247
Views
0
CrossRef citations to date
0
Altmetric
REVIEW

Progress in the Treatment of High Altitude Cerebral Edema: Targeting REDOX Homeostasis

, , , , , , , , ORCID Icon & show all
Pages 2645-2660 | Received 04 Apr 2023, Accepted 15 Jun 2023, Published online: 23 Jun 2023

References

  • Márquez MF. The heart at high altitude. Trends Cardiovasc Med. 2022;2022:e15.
  • Pena E, El Alam S, Siques P, Brito J. Oxidative stress and diseases associated with high-altitude exposure. Antioxidants. 2022;11(2):267.
  • Luks AM, Auerbach PS, Freer L, et al. Wilderness medical society clinical practice guidelines for the prevention and treatment of acute altitude illness: 2019 update. Wilderness Environ Med. 2019;30(4s):S3–s18.
  • Biller A, Badde S, Heckel A, et al. Exposure to 16 h of normobaric hypoxia induces ionic edema in the healthy brain. Nat Commun. 2021;12(1):5987.
  • Chen Y, He Y, Zhao S, He X, Xue D, Xia Y. Hypoxic/ischemic inflammation, microRNAs and δ-opioid receptors: hypoxia/ischemia-sensitive versus-insensitive organs. Front Aging Neurosci. 2022;14:847374.
  • Jensen JD, Vincent AL. High Altitude Cerebral Edema. Treasure Island (FL): StatPearls Publishing; 2022.
  • Zelmanovich R, Pierre K, Felisma P, Cole D, Goldman M, Lucke-Wold B. High altitude cerebral edema: improving treatment options. Biologics. 2022;2(1):81–91.
  • Sawicka M, Szymczak RK. A fatal case of high-altitude cerebral oedema on a climbing expedition to Karakoram. Travel Med Infect Dis. 2022;2022:102493.
  • Hao GS, Fan QL, Hu QZ, Hou Q. Research progress on the mechanism of cerebral blood flow regulation in hypoxia environment at plateau. Bioengineered. 2022;13(3):6353–6358.
  • Murray AJ, Montgomery HE, Feelisch M, Grocott MPW, Martin DS. Metabolic adjustment to high-altitude hypoxia: from genetic signals to physiological implications. Biochem Soc Trans. 2018;46(3):599–607.
  • Jing L, Wu N, Zhang J, Da Q, Ma H. Protective effect of 5,6,7,8-Tetrahydroxyflavone on high altitude cerebral edema in rats. Eur J Pharmacol. 2022;928:175121.
  • Mrakic-Sposta S, Montorsi M, Porcelli S, et al. Effects of prolonged exposure to hypobaric hypoxia on oxidative stress: overwintering in antarctic concordia station. Oxid Med Cell Longev. 2022;2022:4430032.
  • Chiang S, Braidy N, Maleki S, Lal S, Richardson DR, Huang ML. Mechanisms of impaired mitochondrial homeostasis and NAD(+) metabolism in a model of mitochondrial heart disease exhibiting redox active iron accumulation. Redox Biol. 2021;46:102038.
  • Checconi P, De Angelis M, Marcocci ME, et al. Redox-modulating agents in the treatment of viral infections. Int J Mol Sci. 2020;21(11):154.
  • Fraternale A, Zara C, De Angelis M, et al. Intracellular redox-modulated pathways as targets for effective approaches in the treatment of viral infection. Int J Mol Sci. 2021;22(7):e245.
  • Arslanbaeva LR, Santoro MM. Adaptive redox homeostasis in cutaneous melanoma. Redox Biol. 2020;37:101753.
  • Li H, Fu X, Yao F, Tian T, Wang C, Yang A. MTHFD1L-mediated redox homeostasis promotes tumor progression in tongue squamous cell carcinoma. Front Oncol. 2019;9:1278.
  • Kubli SP, Bassi C, Roux C. AhR controls redox homeostasis and shapes the tumor microenvironment in BRCA1-associated breast cancer. Proc Natl Acad Sci U S A. 2019;116(9):3604–3613.
  • Shao D, Oka S, Brady CD, Haendeler J, Eaton P, Sadoshima J. Redox modification of cell signaling in the cardiovascular system. J Mol Cell Cardiol. 2012;52(3):550–558.
  • He X, Liu J, Zang WJ. Mitochondrial homeostasis and redox status in cardiovascular diseases: protective role of the vagal system. Free Radic Biol Med. 2022;178:369–379.
  • Paspalj D, Nikic P, Savic M, et al. Redox status in acute ischemic stroke: correlation with clinical outcome. Mol Cell Biochem. 2015;406(1–2):75–81.
  • Eleftheriadou D, Kesidou D, Moura F, Felli E, Song W. Redox-responsive nanobiomaterials-based therapeutics for neurodegenerative diseases. Small. 2020;16(43):e1907308.
  • Akanji MA, Rotimi DE, Elebiyo TC, Awakan OJ, Adeyemi OS. Redox homeostasis and prospects for therapeutic targeting in neurodegenerative disorders. Oxid Med Cell Longev. 2021;2021:9971885.
  • Cao XF, Bai ZZ, Ma L, Ma S, Ge RL. Metabolic alterations of qinghai-tibet plateau pikas in adaptation to high altitude. High Alt Med Biol. 2017;18(3):219–225.
  • Gangwar A, Paul S, Ahmad Y, Bhargava K. Intermittent hypoxia modulates redox homeostasis, lipid metabolism associated inflammatory processes and redox post-translational modifications: benefits at high altitude. Sci Rep. 2020;10(1):7899.
  • Ni Q, Shao Y, Wang YZ, Jing YH, Zhang YC. Impact of high altitude on the hepatic fatty acid oxidation and synthesis in rats. Biochem Biophys Res Commun. 2014;446(2):574–579.
  • Gao WX, Wu G, Gao YQ. Pathophysiological changes in mitochondria of mammalian exposed to hypoxia at high altitude. Chin j Appl Physiol. 2014;30(6):502–505.
  • Canouï-Poitrine F, Veerabudun K, Larmignat P, Letournel M, Bastuji-Garin S, Richalet JP. Risk prediction score for severe high altitude illness: a cohort study. PLoS One. 2014;9(7):e100642.
  • Higgins JP, Tuttle T, Higgins JA. Altitude and the heart: is going high safe for your cardiac patient? Am Heart J. 2010;159(1):25–32.
  • Falla M, Giardini G, Angelini C. Recommendations for traveling to altitude with neurological disorders. J Central Nervous Syst Dis. 2021;13:11795735211053448.
  • Xue Y, Wang X, Wan B, et al. Caveolin-1 accelerates hypoxia-induced endothelial dysfunction in high-altitude cerebral edema. Cell Commun Signal. 2022;20(1):160.
  • Pu X, Li F, Lin X, Wang R, Chen Z. Oxidative stress and expression of inflammatory factors in lung tissue of acute mountain sickness rats. Mol Med Rep. 2022;25(2):85.
  • Liu B, Chen J, Zhang L, et al. IL-10 dysregulation in acute mountain sickness revealed by transcriptome analysis. Front Immunol. 2017;8:628.
  • Zhou Y, Huang X, Zhao T, et al. Hypoxia augments LPS-induced inflammation and triggers high altitude cerebral edema in mice. Brain Behav Immun. 2017;64:266–275.
  • Wang X, Chen G, Wan B, et al. NRF1-mediated microglial activation triggers high-altitude cerebral edema. J Mol Cell Biol. 2022;22:121.
  • Song TT, Bi YH, Gao YQ, et al. Systemic pro-inflammatory response facilitates the development of cerebral edema during short hypoxia. J Neuroinflammation. 2016;13(1):63.
  • Bajinka O, Simbilyabo L, Tan Y, Jabang J, Saleem SA. Lung-brain axis. Crit Rev Microbiol. 2022;48(3):257–269.
  • Li C, Chen W, Lin F, et al. Functional two-way crosstalk between brain and lung: the brain-lung axis. Cell Mol Neurobiol. 2022;2022:1–13.
  • Riech S, Kallenberg K, Moerer O, et al. The pattern of brain microhemorrhages after severe lung failure resembles the one seen in high-altitude cerebral edema. Crit Care Med. 2015;43(9):e386–9.
  • Sharma S, Singh Y, Sandhir R, et al. Mitochondrial DNA mutations contribute to high altitude pulmonary edema via increased oxidative stress and metabolic reprogramming during hypobaric hypoxia. Biochimica et Biophysica Acta Bioenergetics. 2021;1862(8):148431.
  • Mishra A, Ali Z, Vibhuti A, et al. CYBA and GSTP1 variants associate with oxidative stress under hypobaric hypoxia as observed in high-altitude pulmonary oedema. Clin Sci. 2012;122(6):299–309.
  • Ugalde JM, Aller I, Kudrjasova L, et al. Endoplasmic reticulum oxidoreductin provides resilience against reductive stress and hypoxic conditions by mediating luminal redox dynamics. Plant Cell. 2022;2022:147.
  • Sasidharan R, Schippers JHM, Schmidt RR. Redox and low-oxygen stress: signal integration and interplay. Plant Physiol. 2021;186(1):66–78.
  • Mallet RT, Burtscher J, Pialoux V, et al. Molecular mechanisms of high-altitude acclimatization. Int J Mol Sci. 2023;24(2):221.
  • Hackett PH, Roach RC. High-altitude illness. N Engl J Med. 2001;345(2):107–114.
  • Savioli G, Ceresa IF, Gori G, et al. Pathophysiology and therapy of high-altitude sickness: practical approach in emergency and critical care. J Clin Med. 2022;11(14):26.
  • Wu T, Ding S, Liu J, et al. Ataxia: an early indicator in high altitude cerebral edema. High Alt Med Biol. 2006;7(4):275–280.
  • Hackett PH, Yarnell PR, Hill R, Reynard K, Heit J, McCormick J. High-altitude cerebral edema evaluated with magnetic resonance imaging: clinical correlation and pathophysiology. JAMA. 1998;280(22):1920–1925.
  • Bailey DM, Bärtsch P, Knauth M, Baumgartner RW. Emerging concepts in acute mountain sickness and high-altitude cerebral edema: from the molecular to the morphological. Cell Mol Life Sci. 2009;66(22):3583–3594.
  • Li N, Chen K, Bai J, et al. Tibetan medicine Duoxuekang ameliorates hypobaric hypoxia-induced brain injury in mice by restoration of cerebrovascular function. J Ethnopharmacol. 2021;270:113629.
  • Xie Y, Yang D, Huang AS, et al. Retinal microvasculature is a potential biomarker for acute mountain sickness. Sci China Life Sci. 2023;2023:187.
  • Willmann G, Gekeler F, Schommer K, Bärtsch P. Update on high altitude cerebral edema including recent work on the eye. High Alt Med Biol. 2014;15(2):112–122.
  • Molano Franco D, Nieto Estrada VH, Gonzalez Garay AG, Martí-Carvajal AJ, Arevalo-Rodriguez I. Interventions for preventing high altitude illness: part 3. Miscellaneous and non-pharmacological interventions. Cochrane Database Sys Rev. 2019;4(4):Cd013315.
  • Davis C, Hackett P. Advances in the prevention and treatment of high altitude illness. Emerg Med Clin North Am. 2017;35(2):241–260.
  • Clark ST, Sheraton M. EMS High-Altitude Field Prophylaxis and Treatment. Treasure Island (FL): StatPearls Publishing; 2022.
  • Gao D, Wang Y, Zhang R, Zhang Y. Efficacy of Acetazolamide for the prophylaxis of acute mountain sickness: a systematic review, meta-analysis, and trial sequential analysis of randomized clinical trials. Ann Thorac Med. 2021;16(4):337–346.
  • Murata T, Suzuki N, Yamawaki H, et al. Dexamethasone prevents impairment of endothelium-dependent relaxation in arteries cultured with fetal bovine serum. Eur J Pharmacol. 2005;515(1–3):134–141.
  • Szymczak RK, Sawicka M. Can intranasal delivery of dexamethasone facilitate the management of severe altitude disease? J Travel Med. 2023;2023:78.
  • Johnson NJ, Luks AM. High-altitude medicine. Med Clin North Am. 2016;100(2):357–369.
  • Luo QQ, Yang JX, Zhang XM. The protective effects of ginkgolide B and hypoxic preconditioning against acute hypoxia injury in mice. Chin J Appl Physiol. 2009;25(3):362–365.
  • Jiang S, Fan F, Yang L, et al. Salidroside attenuates high altitude hypobaric hypoxia-induced brain injury in mice via inhibiting NF-κB/NLRP3 pathway. Eur J Pharmacol. 2022;925:175015.
  • Patir H, Sarada SK, Singh S, Mathew T, Singh B, Bansal A. Quercetin as a prophylactic measure against high altitude cerebral edema. Free Radic Biol Med. 2012;53(4):659–668.
  • Dong YS, Wang JL, Feng DY, et al. Protective effect of quercetin against oxidative stress and brain edema in an experimental rat model of subarachnoid hemorrhage. Int J Med Sci. 2014;11(3):282–290.
  • Li X, Cheng Z, Chen X, Yang D, Li H, Deng Y. Purpurogallin improves neurological functions of cerebral ischemia and reperfusion mice by inhibiting endoplasmic reticulum stress and neuroinflammation. Int Immunopharmacol. 2022;111:109057.
  • Wang C, Yan M, Jiang H, et al. Mechanism of aquaporin 4 (AQP 4) up-regulation in rat cerebral edema under hypobaric hypoxia and the preventative effect of puerarin. Life Sci. 2018;193:270–281.
  • Wang C, Yan M, Jiang H, et al. Protective effects of puerarin on acute lung and cerebrum injury induced by hypobaric hypoxia via the regulation of aquaporin (AQP) via NF-κB signaling pathway. Int Immunopharmacol. 2016;40:300–309.
  • Chen G, Cheng K, Niu Y, Zhu L, Wang X. (-)-Epicatechin gallate prevents inflammatory response in hypoxia-activated microglia and cerebral edema by inhibiting NF-κB signaling. Arch Biochem Biophys. 2022;2022:109393.
  • Huo Y, Zhao A, Song J, Li J, Wang R. 槟榔多酚对急进高原大鼠具有抗缺氧作用 [Betelnut polyphenols provide protection against high-altitude hypoxia in rats]. J Southern Med Univ. 2021;41(5):671–678. Chinese.
  • Le Gal K, Schmidt EE, Sayin VI. Cellular redox homeostasis. Antioxidants. 2021;10(9):24.
  • Wang X, Li S, Liu Y, Ma C. Redox regulated peroxisome homeostasis. Redox Biol. 2015;4:104–108.
  • Solaini G, Baracca A, Lenaz G, Sgarbi G. Hypoxia and mitochondrial oxidative metabolism. Biochim Biophys Acta. 2010;1797:1171–7.
  • Lee IG, Lee BJ. How bacterial redox sensors transmit redox signals via structural changes. Antioxidants. 2021;10(4):224.
  • Wu R, Li S, Hudlikar R, et al. Redox signaling, mitochondrial metabolism, epigenetics and redox active phytochemicals. Free Radic Biol Med. 2022;179:328–336.
  • Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020;21(7):363–383.
  • Santos LR, Rebelato E, Graciano MF, Abdulkader F, Curi R, Carpinelli AR. Oleic acid modulates metabolic substrate channeling during glucose-stimulated insulin secretion via NAD(P)H oxidase. Endocrinology. 2011;152(10):3614–3621.
  • Shadel GS, Horvath TL. Mitochondrial ROS signaling in organismal homeostasis. Cell. 2015;163(3):560–569.
  • Yee C, Yang W, Hekimi S. The intrinsic apoptosis pathway mediates the pro-longevity response to mitochondrial ROS in C. elegans. Cell. 2014;157(4):897–909.
  • Ježek P. Mitochondrial redox regulations and redox biology of mitochondria. Antioxidants. 2021;10(12):21.
  • Ciccarese F, Ciminale V. Escaping death: mitochondrial redox homeostasis in cancer cells. Front Oncol. 2017;7:117.
  • Wang CH, Wei YH. Roles of mitochondrial sirtuins in mitochondrial function, redox homeostasis, insulin resistance and type 2 diabetes. Int J Mol Sci. 2020;21(15):54.
  • Van Aken O. Mitochondrial redox systems as central hubs in plant metabolism and signaling. Plant Physiol. 2021;186(1):36–52.
  • Baneke A. What role does the blood brain barrier play in acute mountain sickness? Travel Med Infect Dis. 2010;8(4):257–262.
  • Huang X, Zhou Y, Zhao T, et al. A method for establishing the high-altitude cerebral edema (HACE) model by acute hypobaric hypoxia in adult mice. J Neurosci Methods. 2015;245:178–181.
  • Farías JG, Herrera EA, Carrasco-Pozo C, et al. Pharmacological models and approaches for pathophysiological conditions associated with hypoxia and oxidative stress. Pharmacol Ther. 2016;158:1–23.
  • Fuhrmann DC, Brüne B. Mitochondrial composition and function under the control of hypoxia. Redox Biol. 2017;12:208–215.
  • Behn C, Araneda OF, Llanos AJ, Celedón G, González G. Hypoxia-related lipid peroxidation: evidences, implications and approaches. Respir Physiol Neurobiol. 2007;158(2–3):143–150.
  • Wilson MH, Newman S, Imray CH. The cerebral effects of ascent to high altitudes. Lancet Neurol. 2009;8(2):175–191.
  • Bogdanova A, Petrushanko IY, Hernansanz-Agustín P, Martínez-Ruiz A. ”Oxygen Sensing” by Na,K-ATPase: these miraculous thiols. Front Physiol. 2016;7:314.
  • Oechmichen M, Meissner C. Cerebral hypoxia and ischemia: the forensic point of view: a review. J Forensic Sci. 2006;51(4):880–887.
  • Luo Y, Yang X, Gao Y. Mitochondrial DNA response to high altitude: a new perspective on high-altitude adaptation. Mitochondrial DNA. 2013;24(4):313–319.
  • Purushothaman J, Suryakumar G, Shukla D, et al. Modulatory effects of seabuckthorn (Hippophae rhamnoides L.) in hypobaric hypoxia induced cerebral vascular injury. Brain Res Bull. 2008;77(5):246–252.
  • Himadri P, Kumari SS, Chitharanjan M, Dhananjay S. Role of oxidative stress and inflammation in hypoxia-induced cerebral edema: a molecular approach. High Alt Med Biol. 2010;11(3):231–244.
  • Gong G, Yin L, Yuan L, et al. Ganglioside GM1 protects against high altitude cerebral edema in rats by suppressing the oxidative stress and inflammatory response via the PI3K/AKT-Nrf2 pathway. Mol Immunol. 2018;95:91–98.
  • Jing L, Wu N, He L, Shao J, Ma H. Establishment of an experimental rat model of high altitude cerebral edema by hypobaric hypoxia combined with temperature fluctuation. Brain Res Bull. 2020;165:253–262.
  • Sun ZL, Jiang XF, Cheng YC, et al. Exendin-4 inhibits high-altitude cerebral edema by protecting against neurobiological dysfunction. Neural Regeneration Res. 2018;13(4):653–663.
  • Lin H, Chang CP, Lin HJ, Lin MT, Tsai CC. Attenuating brain edema, hippocampal oxidative stress, and cognitive dysfunction in rats using hyperbaric oxygen preconditioning during simulated high-altitude exposure. J Trauma Acute Care Surg. 2012;72(5):1220–1227.
  • Wang X, Hou Y, Li Q, et al. Rhodiola crenulata attenuates apoptosis and mitochondrial energy metabolism disorder in rats with hypobaric hypoxia-induced brain injury by regulating the HIF-1α/microRNA 210/ISCU1/2(COX10) signaling pathway. J Ethnopharmacol. 2019;241:111801.
  • Hou Y, Wang X, Chen X, et al. Establishment and evaluation of a simulated high‑altitude hypoxic brain injury model in SD rats. Mol Med Rep. 2019;19(4):2758–2766.
  • Luan F, Li M, Han K, et al. Phenylethanoid glycosides of Phlomis younghusbandii Mukerjee ameliorate acute hypobaric hypoxia-induced brain impairment in rats. Mol Immunol. 2019;108:81–88.
  • Pan Y, Zhang Y, Yuan J, et al. Tetrahydrocurcumin mitigates acute hypobaric hypoxia-induced cerebral oedema and inflammation through the NF-κB/VEGF/MMP-9 pathway. Phytother Res. 2020;34(11):2963–2977.
  • Shi J, Wang J, Zhang J, et al. Polysaccharide extracted from Potentilla anserina L ameliorate acute hypobaric hypoxia-induced brain impairment in rats. Phytother Res. 2020;34(9):2397–2407.
  • Tormos KV, Chandel NS. Inter-connection between mitochondria and HIFs. J Cell Mol Med. 2010;14(4):795–804.
  • Zemtsova I, Görg B, Keitel V, Bidmon HJ, Schrör K, Häussinger D. Microglia activation in hepatic encephalopathy in rats and humans. Hepatology. 2011;54(1):204–215.
  • Haruwaka K, Ikegami A, Tachibana Y, et al. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nat Commun. 2019;10(1):5816.
  • Kang R, Gamdzyk M, Lenahan C, Tang J, Tan S, Zhang JH. The dual role of microglia in blood-brain barrier dysfunction after stroke. Curr Neuropharmacol. 2020;18(12):1237–1249.
  • Thrane AS, Rappold PM, Fujita T, et al. Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited by cerebral edema. Proc Natl Acad Sci U S A. 2011;108(2):846–851.
  • Chausse B, Lewen A, Poschet G, Kann O. Selective inhibition of mitochondrial respiratory complexes controls the transition of microglia into a neurotoxic phenotype in situ. Brain Behav Immun. 2020;88:802–814.
  • Kang TC. Nuclear factor-erythroid 2-related factor 2 (Nrf2) and mitochondrial dynamics/mitophagy in neurological diseases. Antioxidants. 2020. 9:617.
  • Liu S, Pi J, Zhang Q. Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway. Redox Biol. 2022;54:102389.
  • Strom J, Xu B, Tian X, Chen QM. Nrf2 protects mitochondrial decay by oxidative stress. FASEB J. 2016;30(1):66–80.
  • Wang L, Zhang X, Xiong X, et al. Nrf2 regulates oxidative stress and its role in cerebral ischemic stroke. Antioxidants. 2022;11(12):57.
  • Li HS, Zhou YN, Li L, et al. HIF-1α protects against oxidative stress by directly targeting mitochondria. Redox Biol. 2019;25:101109.
  • Cyran AM, Zhitkovich A. HIF1, HSF1, and NRF2: oxidant-responsive trio raising cellular defenses and engaging immune system. Chem Res Toxicol. 2022;35(10):1690–1700.
  • Simka M, Latacz P, Czaja J. Possible role of glymphatic system of the brain in the pathogenesis of high-altitude cerebral edema. High Alt Med Biol. 2018;19(4):394–397.
  • Clément T, Rodriguez-Grande B, Badaut J. Aquaporins in brain edema. J Neurosci Res. 2020;98(1):9–18.
  • Jayakumar AR, Tong XY, Ruiz-Cordero R, et al. Activation of NF-κB mediates astrocyte swelling and brain edema in traumatic brain injury. J Neurotrauma. 2014;31(14):1249–1257.
  • Stokum JA, Kurland DB, Gerzanich V, Simard JM. Mechanisms of astrocyte-mediated cerebral edema. Neurochem Res. 2015;40(2):317–328.
  • Li Y, Zhao P, Gong T, et al. Redox dyshomeostasis strategy for hypoxic tumor therapy based on DNAzyme-loaded electrophilic ZIFs. Angewandte Chemie. 2020;59(50):22537–22543.
  • Li Y, Gong T, Gao H, et al. ZIF-based nanoparticles combine X-ray-induced nitrosative stress with autophagy management for hypoxic prostate cancer therapy. Angewandte Chemie. 2021;60(28):15472–15481.
  • González-Candia A, Candia AA, Paz A, et al. Cardioprotective antioxidant and anti-inflammatory mechanisms induced by intermittent hypobaric hypoxia. Antioxidants. 2022;11(6):59.
  • Botao Y, Ma J, Xiao W, et al. Protective effect of ginkgolide B on high altitude cerebral edema of rats. High Alt Med Biol. 2013;14(1):61–64.
  • Xie N, Fan F, Jiang S, et al. Rhodiola crenulate alleviates hypobaric hypoxia-induced brain injury via adjusting NF-κB/NLRP3-mediated inflammation. Phytomedicine. 2022;103:154240.
  • Yan X, Liu J, Zhu M, et al. Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness. Pharm Biol. 2021;59(1):1540–1550.
  • Geng Y, Yang J, Cheng X, et al. A bioactive gypenoside (GP-14) alleviates neuroinflammation and blood brain barrier (BBB) disruption by inhibiting the NF-κB signaling pathway in a mouse high-altitude cerebral edema (HACE) model. Int Immunopharmacol. 2022;107:108675.
  • Lu Y, Chang P, Ding W, et al. Pharmacological inhibition of mitochondrial division attenuates simulated high-altitude exposure-induced cerebral edema in mice: involvement of inhibition of the NF-κB signaling pathway in glial cells. Eur J Pharmacol. 2022;929:175137.
  • Shrivastava K, Shukla D, Bansal A, Sairam M, Banerjee PK, Ilavazhagan G. Neuroprotective effect of cobalt chloride on hypobaric hypoxia-induced oxidative stress. Neurochem Int. 2008;52(3):368–375.
  • Hovsepyan LM, Zakaryan GV, Melkonyan MM, Zakaryan AV. [The effects of taurine on oxidative processes in brain edema]. Zhurnal nevrologii i psikhiatrii imeni S S Korsakova. 2015;115(5):64–67. Russian.
  • Ding Y, Liu J, Xu Y, Dong X, Shao B. Evolutionary adaptation of aquaporin-4 in Yak (Bos grunniens) brain to high-altitude hypoxia of Qinghai-Tibetan plateau. High Alt Med Biol. 2020;21(2):167–175.
  • Fukuda AM, Badaut J. Aquaporin 4: a player in cerebral edema and neuroinflammation. J Neuroinflammation. 2012;9:279.