{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T18:07:10Z","timestamp":1776362830296,"version":"3.51.2"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1007\/s00210-025-04872-8","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T07:35:33Z","timestamp":1765006533000},"page":"7243-7260","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clonidine attenuates chronic hypoxic stress-induced behavioral abnormalities in male Swiss mice through suppression of oxidative stress and pro-inflammatory cytokines"],"prefix":"10.1007","volume":"399","author":[{"given":"Demilade Timothy","family":"Adebayo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4150-8331","authenticated-orcid":false,"given":"Clinton","family":"Ijirigho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8466-2807","authenticated-orcid":false,"given":"Paul Ademola","family":"Adeleke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanel Soremekun","family":"Oladimeji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9614-2748","authenticated-orcid":false,"given":"Favour Boluwatife","family":"Jegede","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0351-3629","authenticated-orcid":false,"given":"Gbemisayo Adetomiwa","family":"Abbas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8837-4557","authenticated-orcid":false,"given":"Lily Oghenevovwero","family":"Otomewo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6586-0421","authenticated-orcid":false,"given":"Abayomi Mayowa","family":"Ajayi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2065-5111","authenticated-orcid":false,"given":"Solomon","family":"Umukoro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"4872_CR1","volume":"12","author":"AG Abbas","year":"2024","unstructured":"Abbas AG, Ajiboye OB, Adeleke PA, Ajayi AM, Okubena O, Umukoro S (2024) Polyphenol-rich Sorghum bicolor supplement exhibits anti-nociceptive activity and protective effects against pathological changes associated with complete Freund\u2019s adjuvant induced arthritis in rodents. Pharmacol Res 12:100481","journal-title":"Pharmacol Res"},{"issue":"3","key":"4872_CR2","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1080\/19390211.2021.2025008","volume":"20","author":"EN Abd Al Haleem","year":"2023","unstructured":"Abd Al Haleem EN, Ahmed HI, El-Naga RN (2023) Lycopene and chrysin through mitigation of neuroinflammation and oxidative stress exerted antidepressant effects in clonidine-induced depression-like behavior in rats. J Diet Suppl 20(3):391\u2013410. https:\/\/doi.org\/10.1080\/19390211.2021.2025008","journal-title":"J Diet Suppl"},{"key":"4872_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.prmcm.2025.100665","volume":"16","author":"VA Adeoye","year":"2025","unstructured":"Adeoye VA, Ajayi AM, Orodeh PO, Chimezie J, Enebeli L, Adeleke PA, Owoeye O, Umukoro S (2025) Aqueous extract of Hibiscus sabdariffa calyces offers neuroprotection against unpredictable chronic mild stress-induced neurobehavioral disorders and biochemical perturbations in male Swiss mice. Pharmacol Res-Mod Chin Med 16:100665. https:\/\/doi.org\/10.1016\/j.prmcm.2025.100665","journal-title":"Pharmacol Res-Mod Chin Med"},{"issue":"1","key":"4872_CR4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.17712\/nsj.2025.1.20240052","volume":"30","author":"EA Albadawi","year":"2025","unstructured":"Albadawi EA (2025) Structural and functional changes in the hippocampus induced by environmental exposures. Neurosciences 30(1):5\u201319. https:\/\/doi.org\/10.17712\/nsj.2025.1.20240052","journal-title":"Neurosciences"},{"key":"4872_CR5","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1007\/s10735-025-10532-1","volume":"56","author":"OS Annafi","year":"2025","unstructured":"Annafi OS, Adeleke PA, Enebeli L, Ajayi AM, Okubena O, Umukoro S (2025) Sorghum bicolor supplement attenuates rotenone-induced behavioral derangements in rats through neuroprotective mechanisms and modulation of tyrosine hydroxylase and \u03b1-synuclein\/NF-kB immunopositive cells expressions. J Mol Histol 56:254. https:\/\/doi.org\/10.1007\/s10735-025-10532-1","journal-title":"J Mol Histol"},{"key":"4872_CR6","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1017\/S2045796011000096","volume":"20","author":"M Bellani","year":"2011","unstructured":"Bellani M, Baiano M, Brambilla P (2011) Brain anatomy of major depression II. Focus on amygdala. Epidemiol Psychiatr Sci 20:33\u201336","journal-title":"Epidemiol Psychiatr Sci"},{"issue":"5","key":"4872_CR7","first-page":"262","volume":"7","author":"K Blum","year":"2024","unstructured":"Blum K (2024) The impact of chronic stress on brain function and structure. Neurosci Psych Open Access 7(5):262\u2013264","journal-title":"Neurosci Psych Open Access"},{"key":"4872_CR8","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1111\/1523-1747.ep12506462","volume":"78","author":"PP Bradley","year":"1982","unstructured":"Bradley PP, Priebat DA, Christensen RD, Rothstein G (1982) Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206\u2013209. https:\/\/doi.org\/10.1111\/1523-1747.ep12506462","journal-title":"J Invest Dermatol"},{"key":"4872_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104718","volume":"138","author":"M Burtscher","year":"2022","unstructured":"Burtscher M, Gatterer H, Millet GP (2022) The interplay of hypoxic and mental stress: implications for anxiety and depressive disorders. Neurosci Biobehav Rev 138:104718. https:\/\/doi.org\/10.1016\/j.neubiorev.2022.104718","journal-title":"Neurosci Biobehav Rev"},{"key":"4872_CR10","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3233\/NRE-2010-0531","volume":"26","author":"KM Busl","year":"2010","unstructured":"Busl KM, Greer DM (2010) Hypoxic-ischemic brain injury: pathophysiology, neuropathology and mechanisms. Neurorehabil 26:5\u201313","journal-title":"Neurorehabil"},{"key":"4872_CR11","doi-asserted-by":"crossref","unstructured":"Cervo L, Samanin R (1991) Clonidine causes antidepressant-like effects in rats by activating \u03b12-adrenoceptors outside the locus coeruleus. Eur J Pharmacol 193(3):309\u2013313","DOI":"10.1016\/0014-2999(91)90144-F"},{"issue":"6","key":"4872_CR12","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1007\/s11011-022-01028-y","volume":"37","author":"J Chen","year":"2022","unstructured":"Chen J, Zhang J, Yang DD, Li ZC, Zhao B, Chen Y, He Z (2022) Clonidine ameliorates cerebral ischemia\u2013reperfusion injury by up-regulating the GluN3 subunits of NMDA receptor. Metab Brain Dis 37(6):1829\u20131841. https:\/\/doi.org\/10.1007\/s11011-022-01028-y","journal-title":"Metab Brain Dis"},{"key":"4872_CR13","doi-asserted-by":"publisher","first-page":"421","DOI":"10.3389\/fimmu.2020.00421","volume":"11","author":"YM Chen","year":"2020","unstructured":"Chen YM, He XZ, Wang SM, Xia Y (2020) \u03b4-opioid receptors, microRNAs, and neuroinflammation in cerebral ischemia\/hypoxia. Front Immunol 11:421. https:\/\/doi.org\/10.3389\/fimmu.2020.00421","journal-title":"Front Immunol"},{"key":"4872_CR14","unstructured":"Chiu S, Campbell K (2018) Clonidine for the treatment of psychiatric conditions and symptoms: a review of clinical effectiveness, safety, and guidelines. [Internet]. Canadian Agency for Drugs and Technologies in Health,  Ottawa. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK531717\/"},{"key":"4872_CR15","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/s12031-015-0547-0","volume":"56","author":"Y Chtourou","year":"2015","unstructured":"Chtourou Y, Gargouri B, Kebieche M, Fetoui H (2015) Naringin abrogates cisplatin-induced cognitive deficits and cholinergic dysfunction through the down-regulation of AChE expression and iNOS signaling pathways in hippocampus of aged rats. J Mol Neurosci 56:349\u2013362. https:\/\/doi.org\/10.1007\/s12031-015-0547-0","journal-title":"J Mol Neurosci"},{"key":"4872_CR16","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.4049\/jimmunol.165.2.1013","volume":"165","author":"NS Chandel","year":"2000","unstructured":"Chandel NS, Trzyna WC, McClintock DS, Schumacker PT (2000) Role of oxidants in NF-kappa B activation and TNF-alpha gene transcription induced by hypoxia and endotoxin. J Immunol 165:1013\u20131021. https:\/\/doi.org\/10.4049\/jimmunol.165.2.1013","journal-title":"J Immunol"},{"key":"4872_CR17","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2020.552969","volume":"11","author":"J Dumanovi\u0107","year":"2020","unstructured":"Dumanovi\u0107 J, Nepovimova E, Nati\u0107 M, Ku\u010da K, Ja\u0107evi\u0107 V (2020) The significance of reactive oxygen species and antioxidant defense system in plants: a concise overview. Front Plant Sci 11:552969. https:\/\/doi.org\/10.3389\/fpls.2020.552969","journal-title":"Front Plant Sci"},{"key":"4872_CR18","doi-asserted-by":"publisher","first-page":"176","DOI":"10.3389\/fpsyt.2020.00176","volume":"11","author":"G Dossi","year":"2020","unstructured":"Dossi G, Delvecchio G, Prunas C, Soares JC, Brambilla P (2020) Neural bases of cognitive impairments in post-traumatic stress disorders: a mini-review of functional magnetic resonance imaging findings. Front Psychiatry 11:176. https:\/\/doi.org\/10.3389\/fpsyt.2020.00176","journal-title":"Front Psychiatry"},{"key":"4872_CR19","doi-asserted-by":"publisher","first-page":"3239","DOI":"10.1007\/s11064-016-2050-6","volume":"41","author":"AT Eduviere","year":"2016","unstructured":"Eduviere AT, Umukoro S, Adeoluwa OA, Omogbiya IA, Aluko OM (2016) Possible mechanisms involved in attenuation of lipopolysaccharide-induced memory deficits by methyl jasmonate in mice. Neurochem Res 41:3239\u20133249","journal-title":"Neurochem Res"},{"issue":"1","key":"4872_CR20","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03118-3","volume":"21","author":"MG El Baassiri","year":"2024","unstructured":"El Baassiri MG, Raouf Z, Badin S, Escobosa A, Sodhi CP, Nasr IW (2024) Dysregulated brain\u2013gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies. J Neuroinflammation 21(1):124. https:\/\/doi.org\/10.1186\/s12974-024-03118-3","journal-title":"J Neuroinflammation"},{"issue":"2","key":"4872_CR21","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","volume":"7","author":"GL Ellman","year":"1961","unstructured":"Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7(2):88\u201395. https:\/\/doi.org\/10.1016\/0006-2952(61)90145-9","journal-title":"Biochem Pharmacol"},{"issue":"8","key":"4872_CR22","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1093\/jpp\/rgac039","volume":"74","author":"MH Fawzy","year":"2022","unstructured":"Fawzy MH, Khodeer DM, Elsayed NM, Ahmed YM, Saeed NM (2022) Clonidine ameliorates cisplatin-induced nephrotoxicity: impact on OCT2 and p38 MAPK pathway. J Pharm Pharmacol 74(8):1180\u20131192. https:\/\/doi.org\/10.1093\/jpp\/rgac039","journal-title":"J Pharm Pharmacol"},{"key":"4872_CR23","doi-asserted-by":"publisher","first-page":"3238","DOI":"10.1007\/s12035-021-02362-9","volume":"58","author":"Y Fan","year":"2021","unstructured":"Fan Y, Chou MC, Liu YC, Liu CK, Chen CH, Chen SL (2021) Intermittent hypoxia activates N-methyl-D-aspartate receptors to induce anxiety behaviors in a mouse model of sleep-associated apnea. Mol Neurobiol 58:3238\u20133251. https:\/\/doi.org\/10.1007\/s12035-021-02362-9","journal-title":"Mol Neurobiol"},{"key":"4872_CR24","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S0006-8993(09)90005-1","volume":"658","author":"S Feldman","year":"1994","unstructured":"Feldman S, Conforti N, Itzik A, Weidenfeld J (1994) Differential effect of amygdaloid lesions on CRF-41, ACTH and corticosterone responses following neural stimuli. Brain Res 658:21\u201326","journal-title":"Brain Res"},{"key":"4872_CR25","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s00044-015-1495-5","volume":"25","author":"M Gaba","year":"2016","unstructured":"Gaba M, Mohan C (2016) Development of drugs based on imidazole and benzimidazole bioactive heterocycles: recent advances and future directions. Med Chem Res 25:173\u2013210. https:\/\/doi.org\/10.1007\/s00044-015-1495-5","journal-title":"Med Chem Res"},{"issue":"1","key":"4872_CR26","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/0003-2697(82)90118-X","volume":"126","author":"LC Green","year":"1982","unstructured":"Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126(1):131\u2013138","journal-title":"Anal Biochem"},{"key":"4872_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2024.100670","volume":"33","author":"M Girotti","year":"2024","unstructured":"Girotti M, Bulin SE, Carreno FR (2024) Effects of chronic stress on cognitive function - from neurobiology to intervention. Neurobiol Stress 33:100670. https:\/\/doi.org\/10.1016\/j.ynstr.2024.100670","journal-title":"Neurobiol Stress"},{"issue":"2\u20133","key":"4872_CR28","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/0009-8981(91)90067-M","volume":"196","author":"L Goth","year":"1991","unstructured":"Goth L (1991) A simple method for determination of serum catalase activity and revision of reference range. Clinica Chimica Acta 196(2\u20133):143\u2013151","journal-title":"Clinica Chimica Acta"},{"key":"4872_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116428","volume":"174","author":"Y He","year":"2024","unstructured":"He Y, He T, Li H, Chen W, Zhong B, Wu Y, Han Z (2024) Deciphering mitochondrial dysfunction: pathophysiological mechanisms in vascular cognitive impairment. Biomed Pharmacother 174:116428","journal-title":"Biomed Pharmacother"},{"issue":"5","key":"4872_CR30","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1007\/s11011-024-01354-3","volume":"39","author":"Z He","year":"2024","unstructured":"He Z, Yin BK, Wang K, Zhao B, Chen Y, Li ZC, Chen J (2024b) The alpha2-adrenergic receptor agonist clonidine protects against cerebral ischemia\/reperfusion induced neuronal apoptosis in rats. Metab Brain Dis 39(5):741\u2013752","journal-title":"Metab Brain Dis"},{"key":"4872_CR31","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1017\/S0033291713001529","volume":"44","author":"UK Haukvik","year":"2014","unstructured":"Haukvik UK, McNeil T, Lange EH, Melle I, Dale AM, Andreassen OA, Agartz I (2014) Pre- and perinatal hypoxia associated with hippocampus\/amygdala volume in bipolar disorder. Psychol Med 44:975\u2013985","journal-title":"Psychol Med"},{"key":"4872_CR32","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/S0166-2236(96)10069-2","volume":"20","author":"JP Herman","year":"1997","unstructured":"Herman JP, Cullinan WE (1997) Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis. Trends Neurosci 20:78\u201384","journal-title":"Trends Neurosci"},{"key":"4872_CR33","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1213\/00000539-199110000-00016","volume":"73","author":"WE Hoffman","year":"1991","unstructured":"Hoffman WE, Cheng MA, Thomas C, Baughman VL, Albrecht RF (1991) Clonidine decreases plasma catecholamines and improves outcome from incomplete ischemia in the rat. Anesth Analg 73:460\u2013464. https:\/\/doi.org\/10.1213\/00000539-199110000-00016","journal-title":"Anesth Analg"},{"issue":"3","key":"4872_CR34","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1159\/000136485","volume":"11","author":"DJ Jollow","year":"1974","unstructured":"Jollow DJ, Mitchell JR, Zampaglione NA, Gillette JR (1974) Bromobenzene-induced liver necrosis, protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacol 11(3):151\u2013169","journal-title":"Pharmacol"},{"issue":"7","key":"4872_CR35","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1177\/0271678X17719375","volume":"38","author":"A Klass","year":"2018","unstructured":"Klass A, S\u00e1nchez-Porras R, Santos E (2018) Systematic review of the pharmacological agents that have been tested against spreading depolarizations. J Cereb Blood Flow Metab 38(7):1149\u20131179. https:\/\/doi.org\/10.1177\/0271678X17719375","journal-title":"J Cereb Blood Flow Metab"},{"key":"4872_CR36","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1097\/00000542-200011000-00030","volume":"93","author":"T Kamibayashi","year":"2000","unstructured":"Kamibayashi T, Maze M (2000) Clinical uses of alpha2-adrenergic agonists. Anesthesiology 93:1345\u20131349. https:\/\/doi.org\/10.1097\/00000542-200011000-00030","journal-title":"Anesthesiology"},{"key":"4872_CR37","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0006-8993(91)91397-S","volume":"568","author":"Y Kamisaki","year":"1991","unstructured":"Kamisaki Y, Hamahashi T, Okada CM, Itoh T (1991) Clonidine inhibition of potassium-evoked release of glutamate and aspartate from rat cortical synaptosomes. Brain Res 568:193\u2013198. https:\/\/doi.org\/10.1016\/0006-8993(91)91397-S","journal-title":"Brain Res"},{"issue":"1","key":"4872_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01109-9","volume":"7","author":"Z Luo","year":"2022","unstructured":"Luo Z, Tian M, Yang G, Tan Q, Chen Y, Li G, Zhang Q, Li Y, Wan P, Wu J (2022) Hypoxia signaling in human health and diseases: implications and prospects for therapeutics. Signal Transduct Target Ther 7(1):218. https:\/\/doi.org\/10.1038\/s41392-022-01109-9","journal-title":"Signal Transduct Target Ther"},{"key":"4872_CR39","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","volume":"193","author":"OH Lowry","year":"1951","unstructured":"Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265\u2013275","journal-title":"J Biol Chem"},{"key":"4872_CR40","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1097\/00000542-200201000-00026","volume":"96","author":"V Laudenbach","year":"2002","unstructured":"Laudenbach V, Mantz J, Lagercrantz H, Desmonts JM, Evrard P, Gressens P (2002) Effects of alpha(2)-adrenoceptor agonists on perinatal excitotoxic brain injury: comparison of clonidine and dexmedetomidine. Anesthesiology 96:134\u2013141. https:\/\/doi.org\/10.1097\/00000542-200201000-00026","journal-title":"Anesthesiology"},{"issue":"10","key":"4872_CR41","doi-asserted-by":"publisher","first-page":"3170","DOI":"10.1016\/S0021-9258(19)45228-9","volume":"247","author":"HP Misra","year":"1972","unstructured":"Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247(10):3170\u20133175","journal-title":"J Biol Chem"},{"key":"4872_CR42","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/nri.2015.5","volume":"16","author":"AH Miller","year":"2016","unstructured":"Miller AH, Raison CL (2016) The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol 16:22. https:\/\/doi.org\/10.1038\/nri.2015.5","journal-title":"Nat Rev Immunol"},{"key":"4872_CR43","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/j.1749-6632.2009.05331.x","volume":"1186","author":"BS McEwen","year":"2010","unstructured":"McEwen BS, Gianaros PJ (2010) Central role of the brain in stress and adaptation: links to socioeconomic status, health, and disease. Ann N Y Acad Sci 1186:190\u2013222","journal-title":"Ann N Y Acad Sci"},{"issue":"1","key":"4872_CR44","doi-asserted-by":"publisher","DOI":"10.1080\/20008198.2024.2366049","volume":"15","author":"M Marchi","year":"2024","unstructured":"Marchi M, Grenzi P, Boks MP (2024) Clonidine for post-traumatic stress disorder: a systematic review of the current evidence. Eur J Psychotraumatol 15(1):2366049. https:\/\/doi.org\/10.1080\/20008198.2024.2366049","journal-title":"Eur J Psychotraumatol"},{"key":"4872_CR45","doi-asserted-by":"publisher","unstructured":"Nguyen KT, Gates CA, Hassell JE Jr, Foxx CL, Salazar SN, Luthens AK, Arnold AL, Elam BL, Elsayed AI, Leblanc M, Adams SC, Lowry CA, Reuter JD (2021) Evaluation of the effects of altitude on biological signatures of inflammation and anxiety- and depressive-like behavioral responses. Prog Neuropsychopharmacol Biol Psychiatry 111:110331. https:\/\/doi.org\/10.1016\/j.pnpbp.2021.110331","DOI":"10.1016\/j.pnpbp.2021.110331"},{"key":"4872_CR46","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.brainresbull.2020.12.003","volume":"169","author":"S Olugbemide","year":"2021","unstructured":"Olugbemide S, Ben-Azu B, Bakre AG, Ajayi AM, Femi-Akinlosotu O, Umukoro S (2021) Naringenin improves depressive- and anxiety-like behaviors in mice exposed to repeated hypoxic stress through modulation of oxido-inflammatory mediators and NF-kB\/BDNF expressions. Brain Res Bull 169:214\u2013227. https:\/\/doi.org\/10.1016\/j.brainresbull.2020.12.003","journal-title":"Brain Res Bull"},{"key":"4872_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.prmcm.2025.100578","volume":"14","author":"JO Oni","year":"2025","unstructured":"Oni JO, Oyenekan DO, Olayemi YO, Irabor OC, Ogbuji P, Tova MO, Adeleke PA, Abbas GA, Umukoro S (2025) Ginseng exhibits adaptogenic-like activity in mice exposed to hypoxic-anoxic stress via multiple mechanisms relating to activation of antioxidant\/BDNF protective mechanisms and inhibition of pro-inflammatory cytokines\/NF-kB signaling pathways. Pharmacol Res Mod Chin Med 14:100578. https:\/\/doi.org\/10.1016\/j.prmcm.2025.100578","journal-title":"Pharmacol Res Mod Chin Med"},{"key":"4872_CR48","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8978704","author":"X Peng","year":"2020","unstructured":"Peng X, Li C, Yu W, Liu S, Cong Y, Fan G, Qi S (2020) Propofol attenuates hypoxia-induced inflammation in BV2 microglia by inhibiting oxidative stress and NF-\u03baB\/Hif-1\u03b1 signaling. Biomed Res Int. https:\/\/doi.org\/10.1155\/2020\/8978704","journal-title":"Biomed Res Int"},{"issue":"1","key":"4872_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/stresses3010001","volume":"3","author":"A Recchia","year":"2022","unstructured":"Recchia A, Tonti MP, Mirabella L, Izzi A, Del Gaudio A (2022) The pharmacological class alpha 2 agonists for stress control in patients with respiratory failure: the main actor in the different acts. Stresses 3(1):1\u201310. https:\/\/doi.org\/10.3390\/stresses3010001","journal-title":"Stresses"},{"key":"4872_CR50","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1037\/0033-295X.105.2.325","volume":"105","author":"JB Rosen","year":"1998","unstructured":"Rosen JB, Schulkin J (1998) From normal fear to pathological anxiety. Psychol Rev 105:325\u2013350","journal-title":"Psychol Rev"},{"issue":"1","key":"4872_CR51","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1017\/S1092852918001426","volume":"24","author":"T Ramey","year":"2019","unstructured":"Ramey T, Regier PS (2019) Cognitive impairment in substance use disorders. CNS Spectr 24(1):102\u2013113. https:\/\/doi.org\/10.1017\/S1092852918001426","journal-title":"CNS Spectr"},{"key":"4872_CR52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/alzrt7","volume":"1","author":"SD Rountree","year":"2009","unstructured":"Rountree SD, Chan W, Pavlik VN, Darby EJ, Siddiqui S, Doody RS (2009) Persistent treatment with cholinesterase inhibitors and\/or memantine slows clinical progression of Alzheimer disease. Alzheimers Res Ther 1:1\u20137. https:\/\/doi.org\/10.1186\/alzrt7","journal-title":"Alzheimers Res Ther"},{"key":"4872_CR53","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/BF00428203","volume":"85","author":"L Steru","year":"1985","unstructured":"Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367\u2013370","journal-title":"Psychopharmacology"},{"issue":"1","key":"4872_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53624-1","volume":"9","author":"A Sequeira-Cordero","year":"2019","unstructured":"Sequeira-Cordero A, Salas-Bastos A, Fornaguera J, Brenes JC (2019) Behavioural characterization of chronic unpredictable stress based on ethologically relevant paradigms in rats. Sci Rep 9(1):17403. https:\/\/doi.org\/10.1038\/s41598-019-53624-1","journal-title":"Sci Rep"},{"issue":"3","key":"4872_CR55","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26031251","volume":"26","author":"OM Shirokova","year":"2025","unstructured":"Shirokova OM, Kuzmina DM, Zaborskaya OG, Shchelchkova NA, Kozliaeva EV, Korotchenko SA, Pershin VI, Vasilchikov PI, Mukhina IV (2025) The long-term effects of chronic unpredictable mild stress experienced during adolescence could vary depending on biological sex. Int J Mol Sci 26(3):1251. https:\/\/doi.org\/10.3390\/ijms26031251","journal-title":"Int J Mol Sci"},{"key":"4872_CR56","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1037\/a0035302","volume":"140","author":"GM Slavich","year":"2014","unstructured":"Slavich GM, Irwin MR (2014) From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol Bull 140:774\u2013815. https:\/\/doi.org\/10.1037\/a0035302","journal-title":"Psychol Bull"},{"key":"4872_CR57","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081584","volume":"8","author":"SM Smith","year":"2013","unstructured":"Smith SM, Friedle SA, Watters JJ (2013) Chronic intermittent hypoxia exerts CNS region-specific effects on rat microglial inflammatory and TLR4 gene expression. PLoS One 8:e81584. https:\/\/doi.org\/10.1371\/journal.pone.0081584","journal-title":"PLoS One"},{"issue":"6","key":"4872_CR58","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1134\/S0022093022060291","volume":"58","author":"DG Semenov","year":"2022","unstructured":"Semenov DG, Belyakov AV, Rybnikova EA (2022) Experimental modeling of damaging and protective hypoxia of the mammalian brain. J Evol Biochem Physiol 58(6):2021\u20132034. https:\/\/doi.org\/10.1134\/S0022093022060291","journal-title":"J Evol Biochem Physiol"},{"issue":"12","key":"4872_CR59","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3263","volume":"9","author":"Q Tang","year":"2019","unstructured":"Tang Q, Su YW, Xian CJ (2019) Determining oxidative damage by lipid peroxidation assay in rat serum. Bio-protocol 9(12):e3263","journal-title":"Bio-protocol"},{"key":"4872_CR60","doi-asserted-by":"publisher","first-page":"15959","DOI":"10.3390\/ijms140815959","volume":"14","author":"X Tian","year":"2013","unstructured":"Tian X, Hua F, Sandhu HK, Chao D, Balboni G, Salvadori S, He X, Xia Y (2013) Effect of \u03b4-opioid receptor activation on BDNF-TrkB vs. TNF-\u03b1 in the mouse cortex exposed to prolonged hypoxia. Int J Mol Sci 14:15959\u201315976","journal-title":"Int J Mol Sci"},{"issue":"2","key":"4872_CR61","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s10557-024-07574-0","volume":"24","author":"MA Werida","year":"2024","unstructured":"Werida MA, El-Sayed MM, El-Sayed MM (2024) Chemotherapy-induced cardiotoxicity: mechanisms and potential protective strategies. Cardiovasc Toxicol 24(2):123\u2013145. https:\/\/doi.org\/10.1007\/s10557-024-07574-0","journal-title":"Cardiovasc Toxicol"},{"key":"4872_CR62","doi-asserted-by":"publisher","DOI":"10.1177\/24705470211029254","author":"E Woo","year":"2021","unstructured":"Woo E, Sansing LH, Arnsten AFT, Datta D (2021) Chronic stress weakens connectivity in the prefrontal cortex: architectural and molecular changes. Chron Stress. https:\/\/doi.org\/10.1177\/24705470211029254","journal-title":"Chron Stress"},{"key":"4872_CR63","doi-asserted-by":"publisher","first-page":"125","DOI":"10.3922\/j.psns.2014.02.03","volume":"7","author":"K Yamada","year":"2014","unstructured":"Yamada K, Satake S, Perry J, Garcia K, D\u2019Almeida V, Tufik S, Longo B, da Silva BR (2014) Effect of postnatal intermittent hypoxia on locomotor activity and neuronal development of rats tested in early adulthood. Psychol Neurosci 7:125\u2013130. https:\/\/doi.org\/10.3922\/j.psns.2014.02.03","journal-title":"Psychol Neurosci"},{"key":"4872_CR64","first-page":"4232","volume":"27","author":"K-D Zeng","year":"2023","unstructured":"Zeng K-D, Wang G-l, Yuan Y, Zhang W, Huang X-H, Hu b (2023) Efficacy of clonidine in the treatment of children with tic disorder co-morbid with attention deficit hyperactivity disorder. Eur Rev Med Pharmacol Sci 27:4232\u20134238","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"4872_CR65","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.neuropharm.2013.03.020","volume":"74","author":"Q Zhou","year":"2013","unstructured":"Zhou Q, Sheng M (2013) NMDA receptors in nervous system diseases. Neuropharmacology 74:69\u201375. https:\/\/doi.org\/10.1016\/j.neuropharm.2013.03.020","journal-title":"Neuropharmacology"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04872-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-025-04872-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04872-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T17:02:03Z","timestamp":1776358923000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-025-04872-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,6]]},"references-count":65,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["4872"],"URL":"https:\/\/doi.org\/10.1007\/s00210-025-04872-8","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,6]]},"assertion":[{"value":"23 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The University of Ibadan Animal Care and Use Research Ethics Committee approved the experimental procedures (NHREC\/ACUREC\/05\/12\/2022A).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors approved the submission of the manuscript and consent to its publication in this journal.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}