/sciadv.adc9317","article-title":"Brain lipidomics: From functional landscape to clinical significance","volume":"8","author":"Yoon","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e2306863","DOI":"10.1002\/advs.202306863","article-title":"Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice","volume":"11","author":"Wei","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111321","DOI":"10.1016\/j.brainresbull.2025.111321","article-title":"New insight into the role of altered brain cholesterol metabolism in the pathogenesis of AD: A unifying cholesterol hypothesis and new therapeutic approach for AD","volume":"224","author":"Yang","year":"2025","journal-title":"Brain Res. Bull."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.brainres.2009.07.010","article-title":"The effects of indomethacin on caspases, glutathione level and lipid peroxidation in the newborn rats with hypoxic-ischemic cerebral injury","volume":"1289","author":"Taskin","year":"2009","journal-title":"Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Vacek, L., Dvorak, A., Bechynska, K., Kosek, V., Elkalaf, M., Trinh, M.D., Fiserova, I., Pospisilova, K., Slovakova, L., and Vitek, L. (2022). Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 Myotubes. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.663625"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"O\u2019Brien, K.A., Atkinson, R.A., Richardson, L., Koulman, A., Murray, A.J., Harridge, S.D.R., Martin, D.S., Levett, D.Z.H., Mitchell, K., and Mythen, M.G. (2019). Metabolomic and lipidomic plasma profile changes in human participants ascending to Everest Base Camp. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-38832-z"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Liang, H., Yan, J., and Song, K. (2022). Comprehensive lipidomic analysis reveals regulation of glyceride metabolism in rat visceral adipose tissue by high-altitude chronic hypoxia. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0267513"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1152\/jappl.1996.81.4.1762","article-title":"Acclimatization to 4,300-m altitude decreases reliance on fat as a substrate","volume":"81","author":"Roberts","year":"1996","journal-title":"J. Appl. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/glia.23120","article-title":"Astrocyte lipid metabolism is critical for synapse development and function in vivo","volume":"65","author":"Camargo","year":"2017","journal-title":"Glia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13195-024-01430-x","article-title":"Navigating the metabolic maze: Anomalies in fatty acid and cholesterol processes in Alzheimer\u2019s astrocytes","volume":"16","author":"Zhang","year":"2024","journal-title":"Alzheimers Res. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1126\/science.294.5545.1354","article-title":"CNS synaptogenesis promoted by glia-derived cholesterol","volume":"294","author":"Mauch","year":"2001","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111882","DOI":"10.1016\/j.celrep.2022.111882","article-title":"The lipid transporter ORP2 regulates synaptic neurotransmitter release via two distinct mechanisms","volume":"41","author":"Kroll","year":"2022","journal-title":"Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1002\/1873-3468.12691","article-title":"Hypothalamic lipid-laden astrocytes induce microglia migration and activation","volume":"591","author":"Kwon","year":"2017","journal-title":"FEBS Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1007\/s12035-018-1183-9","article-title":"Lipotoxic Effects of Palmitic Acid on Astrocytes Are Associated with Autophagy Impairment","volume":"56","author":"Boya","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhang, W., Yang, X., Liu, J., Pan, Y., Zhang, M., and Chen, L. (2022). Senescent Phenotype of Astrocytes Leads to Activation of BV2 Microglia and N2a Neuronal Cells Death. Molecules, 27.","DOI":"10.3390\/molecules27185925"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","article-title":"Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain","volume":"23","author":"Marschallinger","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/j.cell.2019.04.001","article-title":"Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity","volume":"177","author":"Ioannou","year":"2019","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1146\/annurev-immunol-082423-041334","article-title":"Central Nervous System Macrophages in Health and Disease","volume":"43","author":"Greter","year":"2025","journal-title":"Annu. Rev. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, X., Xie, Y., Niu, Y., Wan, B., Lu, Y., Luo, Q., and Zhu, L. (2023). CX3CL1\/CX3CR1 signal mediates M1-type microglia and accelerates high-altitude-induced forgetting. Front. Cell Neurosci., 17.","DOI":"10.3389\/fncel.2023.1189348"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.lfs.2017.10.021","article-title":"Mechanism of aquaporin 4 (AQP 4) up-regulation in rat cerebral edema under hypobaric hypoxia and the preventative effect of puerarin","volume":"193","author":"Wang","year":"2018","journal-title":"Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1038\/s41467-019-11674-z","article-title":"Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer\u2019s disease model","volume":"10","author":"Spangenberg","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.2147\/DDDT.S408304","article-title":"Efficacy and Safety of Anlotinib in Overall and Disease-Specific Advanced Gynecological Cancer: A Real-World Study","volume":"17","author":"Hong","year":"2023","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1186\/s12974-023-02931-6","article-title":"Intermittent hypoxia therapy ameliorates beta-amyloid pathology via TFEB-mediated autophagy in murine Alzheimer\u2019s disease","volume":"20","author":"Wang","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yao, D.P., Li, T., Yu, L., Hu, M.X., He, Y., Zhang, R.M., Wu, J.J., Li, S.Y., Kuang, W.H., and Yang, X.F. (2024). Selective degradation of hyperphosphorylated tau by proteolysis-targeting chimeras ameliorates cognitive function in Alzheimer\u2019s disease model mice. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1351792"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wang, X., Chen, G., Wan, B., Dong, Z., Xue, Y., Luo, Q., Wang, D., Lu, Y., and Zhu, L. (2022). NRF1-mediated microglial activation triggers high-altitude cerebral edema. J. Mol. Cell Biol., 14.","DOI":"10.1093\/jmcb\/mjac036"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s13195-024-01489-6","article-title":"Intermittent hypoxia training enhances Abeta endocytosis by plaque associated microglia via VPS35-dependent TREM2 recycling in murine Alzheimer\u2019s disease","volume":"16","author":"Wang","year":"2024","journal-title":"Alzheimers Res. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nature04515","article-title":"Cryopyrin activates the inflammasome in response to toxins and ATP","volume":"440","author":"Mariathasan","year":"2006","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7957","DOI":"10.1038\/s41467-024-51938-x","article-title":"IL-1beta promotes adipogenesis by directly targeting adipocyte precursors","volume":"15","author":"Hofwimmer","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.bbi.2018.06.012","article-title":"DNA binding protein HMGB1 secreted by activated microglia promotes the apoptosis of hippocampal neurons in diabetes complicated with OSA","volume":"73","author":"Shi","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"175137","DOI":"10.1016\/j.ejphar.2022.175137","article-title":"Pharmacological inhibition of mitochondrial division attenuates simulated high-altitude exposure-induced cerebral edema in mice: Involvement of inhibition of the NF-kappaB signaling pathway in glial cells","volume":"929","author":"Lu","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Aboouf, M.A., Thiersch, M., Soliz, J., Gassmann, M., and Schneider Gasser, E.M. (2023). The Brain at High Altitude: From Molecular Signaling to Cognitive Performance. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210179"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1080\/15548627.2023.2213984","article-title":"Impaired lipophagy induced-microglial lipid droplets accumulation contributes to the buildup of TREM1 in diabetes-associated cognitive impairment","volume":"19","author":"Li","year":"2023","journal-title":"Autophagy"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Xin, W., Pan, Y., Wei, W., Gerner, S.T., Huber, S., Juenemann, M., Butz, M., B\u00e4hr, M., Huttner, H.B., and Doeppner, T.R. (2023). TGF-\u03b21 Decreases Microglia-Mediated Neuroinflammation and Lipid Droplet Accumulation in an In Vitro Stroke Model. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417329"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s12974-022-02549-0","article-title":"Nilotinib modulates LPS-induced cognitive impairment and neuroinflammatory responses by regulating P38\/STAT3 signaling","volume":"19","author":"Kim","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lu, Y., Zhou, M., Li, Y., Li, Y., Hua, Y., and Fan, Y. (2021). Minocycline promotes functional recovery in ischemic stroke by modulating microglia polarization through STAT1\/STAT6 pathways. Biochem. Pharmacol., 186.","DOI":"10.1016\/j.bcp.2021.114464"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"110347","DOI":"10.1016\/j.intimp.2023.110347","article-title":"Intranasal administration of lipopolysaccharide reverses chronic stress-induced depression-like behavior in mice by microglial stimulation","volume":"120","author":"Huang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.3233\/JAD-231485","article-title":"Frontal Cortex Lipid Alterations During the Onset of Alzheimer\u2019s Disease","volume":"98","author":"Perez","year":"2024","journal-title":"J. Alzheimers Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s10020-021-00427-8","article-title":"Abnormal lipid droplets accumulation induced cognitive deficits in obstructive sleep apnea syndrome mice via JNK\/SREBP\/ACC pathway but not through PDP1\/PDC pathway","volume":"28","author":"Li","year":"2022","journal-title":"Mol. Med."},{"key":"ref_51","first-page":"6","article-title":"The role of omega-3 polyunsaturated fatty acids in child development","volume":"93","author":"Ozerskaia","year":"2024","journal-title":"Vopr. Pitan."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1016\/j.clnu.2019.10.017","article-title":"Medium-chain triglycerides improved cognition and lipid metabolomics in mild to moderate Alzheimer\u2019s disease patients with APOE4(-\/-): A double-blind, randomized, placebo-controlled crossover trial","volume":"39","author":"Xu","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.semcdb.2020.07.017","article-title":"Lipid metabolism in astrocytic structure and function","volume":"112","author":"Lee","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.plipres.2011.06.002","article-title":"Cholesterol metabolism in neurons and astrocytes","volume":"50","author":"Pfrieger","year":"2011","journal-title":"Prog. Lipid Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrm.2017.107","article-title":"Sphingolipids and their metabolism in physiology and disease","volume":"19","author":"Hannun","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.plefa.2017.05.001","article-title":"Role of polyunsaturated fatty acids in human brain structure and function across the lifespan: An update on neuroimaging findings","volume":"136","author":"McNamara","year":"2018","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1007\/s12264-024-01299-8","article-title":"Melatonin Ameliorates Abnormal Sleep-Wake Behavior via Facilitating Lipid Metabolism in a Zebrafish Model of Parkinson\u2019s Disease","volume":"40","author":"Pang","year":"2024","journal-title":"Neurosci. Bull."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4197","DOI":"10.7150\/thno.84059","article-title":"Preconditioned extracellular vesicles from hypoxic microglia reduce poststroke AQP4 depolarization, disturbed cerebrospinal fluid flow, astrogliosis, and neuroinflammation","volume":"13","author":"Xin","year":"2023","journal-title":"Theranostics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1007\/s11064-022-03611-2","article-title":"Epigallocatechin-3-Gallate Ameliorated Iron Accumulation and Apoptosis and Promoted Neuronal Regeneration and Memory\/Cognitive Functions in the Hippocampus Induced by Exposure to a Chronic High-Altitude Hypoxia Environment","volume":"47","author":"Chen","year":"2022","journal-title":"Neurochem. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"155529","DOI":"10.1016\/j.phymed.2024.155529","article-title":"Rhodiola crenulata alleviates hypobaric hypoxia-induced brain injury by maintaining BBB integrity and balancing energy metabolism dysfunction","volume":"128","author":"Hou","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e27833","DOI":"10.1016\/j.heliyon.2024.e27833","article-title":"Effect of butylphthalide on prevention and treatment of high altitude cerebral edema in rats","volume":"10","author":"Ma","year":"2024","journal-title":"Heliyon"},{"key":"ref_62","first-page":"575","article-title":"Minocycline attenuates hypoxia-inducible factor-1alpha expression correlated with modulation of p53 and AKT\/mTOR\/p70S6K\/4E-BP1 pathway in ovarian cancer: In vitro and in vivo studies","volume":"5","author":"Pourgholami","year":"2015","journal-title":"Am. J. Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ejphar.2011.01.001","article-title":"Minocycline attenuates ischemia-induced ventricular arrhythmias in rats","volume":"654","author":"Hu","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Jiang, S., Ma, Y., Shi, Y., Zou, Y., Yang, Z., Zhi, W., Zhao, Z., Shen, W., Chen, L., and Wu, Y. (2024). Acute exposure of microwave impairs attention process by activating microglial inflammation. Cell Biosci., 14.","DOI":"10.1186\/s13578-023-01162-9"},{"key":"ref_65","first-page":"2989","article-title":"Minocycline alleviates LPS-induced cognitive dysfunction in mice by inhibiting the NLRP3\/caspase-1 pathway","volume":"16","author":"Zhan","year":"2024","journal-title":"Aging"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/s41423-024-01199-x","article-title":"Lipid droplet accumulation mediates macrophage survival and Treg recruitment via the CCL20\/CCR6 axis in human hepatocellular carcinoma","volume":"21","author":"Wang","year":"2024","journal-title":"Cell Mol. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Ding, Y., Gong, W., Zhang, S., Shen, J., Liu, X., Wang, Y., Chen, Y., and Meng, G. (2021). Protective role of sirtuin3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation. Biochem. Pharmacol., 192.","DOI":"10.1016\/j.bcp.2021.114665"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"eadk1168","DOI":"10.1126\/scitranslmed.adk1168","article-title":"Protumoral lipid droplet-loaded macrophages are enriched in human glioblastoma and can be therapeutically targeted","volume":"16","author":"Governa","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Scuto, M., Rampulla, F., Reali, G.M., Span\u00f2, S.M., Trovato Salinaro, A., and Calabrese, V. (2024). Hormetic Nutrition and Redox Regulation in Gut-Brain Axis Disorders. Antioxidant, 13.","DOI":"10.3390\/antiox13040484"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Scuto, M., Majz\u00fanov\u00e1, M., Torcitto, G., Antonuzzo, S., Rampulla, F., Di Fatta, E., and Trovato Salinaro, A. (2024). Functional Food Nutrients, Redox Resilience Signaling and Neurosteroids for Brain Health. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212155"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3955","DOI":"10.1182\/blood-2010-02-266296","article-title":"An antibody against the colony-stimulating factor 1 receptor depletes the resident subset of monocytes and tissue- and tumor-associated macrophages but does not inhibit inflammation","volume":"116","author":"MacDonald","year":"2010","journal-title":"Blood"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/s41586-020-2474-7","article-title":"Microbiota modulate sympathetic neurons via a gut-brain circuit","volume":"583","author":"Muller","year":"2020","journal-title":"Nature"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.tins.2022.01.002","article-title":"Brain cell type-specific cholesterol metabolism and implications for learning and memory","volume":"45","author":"Li","year":"2022","journal-title":"Trends Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Li, L., Zhuang, L., Xu, Z., Jiang, L., Zhai, Y., Liu, D., and Wu, Q. (2024). U-shaped relationship between non-high-density lipoprotein cholesterol and cognitive impairment in Chinese middle-aged and elderly: A cross-sectional study. BMC Public Health, 24.","DOI":"10.1186\/s12889-024-19164-8"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1016\/j.scib.2021.02.018","article-title":"Low levels of low-density lipoprotein cholesterol and cognitive decline","volume":"66","author":"Hua","year":"2021","journal-title":"Sci. Bull."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.bbi.2017.04.013","article-title":"Hypoxia augments LPS-induced inflammation and triggers high altitude cerebral edema in mice","volume":"64","author":"Zhou","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s12974-016-0528-4","article-title":"Systemic pro-inflammatory response facilitates the development of cerebral edema during short hypoxia","volume":"13","author":"Song","year":"2016","journal-title":"J. Neuroinflamm."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/8\/918\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:16:43Z","timestamp":1760033803000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/8\/918"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,26]]},"references-count":77,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["antiox14080918"],"URL":"https:\/\/doi.org\/10.3390\/antiox14080918","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,26]]}}}