{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T11:20:56Z","timestamp":1762341656024,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"We acknowledge the Lobachevsky University competitiveness program in the frame of 5-100 Russian Academic Excellence Project. The research was carried out using The Core Facilities \u00abMolecular Biology and Neurophysiology\u00bb of Lobachevsky University.","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The use of vitamin D3 along with traditional therapy opens up new prospects for increasing the adaptive capacity of nerve cells to the effects of a wide range of stress factors, including hypoxia-ischemic processes. However, questions about prophylactic and therapeutic doses of vitamin D3 remain controversial. The purpose of our study was to analyze the effects of vitamin D3 at different concentrations on morpho-functional characteristics of neuron\u2013glial networks in hypoxia modeling in vitro. We showed that a single administration of vitamin D3 at a high concentration (1 \u00b5M) in a normal state has no significant effect on the cell viability of primary neuronal cultures; however, it has a pronounced modulatory effect on the functional calcium activity of neuron\u2013glial networks and causes destruction of the network response. Under hypoxia, the use of vitamin D3 (1 \u00b5M) leads to total cell death of primary neuronal cultures and complete negation of functional neural network activity. In contrast, application of lower concentrations of vitamin D3 (0.01 \u00b5M and 0.1 \u00b5M) caused a pronounced dose-dependent neuroprotective effect during the studied post-hypoxic period. While the use of vitamin D3 at a concentration of 0.1 \u00b5M maintained cell viability, preventive administration of 0.01 \u00b5M not only partially preserved the morphological integrity of primary neuronal cells but also maintained the functional structure and activity of neuron\u2013glial networks in cultures. Possible molecular mechanisms of neuroprotective action of vitamin D3 can be associated with the increased expression level of transcription factor HIF-1\u03b1 and maintaining the relationship between the levels of BDNF and TrkB expression in cells of primary neuronal cultures.<\/jats:p>","DOI":"10.3390\/ijms22115417","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T13:15:15Z","timestamp":1621602915000},"page":"5417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Double-Edged Sword of Vitamin D3 Effects on Primary Neuronal Cultures in Hypoxic States"],"prefix":"10.3390","volume":"22","author":[{"given":"Maria","family":"Loginova","sequence":"first","affiliation":[{"name":"Department of Neurotechnology, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Mishchenko","sequence":"additional","affiliation":[{"name":"Department of Neurotechnology, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Savyuk","sequence":"additional","affiliation":[{"name":"Department of Neurotechnology, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Guseva","sequence":"additional","affiliation":[{"name":"Department of Neurotechnology, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Gavrish","sequence":"additional","affiliation":[{"name":"Department of Neurotechnology, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1169-5149","authenticated-orcid":false,"given":"Mikhail","family":"Krivonosov","sequence":"additional","affiliation":[{"name":"Department of Applied Mathematics, Institute of Information Technologies, Mathematics and Mechanics (ITMM), Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail","family":"Ivanchenko","sequence":"additional","affiliation":[{"name":"Department of Applied Mathematics, Institute of Information Technologies, Mathematics and Mechanics (ITMM), Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-9299","authenticated-orcid":false,"given":"Julia","family":"Fedotova","sequence":"additional","affiliation":[{"name":"Department of Neurotechnology, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"},{"name":"Laboratory of Neuroendocrinology, I.P. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Emb. Makarova, 199034 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Vedunova","sequence":"additional","affiliation":[{"name":"Department of Neurotechnology, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1212\/WNL.54.2.362","article-title":"Hypoxia, hyperoxia, ischemia, and brain necrosis","volume":"54","author":"Miyamoto","year":"2000","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2174\/1570161115666161104095522","article-title":"Apoptosis and Acute Brain Ischemia in Ischemic Stroke","volume":"15","author":"Radak","year":"2017","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s11064-018-2682-9","article-title":"Sevoflurane Postconditioning Inhibits Autophagy through Activation of the Extracellular Signal-Regulated Kinase Cascade, Alleviating Hypoxic-Ischemic Brain Injury in Neonatal Rats","volume":"44","author":"Wang","year":"2019","journal-title":"Neurochem. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"132","DOI":"10.3389\/fcell.2018.00132","article-title":"Reactive Oxygen Species Formation in the Brain at Different Oxygen Levels: The Role of Hypoxia Inducible Factors","volume":"6","author":"Chen","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1159\/000486819","article-title":"Vitamin D and Its Role in Neonatal Hypoxic-Ischemic Brain Injury","volume":"113","author":"Stessman","year":"2018","journal-title":"Neonatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"146430","DOI":"10.1016\/j.brainres.2019.146430","article-title":"Calcitriol alleviates global cerebral ischemia-induced cognitive impairment by reducing apoptosis regulated by VDR\/ERK signaling pathway in rat hippocampus","volume":"1724","author":"Guo","year":"2019","journal-title":"Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s12017-018-8484-z","article-title":"Vitamin D3 Supplementation Reduces Subsequent Brain Injury and Inflammation Associated with Ischemic Stroke","volume":"20","author":"Evans","year":"2018","journal-title":"NeuroMol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.fct.2018.10.054","article-title":"Vitamin D3 deficiency in puberty rats causes presynaptic malfunctioning through alterations in exocytotic release and uptake of glutamate\/GABA and expression of EAAC-1\/GAT-3 transporters","volume":"123","author":"Krisanova","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.3109\/14767058.2015.1081889","article-title":"Status of vitamin D, antioxidant enzymes, and antioxidant substances in neonates with neonatal hypoxic-ischemic encephalopathy","volume":"29","author":"Mutlu","year":"2016","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.neuropharm.2017.06.004","article-title":"Vitamin D improves functional outcomes in neonatal hypoxic ischemic male rats treated with N -acetylcysteine and hypothermia","volume":"123","author":"Lowe","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_11","first-page":"7069","article-title":"Vitamin D3 promotes cerebral angiogenesis after cerebral infarction in rats by activating Shh signaling pathway","volume":"22","author":"Bao","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3652894","DOI":"10.1155\/2019\/3652894","article-title":"Severity of Vitamin D Deficiency Predicts Mortality in Ischemic Stroke Patients","volume":"2019","author":"Wajda","year":"2019","journal-title":"Dis. Markers"},{"key":"ref_13","first-page":"364","article-title":"Vitamin D receptor activation influences the ERK pathway and protects against neurological deficits and neuronal death","volume":"41","author":"Yuan","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1002\/ijc.29519","article-title":"HIF-1 at the crossroads of hypoxia, inflammation, and cancer","volume":"138","author":"Balamurugan","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s10571-012-9803-9","article-title":"Hypoxia Inducible Factor-1: Its Potential Role in Cerebral Ischemia","volume":"32","author":"Singh","year":"2012","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.brainres.2012.06.055","article-title":"Decreased VEGF expression and microvascular density, but increased HIF-1 and 2\u03b1 accumulation and EPO expression in chronic moderate hyperoxia in the mouse brain","volume":"1471","author":"Benderro","year":"2012","journal-title":"Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.brainres.2007.08.059","article-title":"Relationship between HIF-1\u03b1 expression and neuronal apoptosis in neonatal rats with hypoxia\u2013ischemia brain injury","volume":"1180","author":"Li","year":"2007","journal-title":"Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"698","DOI":"10.3122\/jabfm.2009.06.090037","article-title":"Vitamin D: An Evidence-Based Review","volume":"22","author":"Kulie","year":"2009","journal-title":"J. Am. Board Fam. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1600-0625.2010.01202.x","article-title":"Vitamin D: An ancient hormone","volume":"20","author":"Bikle","year":"2011","journal-title":"Exp. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1159\/000486536","article-title":"Vitamin D: Classic and Novel Actions","volume":"72","author":"Gil","year":"2018","journal-title":"Ann. Nutr. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ensci.2018.12.004","article-title":"Neuroprotective role of vitamin D in primary neuronal cortical culture","volume":"14","author":"AlJohri","year":"2019","journal-title":"eNeurologicalSci"},{"key":"ref_22","first-page":"904967","article-title":"Vitamin D and Pain: Vitamin D and Its Role in the Aetiology and Maintenance of Chronic Pain States and Associated Comorbidities","volume":"19","author":"Shipton","year":"2015","journal-title":"Pain Res. Treat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"16041","DOI":"10.1038\/boneres.2016.41","article-title":"Vitamin D, calcium homeostasis and aging","volume":"4","author":"Veldurthy","year":"2016","journal-title":"Bone Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1080\/01616412.2019.1622872","article-title":"Vitamin D and the nervous system","volume":"41","author":"Bivona","year":"2019","journal-title":"Neurol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s11154-017-9424-1","article-title":"The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention","volume":"18","author":"Holick","year":"2017","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1689S","DOI":"10.1093\/ajcn\/80.6.1689S","article-title":"Overview of general physiologic features and functions of vitamin D","volume":"80","author":"DeLuca","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev-nutr-082117-051628","article-title":"Bioavailability of Fat-Soluble Vitamins and Phytochemicals in Humans: Effects of Genetic Variation","volume":"38","author":"Borel","year":"2018","journal-title":"Annu. Rev. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.cupe.2003.08.007","article-title":"Disorders of calcium metabolism","volume":"13","author":"Allgrove","year":"2003","journal-title":"Curr. Paediatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"478","DOI":"10.2174\/1871527318666190703102330","article-title":"Implications of Vitamin D in Multiple Sclerosis and Other Neurodegenerative Processes: Bibliometric Analysis and Systematic Review","volume":"18","author":"Escribano","year":"2019","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s13167-017-0120-8","article-title":"Vitamin D in the prevention, prediction and treatment of neurodegenerative and neuroinflammatory diseases","volume":"8","author":"Koduah","year":"2017","journal-title":"EPMA J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jaut.2019.03.002","article-title":"Immunological effects of vitamin D and their relations to autoimmunity","volume":"100","author":"Yamamoto","year":"2019","journal-title":"J. Autoimmun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.5415\/apallergy.2017.7.2.65","article-title":"The role of vitamin D in allergic rhinitis","volume":"7","author":"Tian","year":"2017","journal-title":"Asia Pac. Allergy"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1530\/EJE-11-0984","article-title":"MECHANISMS IN ENDOCRINOLOGY: Vitamin D and fertility: A systematic review","volume":"166","author":"Lerchbaum","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s11154-016-9405-9","article-title":"Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept","volume":"18","author":"Altieri","year":"2017","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3389\/fendo.2012.00058","article-title":"Vitamin D and Cancer","volume":"3","author":"Vuolo","year":"2012","journal-title":"Front. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s11892-019-1201-y","article-title":"Type 2 Diabetes Mellitus, Insulin Resistance, and Vitamin D","volume":"19","author":"Sacerdote","year":"2019","journal-title":"Curr. Diabetes Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.ecl.2017.07.009","article-title":"Role of Vitamin D in Cardiovascular Diseases","volume":"46","author":"Rai","year":"2017","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Gois, P.H.F., Ferreira, D., Olenski, S., and Seguro, A.C. (2017). Vitamin D and Infectious Diseases: Simple Bystander or Contributing Factor?. Nutrients, 9.","DOI":"10.3390\/nu9070651"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Fedotova, J.O. (2019). Vitamin D3 treatment differentially affects anxiety-like behavior in the old ovariectomized female rats and old ovariectomized female rats treated with low dose of 17\u03b2-estradiol. BMC Med. Genet., 20.","DOI":"10.1186\/s12881-019-0774-2"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"288","DOI":"10.2174\/1570159X17666191108111120","article-title":"Vitamin D and Depression in Women: A Mini-review","volume":"18","author":"Boulkrane","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fedotova, J., Pivina, S., and Sushko, A. (2017). Effects of Chronic Vitamin D3 Hormone Administration on Anxiety-Like Behavior in Adult Female Rats after Long-Term Ovariectomy. Nutrients, 9.","DOI":"10.3390\/nu9010028"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s11011-016-9939-2","article-title":"Vitamin D deficiency is associated with acute ischemic stroke, C-reactive protein, and short-term outcome","volume":"32","author":"Alfieri","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.2147\/CIA.S187142","article-title":"Association between vitamin D status and cognitive impairment in acute ischemic stroke patients: A prospective cohort study","volume":"13","author":"Chen","year":"2018","journal-title":"Clin. Interv. Aging"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000434691","article-title":"Serum Vitamin D Status as a Predictor of Prognosis in Patients with Acute Ischemic Stroke","volume":"40","author":"Park","year":"2015","journal-title":"Cerebrovasc. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Galior, K., Grebe, S., and Singh, R. (2018). Development of Vitamin D Toxicity from Overcorrection of Vitamin D Deficiency: A Review of Case Reports. Nutrients, 10.","DOI":"10.3390\/nu10080953"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.tins.2019.01.003","article-title":"Vitamin D in Synaptic Plasticity, Cognitive Function, and Neuropsychiatric Illness","volume":"42","author":"Mayne","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108671","DOI":"10.1016\/j.abb.2020.108671","article-title":"Peroxiredoxin 1\u2014Multifunctional antioxidant enzyme, protects from oxidative damages and increases the survival rate of mice exposed to total body irradiation","volume":"697","author":"Sharapov","year":"2021","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nrm1009","article-title":"Nongenomic actions of steroid hormones","volume":"4","author":"Wehling","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1523\/JNEUROSCI.21-01-00098.2001","article-title":"Vitamin D Hormone Confers Neuroprotection in Parallel with Downregulation of L-Type Calcium Channel Expression in Hippocampal Neurons","volume":"21","author":"Brewer","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S0028-3908(01)00009-0","article-title":"Protective effects of 1\u03b1,25-(OH)2D3 against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture","volume":"40","author":"Ibi","year":"2001","journal-title":"Neuropharmacology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e925350","DOI":"10.12659\/MSM.925350","article-title":"Vitamin D Attenuates Hypoxia-Induced Injury in Rat Primary Neuron Cells through Downregulation of the Dual Oxidase 1 (DUOX1) Gene","volume":"26","author":"Cui","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.3892\/mmr.2013.1734","article-title":"Neuroprotective effect of calcitriol on ischemic\/reperfusion injury through the NR3A\/CREB pathways in the rat hippocampus","volume":"8","author":"Fu","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"ref_53","first-page":"1","article-title":"Protective effects of vitamin D on neurophysiologic alterations in brain aging: Role of brain-derived neurotrophic factor (BDNF)","volume":"16","author":"Khairy","year":"2019","journal-title":"Nutr. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Koshkina, A., Dudnichenko, T., Baranenko, D., Fedotova, J., and Drago, F. (2019). Effects of Vitamin D3 in Long-Term Ovariectomized Rats Subjected to Chronic Unpredictable Mild Stress: BDNF, NT-3, and NT-4 Implications. Nutrients, 11.","DOI":"10.3390\/nu11081726"},{"key":"ref_55","first-page":"157","article-title":"The Effect of Vitamin D Treatment on Nerve Growth Factor (NGF) Release from Hippocampal Neurons","volume":"51","author":"Dursun","year":"2014","journal-title":"Noro Psikiyatr. Ars."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3389\/fncel.2013.00149","article-title":"Seizure-like activity in hyaluronidase-treated dissociated hippocampal cultures","volume":"7","author":"Vedunova","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"453901","DOI":"10.1155\/2015\/453901","article-title":"TrkB-Mediated Neuroprotective and Antihypoxic Properties of Brain-Derived Neurotrophic Factor","volume":"2015","author":"Vedunova","year":"2015","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Zakharov, Y.N., Mitroshina, E.V., Shirokova, O., and Mukhina, I.V. (2013). Calcium Transient Imaging as Tool for Neuronal and Glial Network Interaction Study, Springer.","DOI":"10.1007\/978-1-4614-5574-5_12"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kustikova, V., Krivonosov, M., Pimashkin, A., Denisov, P., Zaikin, A., Ivanchenko, M., Meyerov, I., and Semyanov, A. (2018). CalciumCV: Computer Vision Software for Calcium Signaling in Astrocytes, Springer International Publishing.","DOI":"10.1007\/978-3-030-11027-7_17"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Savyuk, M., Krivonosov, M., Mishchenko, T., Gazaryan, I., Ivanchenko, M., Khristichenko, A., Poloznikov, A., Hushpulian, D., Nikulin, S., and Tonevitsky, E. (2020). Neuroprotective Effect of HIF Prolyl Hydroxylase Inhibition in an In Vitro Hypoxia Model. Antioxidants, 9.","DOI":"10.3390\/antiox9080662"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/5417\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:05:10Z","timestamp":1760162710000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/5417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,21]]},"references-count":60,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22115417"],"URL":"https:\/\/doi.org\/10.3390\/ijms22115417","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,5,21]]}}}