{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T00:03:47Z","timestamp":1793577827428,"version":"4.5.0"},"reference-count":119,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Mol Neurobiol"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s12035-025-05492-2","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T08:39:59Z","timestamp":1767947999000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Metformin Improves Cognitive Function in a Rat Model of Global Cerebral Ischemia\/Reperfusion Injury Via Inhibiting NF-kb Signaling Pathway and Caspase-1\/NLRP3 Inflammasome"],"prefix":"10.1007","volume":"63","author":[{"given":"Zohreh","family":"Lamoochi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Esmaeil","family":"Khoshnam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam Khombi","family":"Shooshtari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Badavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaghoub","family":"Farbood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Sarkaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"issue":"10100","key":"5492_CR1","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/S0140-6736(17)32152-9","volume":"390","author":"J Christopher","year":"2017","unstructured":"Christopher J, Murray L (2017) Global, regional, and national age-sex specific mortality for 264 causes of death, 1980\u20132016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet (London, England) 390(10100):1151\u2013210","journal-title":"Lancet (London, England)"},{"issue":"5","key":"5492_CR2","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.bbadis.2016.01.015","volume":"1862","author":"RN Kalaria","year":"2016","unstructured":"Kalaria RN, Akinyemi R, Ihara M (2016) Stroke injury, cognitive impairment and vascular dementia. Biochimica et Biophysica Acta (BBA) 1862(5):915\u2013925. https:\/\/doi.org\/10.1016\/j.bbadis.2016.01.015","journal-title":"Biochimica et Biophysica Acta (BBA)"},{"key":"5492_CR3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0079-6123(08)61973-1","volume":"63","author":"WA Pulsinelli","year":"1985","unstructured":"Pulsinelli WA (1985) Selective neuronal vulnerability: morphological and molecular characteristics. Prog Brain Res 63:29\u201337","journal-title":"Prog Brain Res"},{"issue":"5","key":"5492_CR4","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1002\/ana.410110509","volume":"11","author":"WA Pulsinelli","year":"1982","unstructured":"Pulsinelli WA, Brierley JB, Plum F (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 11(5):491\u2013498","journal-title":"Ann Neurol"},{"key":"5492_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2022.109554","volume":"372","author":"ES Choi","year":"2022","unstructured":"Choi ES, Park GH, Kim DS, Shin HS, Park SY, Kim M, Hong JM (2022) A novel global ischemia-reperfusion rat model with asymmetric brain damage simulating post-cardiac arrest brain injury. J Neurosci Methods 372:109554. https:\/\/doi.org\/10.1016\/j.jneumeth.2022.109554","journal-title":"J Neurosci Methods"},{"issue":"2","key":"5492_CR6","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1111\/bpa.12476","volume":"27","author":"J Barrington","year":"2017","unstructured":"Barrington J, Lemarchand E, Allan SM (2017) A brain in flame; do inflammasomes and pyroptosis influence stroke pathology? Brain Pathol 27(2):205\u2013212. https:\/\/doi.org\/10.1111\/bpa.12476","journal-title":"Brain Pathol"},{"key":"5492_CR7","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.630536","volume":"12","author":"H Duez","year":"2021","unstructured":"Duez H, Pourcet B (2021) Nuclear receptors in the control of the NLRP3 inflammasome pathway. Front Endocrinol 12:630536. https:\/\/doi.org\/10.3389\/fendo.2021.630536","journal-title":"Front Endocrinol"},{"issue":"3","key":"5492_CR8","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.neubiorev.2008.10.005","volume":"33","author":"J McAfoose","year":"2009","unstructured":"McAfoose J, Baune BT (2009) Evidence for a cytokine model of cognitive function. Neurosci Biobehav Rev 33(3):355\u2013366","journal-title":"Neurosci Biobehav Rev"},{"issue":"8","key":"5492_CR9","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/s41581-020-0266-9","volume":"16","author":"D Viggiano","year":"2020","unstructured":"Viggiano D, Wagner CA, Martino G, Nedergaard M, Zoccali C, Unwin R, Capasso G (2020) Mechanisms of cognitive dysfunction in CKD. Nat Rev Nephrol 16(8):452\u2013469. https:\/\/doi.org\/10.1038\/s41581-020-0266-9","journal-title":"Nat Rev Nephrol"},{"issue":"6","key":"5492_CR10","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.clinph.2010.09.015","volume":"122","author":"AO Constantinescu","year":"2011","unstructured":"Constantinescu AO, Ilie A, Ciocan D, Zagrean AM, Zagrean L, Moldovan M (2011) Endogenous adenosine A1 receptor activation underlies the transient post-ischemic rhythmic delta EEG activity. Clin Neurophysiol 122(6):1117\u20131126. https:\/\/doi.org\/10.1016\/j.clinph.2010.09.015","journal-title":"Clin Neurophysiol"},{"issue":"3","key":"5492_CR11","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1097\/01.wnp.0000220094.60482.b5","volume":"23","author":"AM Husain","year":"2006","unstructured":"Husain AM (2006) Electroencephalographic assessment of coma. J Clin Neurophysiol 23(3):208\u2013220. https:\/\/doi.org\/10.1097\/01.wnp.0000220094.60482.b5","journal-title":"J Clin Neurophysiol"},{"issue":"1","key":"5492_CR12","first-page":"38","volume":"18","author":"M Dolatshahi","year":"2015","unstructured":"Dolatshahi M, Farbood Y, Sarkaki A, Mansouri SM, Khodadadi A (2015) Ellagic acid improves hyperalgesia and cognitive deficiency in 6-hydroxidopamine induced rat model of Parkinson\u2019s disease. Iran J Basic Med Sci 18(1):38\u201346","journal-title":"Iran J Basic Med Sci"},{"key":"5492_CR13","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/s12974-014-0177-4","volume":"11","author":"Y Liu","year":"2014","unstructured":"Liu Y, Tang G, Li Y, Wang Y, Chen X, Gu X et al (2014) Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion. J Neuroinflammation 11:177","journal-title":"J Neuroinflammation"},{"issue":"4","key":"5492_CR14","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1038\/ijo.2008.116","volume":"32","author":"DG Hardie","year":"2008","unstructured":"Hardie DG (2008) AMPK: a key regulator of energy balance in the single cell and the whole organism. International journal of obesity (2005) 32(4):S7-12","journal-title":"International journal of obesity (2005)"},{"issue":"3","key":"5492_CR15","doi-asserted-by":"publisher","first-page":"696","DOI":"10.2337\/db07-1098","volume":"57","author":"JW Calvert","year":"2008","unstructured":"Calvert JW, Gundewar S, Jha S, Greer JJ, Bestermann WH, Tian R et al (2008) Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling. Diabetes 57(3):696\u2013705","journal-title":"Diabetes"},{"issue":"3","key":"5492_CR16","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1007\/s11011-014-9632-2","volume":"30","author":"G Ashabi","year":"2015","unstructured":"Ashabi G, Khalaj L, Khodagholi F, Goudarzvand M, Sarkaki A (2015) Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia. Metab Brain Dis 30(3):747\u2013754","journal-title":"Metab Brain Dis"},{"key":"5492_CR17","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/s11011-013-9475-2","volume":"29","author":"G Ashabi","year":"2014","unstructured":"Ashabi G, Khodagholi F, Khalaj L, Goudarzvand M, Nasiri MJMbd (2014) Activation of AMP-activated protein kinase by metformin protects against global cerebral ischemia in male rats: interference of AMPK\/PGC-1\u03b1 pathway. Metab Brain Dis 29:47\u201358","journal-title":"Metab Brain Dis"},{"issue":"6","key":"5492_CR18","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.cell.2010.01.040","volume":"140","author":"K Schroder","year":"2010","unstructured":"Schroder K, Tschopp J (2010) The inflammasomes. Cell 140(6):821\u2013832","journal-title":"Cell"},{"issue":"3","key":"5492_CR19","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1161\/01.STR.10.3.267","volume":"10","author":"WA Pulsinelli","year":"1979","unstructured":"Pulsinelli WA, Brierley JB (1979) A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke 10(3):267\u2013272","journal-title":"Stroke"},{"key":"5492_CR20","volume-title":"The rat brain in stereotaxic coordinates (6e)","author":"G Paxinos","year":"2007","unstructured":"Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates (6e). Academic Press, New York"},{"key":"5492_CR21","doi-asserted-by":"crossref","unstructured":"Ferreira LO, Mattos BG, J\u00f3ia de Mello V, Martins-Filho AJ, Costa ETd, Yamada ES, et al (2021) Increased relative delta bandpower and delta indices revealed by continuous qEEG monitoring in a rat model of ischemia-reperfusion 12:645138.","DOI":"10.3389\/fneur.2021.645138"},{"key":"5492_CR22","doi-asserted-by":"crossref","unstructured":"Nejad KH, Sarkaki A, Dianat M, Farbood Y, Badavi M, Gharib-Naseri MKJBAoB, et al (2018) Preventive effects of ellagic acid on nucleus tractus solitarius electrical activity and oxidative stress altered by cerebral global ischemia\/reperfusion in rat 60.","DOI":"10.1590\/1678-4324-2017160264"},{"key":"5492_CR23","doi-asserted-by":"crossref","unstructured":"Zuo W, Zhang W, Han N, Chen NHJCN (2015) Therapeutics. compound imm\u2010h004, a novel coumarin derivative, protects against ca 1 cell loss and spatial learning impairments resulting from transient global ischemia 21(3):280\u20138.","DOI":"10.1111\/cns.12364"},{"issue":"5","key":"5492_CR24","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200121R","volume":"36","author":"M Shoaib","year":"2022","unstructured":"Shoaib M, Choudhary RC, Chillale RK, Kim N, Miyara SJ, Haque S, Yin T, Frankfurt M et al (2022) Metformin-mediated mitochondrial protection post-cardiac arrest improves EEG activity and confers neuroprotection and survival benefit. FASEB J 36(5):e22307. https:\/\/doi.org\/10.1096\/fj.202200121R","journal-title":"FASEB J"},{"issue":"4","key":"5492_CR25","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1161\/01.STR.26.4.627","volume":"26","author":"JH Garcia","year":"1995","unstructured":"Garcia JH, Wagner S, Liu K-F, Hu X-jJS (1995) Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats: statistical validation. Stroke 26(4):627\u2013635. https:\/\/doi.org\/10.1161\/01.STR.26.4.627","journal-title":"Stroke"},{"issue":"1","key":"5492_CR26","doi-asserted-by":"publisher","first-page":"23","DOI":"10.17219\/acem\/61044","volume":"26","author":"B Cevik","year":"2017","unstructured":"Cevik B, Solmaz V, Yigitturk G, Cavuso\u011flu T, Peker G, Erbas O (2017) Neuroprotective effects of erythropoietin on Alzheimer\u2019s dementia model in rats. Adv Clin Exp Med 26(1):23\u201329. https:\/\/doi.org\/10.17219\/acem\/61044","journal-title":"Adv Clin Exp Med"},{"issue":"6","key":"5492_CR27","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.4103\/1673-5374.300454","volume":"16","author":"HL Wang","year":"2021","unstructured":"Wang HL, Liu FL, Li RQ, Wan MY, Li JY, Shi J et al (2021) Electroacupuncture improves learning and memory functions in a rat cerebral ischemia\/reperfusion injury model through PI3K\/Akt signaling pathway activation. Neural Regen Res 16(6):1011\u20131016","journal-title":"Neural Regen Res"},{"issue":"3","key":"5492_CR28","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1007\/PL00005603","volume":"113","author":"A Ennaceur","year":"1997","unstructured":"Ennaceur A, Neave N, Aggleton JP (1997) Spontaneous object recognition and object location memory in rats: the effects of lesions in the cingulate cortices, the medial prefrontal cortex, the cingulum bundle and the fornix. Exp Brain Res 113(3):509\u2013519","journal-title":"Exp Brain Res"},{"issue":"2","key":"5492_CR29","first-page":"115","volume":"67","author":"G J\u00eetc\u0103","year":"2021","unstructured":"J\u00eetc\u0103 G, G\u00e1ll Z, Vari CE, \u0150sz BE, Tero-Vescan A, Gro\u0219an A et al (2021) Beneficial effects of metformin on haloperidol-induced motor deficits in rats. A behav assess 67(2):115\u201321","journal-title":"A behav assess"},{"key":"5492_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116797","volume":"175","author":"S Mohtadi","year":"2024","unstructured":"Mohtadi S, Salehcheh M, Tabandeh MR, Khorsandi L, Khodayar MJ (2024) Ketotifen counteracts cisplatin-induced acute kidney injury in mice via targeting NF-\u03baB\/NLRP3\/caspase-1 and Bax\/Bcl2\/caspase-3 signaling pathways. Biomed Pharmacother 175:116797. https:\/\/doi.org\/10.1016\/j.biopha.2024.116797","journal-title":"Biomed Pharmacother"},{"issue":"6","key":"5492_CR31","doi-asserted-by":"publisher","first-page":"677","DOI":"10.4103\/1735-5362.359434","volume":"17","author":"T Zamir-Nasta","year":"2022","unstructured":"Zamir-Nasta T, Abbasi A, Kakebaraie S, Ahmadi A, Pazhouhi M, Jalili C (2022) Aflatoxin G1 exposure altered the expression of BDNF and GFAP, histopathological of brain tissue, and oxidative stress factors in male rats. Research in Pharmaceutical Sciences 17(6):677\u201385","journal-title":"Research in Pharmaceutical Sciences"},{"key":"5492_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104261","volume":"146","author":"T Leech","year":"2019","unstructured":"Leech T, Chattipakorn N, Chattipakorn SC (2019) The beneficial roles of metformin on the brain with cerebral ischaemia\/reperfusion injury. Pharmacol Res 146:104261. https:\/\/doi.org\/10.1016\/j.phrs.2019.104261","journal-title":"Pharmacol Res"},{"issue":"2","key":"5492_CR33","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1093\/ilar.44.2.85","volume":"44","author":"RJ Traystman","year":"2003","unstructured":"Traystman RJ (2003) Animal models of focal and global cerebral ischemia. ILAR J 44(2):85\u201395","journal-title":"ILAR J"},{"issue":"2","key":"5492_CR34","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/j.1447-0594.2009.00571.x","volume":"10","author":"K Gustaw-Rothenberg","year":"2010","unstructured":"Gustaw-Rothenberg K, Kowalczuk K, Stryjecka-Zimmer M (2010) Lipids\u2019 peroxidation markers in Alzheimer\u2019s disease and vascular dementia. Geriatr Gerontol Int 10(2):161\u2013166","journal-title":"Geriatr Gerontol Int"},{"issue":"1","key":"5492_CR35","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/8624318","volume":"2022","author":"W Trujillo-Rangel","year":"2022","unstructured":"Trujillo-Rangel W, Garc\u00eda-Vald\u00e9s L, M\u00e9ndez-Del Villar M, Casta\u00f1eda-Arellano R, Totsuka-Sutto SE, Garc\u00eda-Benavides L (2022) Therapeutic targets for regulating oxidative damage induced by ischemia-reperfusion injury: a study from a pharmacological perspective. Oxid Med Cell Longev 2022(1):8624318. https:\/\/doi.org\/10.1155\/2022\/8624318","journal-title":"Oxid Med Cell Longev"},{"key":"5492_CR36","first-page":"1629","volume":"20","author":"JH Joo","year":"2014","unstructured":"Joo JH, Ryu D, Peng Q, Sugrue SP (2014) Role of Pnn in alternative splicing of a specific subset of lncRNAs of the corneal epithelium. Mol Vis 20:1629\u20131642","journal-title":"Mol Vis"},{"key":"5492_CR37","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11030466","author":"SY Hsu","year":"2022","unstructured":"Hsu SY, Chen CH, Mukda S, Leu S (2022) Neuronal Pnn deficiency increases oxidative stress and exacerbates cerebral ischemia\/reperfusion injury in mice. Antioxidants (Basel). https:\/\/doi.org\/10.3390\/antiox11030466","journal-title":"Antioxidants (Basel)"},{"key":"5492_CR38","doi-asserted-by":"publisher","first-page":"1394932","DOI":"10.3389\/fnmol.2024.1394932","volume":"17","author":"Y Lyu","year":"2024","unstructured":"Lyu Y, Meng Z, Hu Y, Jiang B, Yang J, Chen Y et al (2024) Mechanisms of mitophagy and oxidative stress in cerebral ischemia-reperfusion, vascular dementia, and Alzheimer\u2019s disease. Front Mol Neurosci 17:1394932","journal-title":"Front Mol Neurosci"},{"issue":"2","key":"5492_CR39","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s13311-018-0614-7","volume":"15","author":"AA Pradhan","year":"2018","unstructured":"Pradhan AA, Bertels Z, Akerman S (2018) Targeted nitric oxide synthase inhibitors for migraine. Neurotherapeutics 15(2):391\u2013401. https:\/\/doi.org\/10.1007\/s13311-018-0614-7","journal-title":"Neurotherapeutics"},{"issue":"4","key":"5492_CR40","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1159\/000489241","volume":"46","author":"MY Wu","year":"2018","unstructured":"Wu MY, Yliang GT, Liao WT, Tsai AP, Cheng YL, Cheng PW et al (2018) Current mechanistic concepts in ischemia and reperfusion injury. Cell Physiol Biochem 46(4):1650\u20131667","journal-title":"Cell Physiol Biochem"},{"issue":"2","key":"5492_CR41","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1097\/00002093-199100520-00007","volume":"5","author":"H Naritomi","year":"1991","unstructured":"Naritomi H (1991) Experimental basis of multi-infarct dementia: memory impairments in rodent models of ischemia. Alzheimer Dis Assoc Disord 5(2):103\u2013111","journal-title":"Alzheimer Dis Assoc Disord"},{"issue":"1","key":"5492_CR42","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.jneumeth.2007.06.032","volume":"166","author":"JM Silvers","year":"2007","unstructured":"Silvers JM, Harrod SB, Mactutus CF, Booze RM (2007) Automation of the novel object recognition task for use in adolescent rats. J Neurosci Methods 166(1):99\u2013103","journal-title":"J Neurosci Methods"},{"issue":"4","key":"5492_CR43","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/j.neuroscience.2010.03.032","volume":"167","author":"BK Goulart","year":"2010","unstructured":"Goulart BK, de Lima MN, de Farias CB, Reolon GK, Almeida VR, Quevedo J et al (2010) Ketamine impairs recognition memory consolidation and prevents learning-induced increase in hippocampal brain-derived neurotrophic factor levels. Neuroscience 167(4):969\u2013973","journal-title":"Neuroscience"},{"issue":"2","key":"5492_CR44","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s10339-011-0430-z","volume":"13","author":"M Antunes","year":"2012","unstructured":"Antunes M, Biala G (2012) The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process 13(2):93\u2013110","journal-title":"Cogn Process"},{"key":"5492_CR45","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-015-0027-6","volume":"10","author":"G O\u2019Neal-Moffitt","year":"2015","unstructured":"O\u2019Neal-Moffitt G, Delic V, Bradshaw PC, Olcese J (2015) Prophylactic melatonin significantly reduces Alzheimer\u2019s neuropathology and associated cognitive deficits independent of antioxidant pathways in A\u03b2PP(swe)\/PS1 mice. Mol Neurodegener 10:27","journal-title":"Mol Neurodegener"},{"issue":"1","key":"5492_CR46","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3233\/JAD-141332","volume":"44","author":"KA DiTacchio","year":"2015","unstructured":"DiTacchio KA, Heinemann SF, Dziewczapolski G (2015) Metformin treatment alters memory function in a mouse model of Alzheimer\u2019s disease. J Alzheimers Dis 44(1):43\u201348. https:\/\/doi.org\/10.3233\/JAD-141332","journal-title":"J Alzheimers Dis"},{"issue":"1","key":"5492_CR47","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S0166-4328(05)80036-1","volume":"42","author":"LA Rothblat","year":"1991","unstructured":"Rothblat LA, Kromer LF (1991) Object recognition memory in the rat: the role of the hippocampus. Behav Brain Res 42(1):25\u201332","journal-title":"Behav Brain Res"},{"key":"5492_CR48","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.832611","volume":"13","author":"K Liu","year":"2022","unstructured":"Liu K, Li L, Liu Z, Li G, Wu Y, Jiang X, Wang M, Chang Y, et al. (2022) Acute administration of metformin protects against neuronal apoptosis induced by cerebral ischemia-reperfusion injury via regulation of the AMPK\/CREB\/BDNF pathway. Front Pharmacol 13:832611. https:\/\/doi.org\/10.3389\/fphar.2022.832611","journal-title":"Front Pharmacol"},{"issue":"1","key":"5492_CR49","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s11011-011-9235-0","volume":"26","author":"L-X Li","year":"2011","unstructured":"Li L-X, Cheng Y-F, Lin H-B, Wang C, Xu J-P, Zhang H-T (2011) Prevention of cerebral ischemia-induced memory deficits by inhibition of phosphodiesterase-4 in rats. Metab Brain Dis 26(1):37\u201347","journal-title":"Metab Brain Dis"},{"key":"5492_CR50","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.physbeh.2016.12.021","volume":"170","author":"X-H Ge","year":"2017","unstructured":"Ge X-H, Zhu G-J, Geng D-Q, Zhang H-Z, He J-M, Guo A-Z et al (2017) Metformin protects the brain against ischemia\/reperfusion injury through PI3K\/Akt1\/JNK3 signaling pathways in rats. Physiol Behav 170:115\u2013123","journal-title":"Physiol Behav"},{"issue":"1","key":"5492_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-021-00683-8","volume":"22","author":"Z Qin","year":"2021","unstructured":"Qin Z, Zhou C, Xiao X, Guo CJBn (2021) Metformin attenuates sepsis-induced neuronal injury and cognitive impairment. BMC Neurosci 22(1):78. https:\/\/doi.org\/10.1186\/s12868-021-00683-8","journal-title":"BMC Neurosci"},{"key":"5492_CR52","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00170","author":"Y Wang","year":"2020","unstructured":"Wang Y, Zhao J, Guo F-L, Gao X, Xie X, Liu S et al (2020) Metformin ameliorates synaptic defects in a mouse model of AD by inhibiting Cdk5 activity. Front Cell Neurosci. https:\/\/doi.org\/10.3389\/fncel.2020.00170","journal-title":"Front Cell Neurosci"},{"key":"5492_CR53","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2021.113343","volume":"410","author":"EAC Gorgich","year":"2021","unstructured":"Gorgich EAC, Parsaie H, Yarmand S, Baharvand F, Sarbishegi M (2021) Long-term administration of metformin ameliorates age-dependent oxidative stress and cognitive function in rats. Behav Brain Res 410:113343. https:\/\/doi.org\/10.1016\/j.bbr.2021.113343","journal-title":"Behav Brain Res"},{"issue":"1","key":"5492_CR54","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s40168-023-01567-1","volume":"11","author":"X Zhu","year":"2023","unstructured":"Zhu X, Shen J, Feng S, Huang C, Wang H, Huo F et al (2023) Akkermansia muciniphila, which is enriched in the gut microbiota by metformin, improves cognitive function in aged mice by reducing the proinflammatory cytokine interleukin-6. Microbiome 11(1):120","journal-title":"Microbiome"},{"issue":"2","key":"5492_CR55","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/S0165-0173(98)00056-3","volume":"29","author":"W Klimesch","year":"1999","unstructured":"Klimesch W (1999) EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain Res Rev 29(2):169\u2013195. https:\/\/doi.org\/10.1016\/S0165-0173(98)00056-3","journal-title":"Brain Res Rev"},{"issue":"8","key":"5492_CR56","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1016\/j.clinph.2004.03.009","volume":"115","author":"SP Fitzgibbon","year":"2004","unstructured":"Fitzgibbon SP, Pope KJ, Mackenzie L, Clark CR, Willoughby JO (2004) Cognitive tasks augment gamma EEG power. Clin Neurophysiol 115(8):1802\u20131809","journal-title":"Clin Neurophysiol"},{"issue":"10","key":"5492_CR57","doi-asserted-by":"publisher","first-page":"25605","DOI":"10.3390\/ijms161025605","volume":"16","author":"G Rabiller","year":"2015","unstructured":"Rabiller G, He JW, Nishijima Y, Wong A, Liu J (2015) Perturbation of brain oscillations after ischemic stroke: a potential biomarker for post-stroke function and therapy. Int J Mol Sci 16(10):25605\u201325640","journal-title":"Int J Mol Sci"},{"key":"5492_CR58","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.brainresbull.2014.01.003","volume":"102","author":"SG Moyanova","year":"2014","unstructured":"Moyanova SG, Dijkhuizen RM (2014) Present status and future challenges of electroencephalography- and magnetic resonance imaging-based monitoring in preclinical models of focal cerebral ischemia. Brain Res Bull 102:22\u201336","journal-title":"Brain Res Bull"},{"issue":"3","key":"5492_CR59","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/0306-4522(89)90423-5","volume":"31","author":"G Buzs\u00e1ki","year":"1989","unstructured":"Buzs\u00e1ki G (1989) Two-stage model of memory trace formation: a role for \u201cnoisy\u201d brain states. Neuroscience 31(3):551\u2013570","journal-title":"Neuroscience"},{"key":"5492_CR60","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.brainres.2014.10.034","volume":"1621","author":"J Larson","year":"2015","unstructured":"Larson J, Munk\u00e1csy E (2015) Theta-burst LTP. Brain Res 1621:38\u201350","journal-title":"Brain Res"},{"issue":"10","key":"5492_CR61","doi-asserted-by":"publisher","first-page":"3788","DOI":"10.1093\/cercor\/bhu263","volume":"25","author":"R Honkanen","year":"2015","unstructured":"Honkanen R, Rouhinen S, Wang SH, Palva JM, Palva S (2015) Gamma oscillations underlie the maintenance of feature-specific information and the contents of visual working memory. Cereb Cortex 25(10):3788\u2013801","journal-title":"Cereb Cortex"},{"issue":"1","key":"5492_CR62","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s10548-014-0361-y","volume":"28","author":"U Maurer","year":"2015","unstructured":"Maurer U, Brem S, Liechti M, Maurizio S, Michels L, Brandeis D (2015) Frontal midline theta reflects individual task performance in a working memory task. Brain Topogr 28(1):127\u2013134","journal-title":"Brain Topogr"},{"issue":"7","key":"5492_CR63","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/j.neubiorev.2009.12.014","volume":"34","author":"E Nyhus","year":"2010","unstructured":"Nyhus E, Curran T (2010) Functional role of gamma and theta oscillations in episodic memory. Neurosci Biobehav Rev 34(7):1023\u20131035","journal-title":"Neurosci Biobehav Rev"},{"issue":"5","key":"5492_CR64","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/S1474-4422(13)70060-7","volume":"12","author":"JM Wardlaw","year":"2013","unstructured":"Wardlaw JM, Smith C, Dichgans M (2013) Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 12(5):483\u2013497","journal-title":"Lancet Neurol"},{"issue":"3","key":"5492_CR65","doi-asserted-by":"publisher","first-page":"124","DOI":"10.5812\/atr.10240","volume":"2","author":"MA Atlasi","year":"2013","unstructured":"Atlasi MA, Naderian H, Noureddini M, Fakharian E, Azami A (2013) Morphology of rat hippocampal CA1 neurons following modified two and four-vessels global ischemia models. Arch Trauma Res 2(3):124\u2013128","journal-title":"Arch Trauma Res"},{"issue":"5","key":"5492_CR66","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1523\/JNEUROSCI.4105-07.2008","volume":"28","author":"C Huchzermeyer","year":"2008","unstructured":"Huchzermeyer C, Albus K, Gabriel HJ, Ot\u00e1hal J, Taubenberger N, Heinemann U, Kov\u00e1cs R, Kann O (2008) Gamma oscillations and spontaneous network activity in the hippocampus are highly sensitive to decreases in pO2 and concomitant changes in mitochondrial redox state. J Neurosci 28(5):1153\u20131162. https:\/\/doi.org\/10.1523\/JNEUROSCI.4105-07.2008","journal-title":"J Neurosci"},{"issue":"6","key":"5492_CR67","doi-asserted-by":"publisher","first-page":"884","DOI":"10.3171\/jns.1993.78.6.0884","volume":"78","author":"LA Kearse Jr","year":"1993","unstructured":"Kearse LA Jr, Martin D, McPeck K, Lopez-Bresnahan M (1993) Computer-derived density spectral array in detection of mild analog electroencephalographic ischemic pattern changes during carotid endarterectomy. J Neurosurg 78(6):884\u2013890","journal-title":"J Neurosurg"},{"issue":"9","key":"5492_CR68","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1089\/neu.2010.1370","volume":"27","author":"M Fedor","year":"2010","unstructured":"Fedor M, Berman RF, Muizelaar JP, Lyeth BG (2010) Hippocampal \u03b8 dysfunction after lateral fluid percussion injury. J Neurotrauma 27(9):1605\u20131615","journal-title":"J Neurotrauma"},{"issue":"2","key":"5492_CR69","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1046\/j.1460-9568.2003.02444.x","volume":"17","author":"D Van Dam","year":"2003","unstructured":"Van Dam D, D\u2019Hooge R, Staufenbiel M, Van Ginneken C, Van Meir F, De Deyn PP (2003) Age-dependent cognitive decline in the APP23 model precedes amyloid deposition. Eur J Neurosci 17(2):388\u2013396","journal-title":"Eur J Neurosci"},{"issue":"2","key":"5492_CR70","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/S0197-4580(02)00098-2","volume":"24","author":"PH Kelly","year":"2003","unstructured":"Kelly PH, Bondolfi L, Hunziker D, Schlecht HP, Carver K, Maguire E et al (2003) Progressive age-related impairment of cognitive behavior in APP23 transgenic mice. Neurobiol Aging 24(2):365\u2013378","journal-title":"Neurobiol Aging"},{"key":"5492_CR71","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40478-014-0149-z","volume":"2","author":"AA Ittner","year":"2014","unstructured":"Ittner AA, Gladbach A, Bertz J, Suh LS, Ittner LM (2014) P38 MAP kinase-mediated NMDA receptor-dependent suppression of hippocampal hypersynchronicity in a mouse model of Alzheimer\u2019s disease. Acta Neuropathol Commun 2:1\u201317","journal-title":"Acta Neuropathol Commun"},{"key":"5492_CR72","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.bbi.2020.06.001","volume":"89","author":"M-h Ji","year":"2020","unstructured":"Ji M-h, Lei L, Gao D-p, Tong J-h, Wang Y, Yang J-jJB (2020) Neural network disturbance in the medial prefrontal cortex might contribute to cognitive impairments induced by neuroinflammation. Brain Behav Immun 89:133\u2013144","journal-title":"Brain Behav Immun"},{"issue":"12","key":"5492_CR73","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.2174\/1567205017666191213162233","volume":"16","author":"F Pe\u00f1a-Ortega","year":"2019","unstructured":"Pe\u00f1a-Ortega F (2019) Brain arrhythmias induced by amyloid beta and inflammation: involvement in Alzheimer\u2019s disease and other inflammation-related pathologies. Curr Alzheimer Res 16(12):1108\u20131131","journal-title":"Curr Alzheimer Res"},{"issue":"2","key":"5492_CR74","doi-asserted-by":"publisher","first-page":"349","DOI":"10.3233\/JAD-2009-1059","volume":"17","author":"DV Moretti","year":"2009","unstructured":"Moretti DV, Pievani M, Fracassi C, Binetti G, Rosini S, Geroldi C, Zanetti O, Rossini PM et al (2009) Increase of theta\/gamma and alpha3\/alpha2 ratio is associated with amygdalo-hippocampal complex atrophy. J Alzheimers Dis 17(2):349\u2013357. https:\/\/doi.org\/10.3233\/JAD-2009-1059","journal-title":"J Alzheimers Dis"},{"key":"5492_CR75","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1111\/j.1749-6632.2010.05761.x","volume":"1207","author":"GJ del Zoppo","year":"2010","unstructured":"del Zoppo GJ (2010) Acute anti-inflammatory approaches to ischemic stroke. Ann N Y Acad Sci 1207:143\u2013148","journal-title":"Ann N Y Acad Sci"},{"key":"5492_CR76","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/j.1749-6632.2010.05735.x","volume":"1207","author":"OA Harari","year":"2010","unstructured":"Harari OA, Liao JK (2010) NF-\u03baB and innate immunity in ischemic stroke. Ann N Y Acad Sci 1207:32\u201340","journal-title":"Ann N Y Acad Sci"},{"issue":"3","key":"5492_CR77","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1172\/JCI65167","volume":"123","author":"N Deroide","year":"2013","unstructured":"Deroide N, Li X, Lerouet D, Van Vr\u00e9 E, Baker L, Harrison J et al (2013) MFGE8 inhibits inflammasome-induced IL-1\u03b2 production and limits postischemic cerebral injury. J Clin Invest 123(3):1176\u20131181","journal-title":"J Clin Invest"},{"issue":"7","key":"5492_CR78","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/nri3705","volume":"14","author":"MT Heneka","year":"2014","unstructured":"Heneka MT, Kummer MP, Latz E (2014) Innate immune activation in neurodegenerative disease. Nat Rev Immunol 14(7):463\u2013477","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"5492_CR79","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/s12035-014-8866-7","volume":"52","author":"XC Zhu","year":"2015","unstructured":"Zhu XC, Jiang T, Zhang QQ, Cao L, Tan MS, Wang HF et al (2015) Chronic metformin preconditioning provides neuroprotection via suppression of NF-\u03baB-mediated inflammatory pathway in rats with permanent cerebral ischemia. Mol Neurobiol 52(1):375\u2013385","journal-title":"Mol Neurobiol"},{"issue":"5","key":"5492_CR80","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1038\/8432","volume":"5","author":"A Schneider","year":"1999","unstructured":"Schneider A, Martin-Villalba A, Weih F, Vogel J, Wirth T, Schwaninger M (1999) NF-kappaB is activated and promotes cell death in focal cerebral ischemia. Nat Med 5(5):554\u2013559","journal-title":"Nat Med"},{"issue":"4","key":"5492_CR81","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/j.arr.2013.09.004","volume":"12","author":"DY Fann","year":"2013","unstructured":"Fann DY, Lee SY, Manzanero S, Chunduri P, Sobey CG, Arumugam TV (2013) Pathogenesis of acute stroke and the role of inflammasomes. Ageing Res Rev 12(4):941\u2013966. https:\/\/doi.org\/10.1016\/j.arr.2013.09.004","journal-title":"Ageing Res Rev"},{"issue":"6","key":"5492_CR82","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1177\/1747493019841242","volume":"14","author":"M Alishahi","year":"2019","unstructured":"Alishahi M, Farzaneh M, Ghaedrahmati F, Nejabatdoust A, Sarkaki A, Khoshnam SE (2019) NLRP3 inflammasome in ischemic stroke: as possible therapeutic target. Int J Stroke 14(6):574\u2013591. https:\/\/doi.org\/10.1177\/1747493019841242","journal-title":"Int J Stroke"},{"issue":"1","key":"5492_CR83","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/S0006-291X(02)02573-1","volume":"299","author":"L Xu","year":"2002","unstructured":"Xu L, Zhan Y, Wang Y, Feuerstein GZ, Wang X (2002) Recombinant adenoviral expression of dominant negative IkappaBalpha protects brain from cerebral ischemic injury. Biochem Biophys Res Commun 299(1):14\u201317","journal-title":"Biochem Biophys Res Commun"},{"key":"5492_CR84","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174146","volume":"903","author":"TF Docrat","year":"2021","unstructured":"Docrat TF, Nagiah S, Chuturgoon AA (2021) Metformin protects against neuroinflammation through integrated mechanisms of miR-141 and the NF-\u0138B-mediated inflammasome pathway in a diabetic mouse model. Eur J Pharmacol 903:174146. https:\/\/doi.org\/10.1016\/j.ejphar.2021.174146","journal-title":"Eur J Pharmacol"},{"key":"5492_CR85","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.brainres.2016.05.013","volume":"1644","author":"WH Oliveira","year":"2016","unstructured":"Oliveira WH, Nunes AK, Fran\u00e7a MER, Santos LA, L\u00f3s DB, Rocha SW et al (2016) Effects of metformin on inflammation and short-term memory in streptozotocin-induced diabetic mice. Brain Res 1644:149\u2013160","journal-title":"Brain Res"},{"key":"5492_CR86","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117861","volume":"255","author":"PM Saffari","year":"2020","unstructured":"Saffari PM, Alijanpour S, Takzaree N, Sahebgharani M, Etemad-Moghadam S, Noorbakhsh F, Partoazar A (2020) Metformin loaded phosphatidylserine nanoliposomes improve memory deficit and reduce neuroinflammation in streptozotocin-induced Alzheimer\u2019s disease model. Life Sci 255:117861. https:\/\/doi.org\/10.1016\/j.lfs.2020.117861","journal-title":"Life Sci"},{"key":"5492_CR87","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.801337","volume":"13","author":"Y Zhang","year":"2022","unstructured":"Zhang Y, Zhang H, Li S, Huang K, Jiang L, Wang Y (2022) Metformin alleviates LPS-induced acute lung injury by regulating the SIRT1\/NF-\u03baB\/NLRP3 pathway and inhibiting endothelial cell pyroptosis. Front Pharmacol 13:801337. https:\/\/doi.org\/10.3389\/fphar.2022.801337","journal-title":"Front Pharmacol"},{"issue":"6","key":"5492_CR88","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.cmet.2014.09.018","volume":"20","author":"M Foretz","year":"2014","unstructured":"Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B (2014) Metformin: from mechanisms of action to therapies. Cell Metab 20(6):953\u2013966","journal-title":"Cell Metab"},{"key":"5492_CR89","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/2049-3002-2-12","volume":"2","author":"S Andrzejewski","year":"2014","unstructured":"Andrzejewski S, Gravel SP, Pollak M, St-Pierre J (2014) Metformin directly acts on mitochondria to alter cellular bioenergetics. Cancer Metab 2:12","journal-title":"Cancer Metab"},{"key":"5492_CR90","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.bbr.2019.01.048","volume":"363","author":"M Zhao","year":"2019","unstructured":"Zhao M, Cheng X, Lin X, Han Y, Zhou Y, Zhao T et al (2019) Metformin administration prevents memory impairment induced by hypobaric hypoxia in rats. Behav Brain Res 363:30\u201337","journal-title":"Behav Brain Res"},{"issue":"10","key":"5492_CR91","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.3109\/13880209.2016.1150306","volume":"54","author":"N Ghadernezhad","year":"2016","unstructured":"Ghadernezhad N, Khalaj L, Pazoki-Toroudi H, Mirmasoumi M, Ashabi G (2016) Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK\/BDNF\/P70SK signalling pathway. Pharm Biol 54(10):2211\u20132219","journal-title":"Pharm Biol"},{"issue":"1","key":"5492_CR92","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.stem.2012.03.016","volume":"11","author":"J Wang","year":"2012","unstructured":"Wang J, Gallagher D, DeVito LM, Cancino GI, Tsui D, He L et al (2012) Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. Cell Stem Cell 11(1):23\u201335","journal-title":"Cell Stem Cell"},{"issue":"1","key":"5492_CR93","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1111\/jnc.13726","volume":"139","author":"JL Hill","year":"2016","unstructured":"Hill JL, Kobori N, Zhao J, Rozas NS, Hylin MJ, Moore AN et al (2016) Traumatic brain injury decreases AMP-activated protein kinase activity and pharmacological enhancement of its activity improves cognitive outcome. J Neurochem 139(1):106\u2013119","journal-title":"J Neurochem"},{"issue":"11\u201312","key":"5492_CR94","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.lfs.2012.08.017","volume":"91","author":"H Pintana","year":"2012","unstructured":"Pintana H, Apaijai N, Pratchayasakul W, Chattipakorn N, Chattipakorn SC (2012) Effects of metformin on learning and memory behaviors and brain mitochondrial functions in high fat diet induced insulin resistant rats. Life Sci 91(11\u201312):409\u2013414. https:\/\/doi.org\/10.1016\/j.lfs.2012.08.017","journal-title":"Life Sci"},{"issue":"2","key":"5492_CR95","doi-asserted-by":"publisher","first-page":"186","DOI":"10.2174\/1570159X11666131120223201","volume":"12","author":"KH Alzoubi","year":"2014","unstructured":"Alzoubi KH, Khabour OF, Al-Azzam SI, Tashtoush MH, Mhaidat NM (2014) Metformin eased cognitive impairment induced by chronic l-methionine administration: potential role of oxidative stress. Curr Neuropharmacol 12(2):186\u2013192","journal-title":"Curr Neuropharmacol"},{"issue":"4","key":"5492_CR96","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.bbrc.2014.04.130","volume":"448","author":"RR Zhao","year":"2014","unstructured":"Zhao RR, Xu XC, Xu F, Zhang WL, Zhang WL, Liu LM, Wang W-P (2014) Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice. Biochem Biophys Res Commun 448(4):414\u2013417. https:\/\/doi.org\/10.1016\/j.bbrc.2014.04.130","journal-title":"Biochem Biophys Res Commun"},{"key":"5492_CR97","doi-asserted-by":"publisher","DOI":"10.3390\/ph14090890","author":"SR Poor","year":"2021","unstructured":"Poor SR, Ettcheto M, Cano A, Sanchez-Lopez E, Manzine PR, Olloquequi J et al (2021) Metformin a potential pharmacological strategy in late onset Alzheimer\u2019s disease treatment. Pharmaceuticals (Basel, Switzerland). https:\/\/doi.org\/10.3390\/ph14090890","journal-title":"Pharmaceuticals (Basel, Switzerland)"},{"issue":"42","key":"5492_CR98","doi-asserted-by":"publisher","first-page":"21848","DOI":"10.1074\/jbc.C116.732990","volume":"291","author":"K Tikoo","year":"2016","unstructured":"Tikoo K, Sharma E, Amara VR, Pamulapati H, Dhawale VS (2016) Metformin improves metabolic memory in high fat diet (HFD)-induced renal dysfunction. J Biol Chem 291(42):21848\u201321856","journal-title":"J Biol Chem"},{"key":"5492_CR99","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2021.117520","volume":"287","author":"P Su","year":"2021","unstructured":"Su P, Wang D, Cao Z, Chen J, Zhang J (2021) The role of NLRP3 in lead-induced neuroinflammation and possible underlying mechanism. Environ Pollut 287:117520","journal-title":"Environ Pollut"},{"key":"5492_CR100","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2021.126919","volume":"71","author":"B Ben-Azu","year":"2022","unstructured":"Ben-Azu B, Adebayo OG, Wopara I, Aduema W, Onyeleonu I, Umoren EB, Kolawole TA, Ebo OT, et al. (2022) Lead acetate induces hippocampal pyramidal neuron degeneration in mice via up-regulation of executioner caspase-3, oxido-inflammatory stress expression and decreased BDNF and cholinergic activity: reversal effects of Gingko biloba supplement. J Trace Elem Med Biol 71:126919. https:\/\/doi.org\/10.1016\/j.jtemb.2021.126919","journal-title":"J Trace Elem Med Biol"},{"key":"5492_CR101","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121895","volume":"328","author":"AA Ibrahim","year":"2023","unstructured":"Ibrahim AA, Abdel Mageed SS, Safar MM, El-Yamany MF, Oraby MA (2023) MitoQ alleviates hippocampal damage after cerebral ischemia: the potential role of SIRT6 in regulating mitochondrial dysfunction and neuroinflammation. Life Sci 328:121895. https:\/\/doi.org\/10.1016\/j.lfs.2023.121895","journal-title":"Life Sci"},{"key":"5492_CR102","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.bbi.2020.06.001","volume":"89","author":"M-h Ji","year":"2020","unstructured":"Ji M-h, Lei L, Gao D-p, Tong J-h, Wang Y, Yang J-j (2020) Neural network disturbance in the medial prefrontal cortex might contribute to cognitive impairments induced by neuroinflammation. Brain Behav Immun 89:133\u2013144","journal-title":"Brain Behav Immun"},{"issue":"1","key":"5492_CR103","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1186\/s12974-016-0754-9","volume":"13","author":"Y Pan","year":"2016","unstructured":"Pan Y, Sun X, Jiang L, Hu L, Kong H, Han Y et al (2016) Metformin reduces morphine tolerance by inhibiting microglial-mediated neuroinflammation. J Neuroinflammation 13(1):294","journal-title":"J Neuroinflammation"},{"issue":"6","key":"5492_CR104","doi-asserted-by":"publisher","first-page":"410.e1","DOI":"10.1016\/j.jpurol.2016.06.017","volume":"12","author":"A Asghari","year":"2016","unstructured":"Asghari A, Akbari G, Meghdadi A, Mortazavi P (2016) Effects of melatonin and metformin co-administration on testicular ischemia\/reperfusion injury in rats. J Pediatr Urol 12(6):410.e1-e7","journal-title":"J Pediatr Urol"},{"issue":"23","key":"5492_CR105","doi-asserted-by":"publisher","first-page":"24270","DOI":"10.18632\/aging.202143","volume":"12","author":"J Zhang","year":"2020","unstructured":"Zhang J, Huang L, Shi X, Yang L, Hua F, Ma J et al (2020) Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK\/NLRP3 inflammasome pathway. Aging 12(23):24270\u201324287","journal-title":"Aging"},{"issue":"3","key":"5492_CR106","doi-asserted-by":"publisher","first-page":"389","DOI":"10.2174\/1570159X13666150205143555","volume":"13","author":"J Jia","year":"2015","unstructured":"Jia J, Cheng J, Ni J, Zhen X (2015) Neuropharmacological actions of metformin in stroke. Curr Neuropharmacol 13(3):389\u2013394","journal-title":"Curr Neuropharmacol"},{"key":"5492_CR107","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/746068","volume":"2013","author":"RA Taylor","year":"2013","unstructured":"Taylor RA, Sansing LH (2013) Microglial responses after ischemic stroke and intracerebral hemorrhage. Clin Dev Immunol 2013:746068","journal-title":"Clin Dev Immunol"},{"issue":"6","key":"5492_CR108","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1007\/s11064-021-03270-9","volume":"46","author":"T Zhang","year":"2021","unstructured":"Zhang T, He MT, Zhang XP, Jing L, Zhang JZ (2021) Uncoupling protein 2 deficiency enhances NLRP3 inflammasome activation following hyperglycemia-induced exacerbation of cerebral ischemia and reperfusion damage in vitro and in vivo. Neurochem Res 46(6):1359\u20131371","journal-title":"Neurochem Res"},{"issue":"10","key":"5492_CR109","doi-asserted-by":"publisher","first-page":"2912","DOI":"10.1007\/s11064-017-2322-9","volume":"42","author":"B Qi","year":"2017","unstructured":"Qi B, Hu L, Zhu L, Shang L, Wang X, Liu N et al (2017) Metformin attenuates neurological deficit after intracerebral hemorrhage by inhibiting apoptosis, oxidative stress and neuroinflammation in rats. Neurochem Res 42(10):2912\u20132920","journal-title":"Neurochem Res"},{"issue":"12","key":"5492_CR110","doi-asserted-by":"publisher","DOI":"10.3390\/ph16121714","volume":"16","author":"LM Isop","year":"2023","unstructured":"Isop LM, Neculau AE, Necula RD, Kakucs C, Moga MA, Dima LJP (2023) Metformin: the winding path from understanding its molecular mechanisms to proving therapeutic benefits in neurodegenerative disorders. Pharmaceuticals 16(12):1714","journal-title":"Pharmaceuticals"},{"issue":"1","key":"5492_CR111","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1139\/cjpp-2018-0266","volume":"97","author":"AM Hussein","year":"2019","unstructured":"Hussein AM, Eldosoky M, El-Shafey M, El-Mesery M, Ali AN, Abbas KM, Abulseoud OA (2019) Effects of metformin on apoptosis and \u03b1-synuclein in a rat model of pentylenetetrazole-induced epilepsy. Can J Physiol Pharmacol 97(1):37\u201346. https:\/\/doi.org\/10.1139\/cjpp-2018-0266","journal-title":"Can J Physiol Pharmacol"},{"issue":"7","key":"5492_CR112","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.2337\/db14-1683","volume":"64","author":"Y Wu","year":"2015","unstructured":"Wu Y, Wang F, Fu M, Wang C, Quon MJ, Yang P (2015) Cellular stress, excessive apoptosis, and the effect of metformin in a mouse model of type 2 diabetic embryopathy. Diabetes 64(7):2526\u20132536","journal-title":"Diabetes"},{"issue":"7","key":"5492_CR113","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e17873","volume":"9","author":"S Rabieipoor","year":"2023","unstructured":"Rabieipoor S, Zare M, Ettcheto M, Camins A, Javan M (2023) Metformin restores cognitive dysfunction and histopathological deficits in an animal model of sporadic Alzheimer\u2019s disease. Heliyon 9(7):e17873. https:\/\/doi.org\/10.1016\/j.heliyon.2023.e17873","journal-title":"Heliyon"},{"issue":"1","key":"5492_CR114","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.jsps.2019.11.013","volume":"28","author":"RF Abdel-Rahman","year":"2020","unstructured":"Abdel-Rahman RF, Alqasoumi SI, Ogaly HA, Abd-Elsalam RM, El-Banna HA, Soliman GA (2020) Propolis ameliorates cerebral injury in focal cerebral ischemia\/reperfusion (I\/R) rat model via upregulation of TGF-\u03b21. Saudi Pharm J 28(1):116\u2013126. https:\/\/doi.org\/10.1016\/j.jsps.2019.11.013","journal-title":"Saudi Pharm J"},{"issue":"10","key":"5492_CR115","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165893","volume":"1866","author":"J Benjanuwattra","year":"2020","unstructured":"Benjanuwattra J, Apaijai N, Chunchai T, Kerdphoo S, Jaiwongkam T, Arunsak B et al (2020) Metformin preferentially provides neuroprotection following cardiac ischemia\/reperfusion in non-diabetic rats. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1866(10):165893","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"},{"key":"5492_CR116","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2020.00028","volume":"13","author":"L Wu","year":"2020","unstructured":"Wu L, Xiong X, Wu X, Ye Y, Jian Z, Zhi Z, Gu L (2020) Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury. Front Mol Neurosci 13:28. https:\/\/doi.org\/10.3389\/fnmol.2020.00028","journal-title":"Front Mol Neurosci"},{"key":"5492_CR117","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2021.109090","volume":"352","author":"W Sun","year":"2021","unstructured":"Sun W, Chen Y, Zhang Y, Geng Y, Tang X, Guo R, Zhang Z, Xu H et al (2021) A modified four vessel occlusion model of global cerebral ischemia in rats. J Neurosci Methods 352:109090. https:\/\/doi.org\/10.1016\/j.jneumeth.2021.109090","journal-title":"J Neurosci Methods"},{"key":"5492_CR118","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.brainresbull.2022.03.008","volume":"183","author":"Z Yang","year":"2022","unstructured":"Yang Z, Li X, Cao Z, Wang P, Warner DS, Sheng H (2022) Post-ischemia common carotid artery occlusion worsens memory loss, but not sensorimotor deficits, in long-term survived stroke mice. Brain Res Bull 183:153\u2013161","journal-title":"Brain Res Bull"},{"issue":"1","key":"5492_CR119","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01688-x","volume":"9","author":"M Zhang","year":"2024","unstructured":"Zhang M, Liu Q, Meng H, Duan H, Liu X, Wu J et al (2024) Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets. Signal Transduct Target Ther 9(1):12","journal-title":"Signal Transduct Target Ther"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-05492-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-025-05492-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-05492-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T21:02:54Z","timestamp":1767992574000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-025-05492-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":119,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["5492"],"URL":"https:\/\/doi.org\/10.1007\/s12035-025-05492-2","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"15 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experimental protocols were performed according to the Local Ethics Committee of the Ahvaz Jundishapur University of Medical Sciences (AJUMS), Iran (Ethic code: IR.AJUMS.ABHC.REC.1402.003).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"353"}}