{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T19:55:35Z","timestamp":1785354935422,"version":"3.55.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Minufiya University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Spinal cord ischemia reperfusion injury (IRI) occurs with an incidence of 1\u201332%, often leading to paraplegia with limited prevention options. Pridopidine (Prdpn), a highly selective sigma-1 receptor (Sig-1R) agonist, serves as a protein chaperone that is engaged in neuroplasticity and cellular defense. This research aimed to assess the neuroprotective properties of Prdpn in spinal cord IRI in rats and investigate the underlying mechanisms. Forty male Wistar albino rats were randomly allocated into 4 groups: control, sham, IRI, and IRI + Prdpn. Tarlov\u2019s test was used to examine behavioral performance, as well as withdrawal from agonizing stimuli and the placing\/stepping reflex (SPR). Biochemical markers, including spinal malondialdehyde (MDA), AOPP, antioxidant GPX, TNF-\u03b1 and IL-1\u03b2, and apoptotic caspase-3, were measured, along with BDNF, GDNF, and Sig-1R gene expression. Histopathological changes in spinal cord tissue were also evaluated. Spinal cord IRI significantly caused neurological deficits, evidenced by lower scores in Tarlov\u2019s test, withdrawal from agonizing stimuli, and SPR. Biochemically, spinal cord IRI led to decreased GPX and increased MDA, AOPP, TNF-\u03b1, IL-1\u03b2, caspase-3, and GDNF levels, along with downregulated BDNF and Sig-1R gene expression. Histopathologically, spinal cord IRI resulted in greater spinal neuronal degeneration, apoptosis, and demyelination. However, treatment with Prdpn significantly improved behavioral outcomes and partially reversed the biochemical and histopathological alterations. Prdpn improved spinal cord IRI-induced behavioral deficits through its antioxidant, anti-inflammatory, anti-apoptotic, and neurotrophic properties. It suggests promise as a potential treatment option to stop spinal cord IRI.<\/jats:p>","DOI":"10.1007\/s00210-025-03851-3","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T08:09:38Z","timestamp":1739347778000},"page":"9307-9321","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting the sigma-1 receptor with pridopidine induces functional neurorestoration in spinal cord ischemia-reperfusion injury"],"prefix":"10.1007","volume":"398","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3689-2648","authenticated-orcid":false,"given":"Eman","family":"Sweed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2535-9445","authenticated-orcid":false,"given":"Suzan A.","family":"Khodir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1977-6541","authenticated-orcid":false,"given":"Shaimaa Mohamed","family":"Motawea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9938-3907","authenticated-orcid":false,"given":"Hala","family":"El-Haron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4513-9427","authenticated-orcid":false,"given":"Basma Abdelnaby","family":"Mostafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4128-5632","authenticated-orcid":false,"given":"Mona S.","family":"Elkholy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammud","family":"Salim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7070-0844","authenticated-orcid":false,"given":"Doaa Z. M.","family":"Shebl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"3851_CR1","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1080\/08923973.2024.2390463","volume":"46","author":"HI Abd-Elhafiz","year":"2024","unstructured":"Abd-Elhafiz HI, Faried MA, Khodir SA, Moaty AS, Sweed EM (2024) Ezetimibe protects against gentamycin-induced ototoxicity in rats by antioxidants, anti-inflammatory mechanisms, and BDNF upregulation. Immunopharmacol Immunotoxicol 46:635\u2013650","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"3851_CR2","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3390\/diseases10020030","volume":"10","author":"S Aghili-Mehrizi","year":"2022","unstructured":"Aghili-Mehrizi S, Williams E, Yan S, Willman M, Willman J, Lucke-Wold B (2022) Secondary mechanisms of neurotrauma: a closer look at the evidence. Diseases 10:30","journal-title":"Diseases"},{"key":"3851_CR3","doi-asserted-by":"publisher","first-page":"7533","DOI":"10.3390\/ijms21207533","volume":"21","author":"A Anjum","year":"2020","unstructured":"Anjum A, Yazid MDI, Fauzi Daud M, Idris J, Ng AMH, Selvi Naicker A, Ismail OHR, Athi Kumar RK, Lokanathan Y (2020) Spinal cord injury: pathophysiology, multimolecular interactions, and underlying recovery mechanisms. Int J Mol Sci 21:7533","journal-title":"Int J Mol Sci"},{"key":"3851_CR4","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1002\/ar.23728","volume":"301","author":"J Bahney","year":"2018","unstructured":"Bahney J, von Bartheld CS (2018) The cellular composition and glia\u2013neuron ratio in the spinal cord of a human and a nonhuman primate: comparison with other species and brain regions. Anatomic Record 301:697\u2013710","journal-title":"Anatomic Record"},{"key":"3851_CR5","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1080\/10790268.2019.1600829","volume":"43","author":"SO Bashir","year":"2020","unstructured":"Bashir SO, Morsy MD, El Agamy DF (2020) Two episodes of remote ischemia preconditioning improve motor and sensory function of hind limbs after spinal cord ischemic injury. J Spinal Cord Med 43:878\u2013887","journal-title":"J Spinal Cord Med"},{"key":"3851_CR6","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1080\/14728222.2020.1805435","volume":"24","author":"JM Brimson","year":"2020","unstructured":"Brimson JM, Brimson S, Chomchoei C, Tencomnao T (2020) Using sigma-ligands as part of a multi-receptor approach to target diseases of the brain. Expert Opin Ther Targets 24:1009\u20131028","journal-title":"Expert Opin Ther Targets"},{"key":"3851_CR7","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1089\/neu.2022.0499","volume":"40","author":"D Chow","year":"2023","unstructured":"Chow D, Nguyen A, Park J, Wu L, Toups E, Harrop J, Guest J, Schmitt K, Aarabi B, Fehlings M (2023) The RISCIS-PK substudy: an analysis of pharmacokinetics, pharmacodynamics, and impact on axonal degradation of riluzole in patients with traumatic cervical spinal cord injury enrolled in the RISCIS Phase III Randomized Controlled Trial. J Neurotr 40:1889\u20131906","journal-title":"J Neurotr"},{"key":"3851_CR8","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/s10571-020-00983-3","volume":"42","author":"S Couly","year":"2022","unstructured":"Couly S, Goguadze N, Yasui Y, Kimura Y, Wang SM, Sharikadze N, Wu HE, Su TP (2022) Knocking out sigma-1 receptors reveals diverse health problems. Cell Mol Neurobiol 42:597\u2013620","journal-title":"Cell Mol Neurobiol"},{"key":"3851_CR9","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/00008506-200101000-00002","volume":"13","author":"P de Haan","year":"2001","unstructured":"de Haan P, Kalkman CJ, Jacobs MJ (2001) Pharmacologic neuroprotection in experimental spinal cord ischemia: a systematic review. J Neurosurg Anesthesiol 13:3\u201312","journal-title":"J Neurosurg Anesthesiol"},{"key":"3851_CR10","first-page":"36","volume":"26","author":"C Deng","year":"2020","unstructured":"Deng C, Chen S, Li X, Luo H, Zhang Q, Hu P, Wang F, Xiong C, Sun T, Zhang X (2020) Role of the PGE2 receptor in ischemia-reperfusion injury of the rat retina. Mol Vis 26:36\u201347","journal-title":"Mol Vis"},{"key":"3851_CR11","doi-asserted-by":"publisher","first-page":"108745","DOI":"10.1016\/j.intimp.2022.108745","volume":"108","author":"Y Dong","year":"2022","unstructured":"Dong Y, Jiang X, Chen F, Wang D, Zhang Z (2022) Inhibiting the aberrant PACT-p53 axis activation ameliorates spinal cord ischaemia\u2013reperfusion injury in rats. Int Immunopharmacol 108:108745","journal-title":"Int Immunopharmacol"},{"key":"3851_CR12","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.nbd.2019.05.009","volume":"129","author":"CR Eddings","year":"2019","unstructured":"Eddings CR, Arbez N, Akimov S, Geva M, Hayden MR, Ross CA (2019) Pridopidine protects neurons from mutant-huntingtin toxicity via the sigma-1 receptor. Neurobiol Dis 129:118\u2013129","journal-title":"Neurobiol Dis"},{"key":"3851_CR13","doi-asserted-by":"publisher","first-page":"3866","DOI":"10.3390\/ijms24043866","volume":"24","author":"Y El Ouaamari","year":"2023","unstructured":"El Ouaamari Y, Van den Bos J, Willekens B, Cools N, Wens I (2023) Neurotrophic factors as regenerative therapy for neurodegenerative diseases: current status, challenges and future perspectives. Int J Mol Sci 24:3866","journal-title":"Int J Mol Sci"},{"key":"3851_CR14","doi-asserted-by":"publisher","first-page":"703","DOI":"10.3390\/biology13090703","volume":"13","author":"MI Elmalky","year":"2024","unstructured":"Elmalky MI, Alvarez-Bolado G, Younsi A, Skutella T (2024) Axonal regeneration after spinal cord injury: molecular mechanisms, regulatory pathways, and novel strategies. Biology 13:703","journal-title":"Biology"},{"key":"3851_CR15","doi-asserted-by":"publisher","first-page":"4131","DOI":"10.3390\/ijms19124131","volume":"19","author":"JL Fletcher","year":"2018","unstructured":"Fletcher JL, Murray SS, Xiao J (2018) Brain-derived neurotrophic factor in central nervous system myelination: a new mechanism to promote myelin plasticity and repair. Int J Mol Sci 19:4131","journal-title":"Int J Mol Sci"},{"key":"3851_CR16","doi-asserted-by":"publisher","first-page":"1998","DOI":"10.1093\/brain\/awu107","volume":"137","author":"V Francardo","year":"2014","unstructured":"Francardo V, Bez F, Wieloch T, Nissbrandt H, Ruscher K, Cenci MA (2014) Pharmacological stimulation of sigma-1 receptors has neurorestorative effects in experimental parkinsonism. Brain 137:1998\u20132014","journal-title":"Brain"},{"key":"3851_CR17","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/s13311-018-00699-9","volume":"16","author":"V Francardo","year":"2019","unstructured":"Francardo V, Geva M, Bez F, Denis Q, Steiner L, Hayden MR, Cenci MA (2019) Pridopidine induces functional neurorestoration via the sigma-1 receptor in a mouse model of Parkinson\u2019s disease. Neurotherapeutics 16:465\u2013479","journal-title":"Neurotherapeutics"},{"key":"3851_CR18","doi-asserted-by":"publisher","first-page":"6956","DOI":"10.3390\/ijms22136956","volume":"22","author":"N Gaja-Capdevila","year":"2021","unstructured":"Gaja-Capdevila N, Hern\u00e1ndez N, Zamanillo D, Vela JM, Merlos M, Navarro X, Herrando-Grabulosa M (2021) Neuroprotective effects of sigma 1 receptor ligands on motoneuron death after spinal root injury in mice. Int J Mol Sci 22:6956","journal-title":"Int J Mol Sci"},{"key":"3851_CR19","doi-asserted-by":"publisher","first-page":"103258","DOI":"10.1016\/j.redox.2024.103258","volume":"75","author":"J George","year":"2024","unstructured":"George J, Lu Y, Tsuchishima M, Tsutsumi M (2024) Cellular and molecular mechanisms of hepatic ischemia-reperfusion injury: the role of oxidative stress and therapeutic approaches. Red Biol 75:103258","journal-title":"Red Biol"},{"key":"3851_CR20","doi-asserted-by":"publisher","first-page":"3975","DOI":"10.1093\/hmg\/ddw238","volume":"25","author":"M Geva","year":"2016","unstructured":"Geva M, Kusko R, Soares H, Fowler KD, Birnberg T, Barash S, Wagner AM, Fine T, Lysaght A, Weiner B (2016) Pridopidine activates neuroprotective pathways impaired in Huntington Disease. Human Mol Gen 25:3975\u20133987","journal-title":"Human Mol Gen"},{"key":"3851_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12640-017-9838-2","volume":"35","author":"N Goguadze","year":"2019","unstructured":"Goguadze N, Zhuravliova E, Morin D, Mikeladze D, Maurice T (2019) Sigma-1 receptor agonists induce oxidative stress in mitochondria and enhance complex I activity in physiological condition but protect against pathological oxidative stress. Neurotox Res 35:1\u201318","journal-title":"Neurotox Res"},{"key":"3851_CR22","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1007\/s00259-020-05030-3","volume":"48","author":"ID Grachev","year":"2021","unstructured":"Grachev ID, Meyer PM, Becker GA, Bronzel M, Marsteller D, Pastino G, Voges O, Rabinovich L, Knebel H, Zientek F, Rullmann M, Sattler B, Patt M, Gerhards T, Strauss M, Kluge A, Brust P, Savola JM, Gordon MF, Geva M, Hesse S, Barthel H, Hayden MR, Sabri O (2021) Sigma-1 and dopamine D2\/D3 receptor occupancy of pridopidine in healthy volunteers and patients with Huntington disease: a [(18)F] fluspidine and [(18)F] fallypride PET study. Eur J Nucl Med Mol Imaging 48:1103\u20131115","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"3851_CR23","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s00441-013-1774-8","volume":"356","author":"Y Ha","year":"2014","unstructured":"Ha Y, Shanmugam AK, Markand S, Zorrilla E, Ganapathy V, Smith SB (2014) Sigma receptor 1 modulates ER stress and Bcl2 in murine retina. Cell Tissue Res 356:15\u201327","journal-title":"Cell Tissue Res"},{"key":"3851_CR24","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.neulet.2010.09.007","volume":"487","author":"X Han","year":"2011","unstructured":"Han X, Yang N, Xu Y, Zhu J, Chen Z, Liu Z, Dang G, Song C (2011) Simvastatin treatment improves functional recovery after experimental spinal cord injury by upregulating the expression of BDNF and GDNF. Neurosci Lett 487:255\u2013259","journal-title":"Neurosci Lett"},{"key":"3851_CR25","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1080\/15321819.2021.1914085","volume":"42","author":"SM Hazzaa","year":"2021","unstructured":"Hazzaa SM, Abdou AG, Ibraheim EO, Salem EA, Hassan MHA, Abdel-Razek HAD (2021) Effect of L-carnitine and atorvastatin on a rat model of ischemia-reperfusion injury of spinal cord. J Immunoassay Immunochem 42:596\u2013619","journal-title":"J Immunoassay Immunochem"},{"key":"3851_CR26","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41392-023-01477-6","volume":"8","author":"X Hu","year":"2023","unstructured":"Hu X, Xu W, Ren Y, Wang Z, He X, Huang R, Ma B, Zhao J, Zhu R, Cheng L (2023) Spinal cord injury: molecular mechanisms and therapeutic interventions. Signal Transd Target Ther 8:245","journal-title":"Signal Transd Target Ther"},{"key":"3851_CR27","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41419-019-1451-2","volume":"10","author":"A Ionescu","year":"2019","unstructured":"Ionescu A, Gradus T, Altman T, Maimon R, Saraf Avraham N, Geva M, Hayden M, Perlson E (2019) Targeting the sigma-1 receptor via pridopidine ameliorates central features of ALS pathology in a SOD1G93A model. Cell Death Dis 10:210","journal-title":"Cell Death Dis"},{"key":"3851_CR28","doi-asserted-by":"publisher","first-page":"e287","DOI":"10.1016\/j.wneu.2021.02.129","volume":"150","author":"R Kahveci","year":"2021","unstructured":"Kahveci R, Kahveci FO, Gokce EC, Gokce A, K\u0131sa \u00dc, Sargon MF, Fesli R, G\u00fcrer B (2021) Effects of Ganoderma lucidum polysaccharides on different pathways involved in the development of spinal cord ischemia reperfusion injury: biochemical, histopathologic, and ultrastructural analysis in a rat model. World Neurosurg 150:e287\u2013e297","journal-title":"World Neurosurg"},{"key":"3851_CR29","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1007\/s11064-024-04282-x","volume":"50","author":"SA Khodir","year":"2024","unstructured":"Khodir SA, Sweed EM, Faried MA, Abo Elkhair DM, Khalil MM, Afifi KH, El Agamy DF (2024) Neuroprotective effect of maresin-1 in rotenone-induced Parkinson\u2019s disease in rats: The putative role of the JAK\/STAT pathway. Neurochem Res 50:30","journal-title":"Neurochem Res"},{"key":"3851_CR30","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1074\/mcp.M600157-MCP200","volume":"5","author":"FH Kobeissy","year":"2006","unstructured":"Kobeissy FH, Ottens AK, Zhang Z, Liu MC, Denslow ND, Dave JR, Tortella FC, Hayes RL, Wang KK (2006) Novel differential neuroproteomics analysis of traumatic brain injury in rats. Mol Cell Proteomics 5:1887\u20131898","journal-title":"Mol Cell Proteomics"},{"key":"3851_CR31","doi-asserted-by":"publisher","first-page":"100254","DOI":"10.1016\/j.wnsx.2023.100254","volume":"21","author":"P Kuru Bekta\u015fo\u011flu","year":"2024","unstructured":"Kuru Bekta\u015fo\u011flu P, Ar\u0131k\u00f6k AT, Erg\u00fcder B, Sargon MF, Altun SA, \u00dcnl\u00fcler C, B\u00f6rekci A, Kertmen H, \u00c7eliko\u011flu E, G\u00fcrer B (2024) Cinnamaldehyde has ameliorative effects on rabbit spinal cord ischemia and reperfusion injury. World Neurosurg X 21:100254","journal-title":"World Neurosurg X"},{"key":"3851_CR32","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.3390\/ijms24031971","volume":"24","author":"V Lachance","year":"2023","unstructured":"Lachance V, B\u00e9langer SM, Hay C, Le Corvec V, Banouvong V, Lapalme M, Tarmoun K, Beaucaire G, Lussier MP, Kourrich S (2023) Overview of sigma-1R subcellular specific biological functions and role in neuroprotection. Int J Mol Sci 24:1971","journal-title":"Int J Mol Sci"},{"key":"3851_CR33","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/1749-8090-8-64","volume":"8","author":"G Lafci","year":"2013","unstructured":"Lafci G, Gedik HS, Korkmaz K, Erdem H, Cicek OF, Nacar OA, Yildirim L, Kaya E, Ankarali H (2013) Efficacy of iloprost and montelukast combination on spinal cord ischemia\/reperfusion injury in a rat model. J Cardiothorac Surg 8:64","journal-title":"J Cardiothorac Surg"},{"key":"3851_CR34","doi-asserted-by":"publisher","first-page":"105857","DOI":"10.1016\/j.nbd.2022.105857","volume":"173","author":"S Lenoir","year":"2022","unstructured":"Lenoir S, Lahaye RA, Vitet H, Scaramuzzino C, Virlogeux A, Capellano L, Genoux A, Gershoni-Emek N, Geva M, Hayden MR, Saudou F (2022) Pridopidine rescues BDNF\/TrkB trafficking dynamics and synapse homeostasis in a Huntington disease brain-on-a-chip model. Neurobiol Dis 173:105857","journal-title":"Neurobiol Dis"},{"key":"3851_CR35","first-page":"4837","volume":"8","author":"H Li","year":"2015","unstructured":"Li H, Jia Z, Li G, Zhao X, Sun P, Wang J, Fan Z, Lv G (2015) Neuroprotective effects of exendin-4 in rat model of spinal cord injury via inhibiting mitochondrial apoptotic pathway. Int J Clin Exp Pathol 8:4837","journal-title":"Int J Clin Exp Pathol"},{"key":"3851_CR36","doi-asserted-by":"publisher","first-page":"986443","DOI":"10.3389\/fnagi.2022.986443","volume":"14","author":"Y Li","year":"2022","unstructured":"Li Y, Li F, Qin D, Chen H, Wang J, Wang J, Song S, Wang C, Wang Y, Liu S, Gao D, Wang ZH (2022) The role of brain derived neurotrophic factor in central nervous system. Front Aging Neurosci 14:986443","journal-title":"Front Aging Neurosci"},{"key":"3851_CR37","doi-asserted-by":"publisher","first-page":"111382","DOI":"10.1016\/j.intimp.2023.111382","volume":"127","author":"Z Li","year":"2024","unstructured":"Li Z, Zhou J, Cui S, Hu S, Li B, Liu X, Zhang C, Zou Y, Hu Y, Yu Y, Shen B, Yang B (2024) Activation of sigma-1 receptor ameliorates sepsis-induced myocardial injury by mediating the Nrf2\/HO1 signaling pathway to attenuate mitochondrial oxidative stress. Int Immunopharmacol 127:111382","journal-title":"Int Immunopharmacol"},{"key":"3851_CR38","doi-asserted-by":"publisher","first-page":"BSR20211399","DOI":"10.1042\/BSR20211399","volume":"42","author":"KP Liu","year":"2022","unstructured":"Liu KP, Ma W, Li CY, Li LY (2022) Neurotrophic factors combined with stem cells in the treatment of sciatic nerve injury in rats: a meta-analysis. Biosci Rep 42:BSR20211399","journal-title":"Biosci Rep"},{"key":"3851_CR39","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.3390\/jpm12101629","volume":"12","author":"F Marturano","year":"2022","unstructured":"Marturano F, Nisi F, Giustiniano E, Benedetto F, Piccioni F, Ripani U (2022) Prevention of spinal cord injury during thoracoabdominal aortic aneurysms repair: what the anaesthesiologist should know. J Pers Med 12:1629","journal-title":"J Pers Med"},{"key":"3851_CR40","doi-asserted-by":"publisher","first-page":"e76941","DOI":"10.1371\/journal.pone.0076941","volume":"8","author":"T Mori","year":"2013","unstructured":"Mori T, Hayashi T, Hayashi E, Su TP (2013) Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival. PLoS One 8:e76941","journal-title":"PLoS One"},{"key":"3851_CR41","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1111\/j.1471-4159.2011.07256.x","volume":"117","author":"S Moriguchi","year":"2011","unstructured":"Moriguchi S, Yamamoto Y, Ikuno T, Fukunaga K (2011) Sigma-1 receptor stimulation by dehydroepiandrosterone ameliorates cognitive impairment through activation of CaM kinase II, protein kinase C and extracellular signal-regulated kinase in olfactory bulbectomized mice. J Neurochem 117:879\u2013891","journal-title":"J Neurochem"},{"key":"3851_CR42","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/1423-0127-17-55","volume":"17","author":"MD Morsy","year":"2010","unstructured":"Morsy MD, Mostafa OA, Hassan WN (2010) A potential protective effect of \u03b1-tocopherol on vascular complication in spinal cord reperfusion injury in rats. J Biomed Sci 17:55","journal-title":"J Biomed Sci"},{"key":"3851_CR43","doi-asserted-by":"publisher","first-page":"105803","DOI":"10.1016\/j.biocel.2020.105803","volume":"126","author":"ZY Motawe","year":"2020","unstructured":"Motawe ZY, Abdelmaboud SS, Cuevas J, Breslin JW (2020) PRE-084 as a tool to uncover potential therapeutic applications for selective sigma-1 receptor activation. Int J Biochem Cell Biol 126:105803","journal-title":"Int J Biochem Cell Biol"},{"key":"3851_CR44","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.3390\/ijms24031997","volume":"24","author":"FJ Munguia-Galaviz","year":"2023","unstructured":"Munguia-Galaviz FJ, Miranda-Diaz AG, Cardenas-Sosa MA, Echavarria R (2023) Sigma-1 receptor signaling: in search of new therapeutic alternatives for cardiovascular and renal diseases. Int J Mol Sci 24:1997","journal-title":"Int J Mol Sci"},{"key":"3851_CR45","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1007\/s13311-021-01022-9","volume":"18","author":"L Naia","year":"2021","unstructured":"Naia L, Ly P, Mota SI, Lopes C, Maranga C, Coelho P, Gershoni-Emek N, Ankarcrona M, Geva M, Hayden MR, Rego AC (2021) The sigma-1 receptor mediates pridopidine rescue of mitochondrial function in Huntington disease models. Neurotherapeutics 18:1017\u20131038","journal-title":"Neurotherapeutics"},{"key":"3851_CR46","doi-asserted-by":"publisher","first-page":"104672","DOI":"10.1016\/j.neuint.2020.104672","volume":"134","author":"T Nishihara","year":"2020","unstructured":"Nishihara T, Tanaka J, Sekiya K, Nishikawa Y, Abe N, Hamada T, Kitamura S, Ikemune K, Ochi S, Choudhury ME, Yano H, Yorozuya T (2020) Chronic constriction injury of the sciatic nerve in rats causes different activation modes of microglia between the anterior and posterior horns of the spinal cord. Neurochem Int 134:104672","journal-title":"Neurochem Int"},{"key":"3851_CR47","doi-asserted-by":"publisher","first-page":"595","DOI":"10.33549\/physiolres.930100","volume":"50","author":"I Pek\u00e1rkov\u00e1","year":"2001","unstructured":"Pek\u00e1rkov\u00e1 I, Parara S, Holecek V, Stopka P, Trefil L, Racek J, Rokyta R (2001) Does exogenous melatonin influence the free radicals metabolism and pain sensation in rat? Physiol Res 50:595\u2013602","journal-title":"Physiol Res"},{"key":"3851_CR48","first-page":"97","volume":"16","author":"B Penke","year":"2018","unstructured":"Penke B, Fulop L, Szucs M, Frecska E (2018) The role of sigma-1 receptor, an intracellular chaperone in neurodegenerative diseases. Curr Neuropharmacol 16:97\u2013116","journal-title":"Curr Neuropharmacol"},{"key":"3851_CR49","doi-asserted-by":"publisher","first-page":"3617","DOI":"10.1111\/bph.15193","volume":"177","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M, Garner P, Holgate ST, Howells DW, Karp NA, Lazic SE, Lidster K, MacCallum CJ, Macleod M, Pearl EJ, Petersen OH, Rawle F, Reynolds P, Rooney K, Sena ES, Silberberg SD, Steckler T, W\u00fcrbel H (2020) The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. British journal of pharmacology 177:3617\u20133624","journal-title":"British journal of pharmacology"},{"key":"3851_CR50","doi-asserted-by":"publisher","first-page":"777","DOI":"10.32598\/bcn.2021.1727.1","volume":"12","author":"S Pourkhodadad","year":"2021","unstructured":"Pourkhodadad S, Oryan S, Hadipour MM, Kaka G, Sadraie SH (2021) Minocycline enhance the restorative ability of olfactory ensheathing cells by the upregulation of BDNF and GDNF expression after spinal cord injury. Basic Clin Neurosci 12:777\u2013788","journal-title":"Basic Clin Neurosci"},{"key":"3851_CR51","doi-asserted-by":"publisher","first-page":"165","DOI":"10.3390\/antiox11010165","volume":"11","author":"LR Rodr\u00edguez","year":"2022","unstructured":"Rodr\u00edguez LR, Lape\u00f1a-Luz\u00f3n T, Benet\u00f3 N, Beltran-Beltran V, Pallard\u00f3 FV, Gonzalez-Cabo P, Navarro JA (2022) Therapeutic strategies targeting mitochondrial calcium signaling: a new hope for neurological diseases? Antioxidants (Basel) 11:165","journal-title":"Antioxidants (Basel)"},{"key":"3851_CR52","doi-asserted-by":"publisher","first-page":"15200","DOI":"10.3390\/ijms242015200","volume":"24","author":"R Roy","year":"2023","unstructured":"Roy R, Wilcox J, Webb AJ, O\u2019Gallagher K (2023) Dysfunctional and dysregulated nitric oxide synthases in cardiovascular disease: mechanisms and therapeutic potential. Int J Mol Sci 24:15200","journal-title":"Int J Mol Sci"},{"key":"3851_CR53","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.nbd.2016.10.006","volume":"97","author":"D Ryskamp","year":"2017","unstructured":"Ryskamp D, Wu J, Geva M, Kusko R, Grossman I, Hayden M, Bezprozvanny I (2017) The sigma-1 receptor mediates the beneficial effects of pridopidine in a mouse model of Huntington disease. Neurobiol Dis 97:46\u201359","journal-title":"Neurobiol Dis"},{"key":"3851_CR54","doi-asserted-by":"publisher","first-page":"474181","DOI":"10.3389\/fnins.2019.00862","volume":"13","author":"DA Ryskamp","year":"2019","unstructured":"Ryskamp DA, Korban S, Zhemkov V, Kraskovskaya N, Bezprozvanny I (2019) Neuronal sigma-1 receptors: signaling functions and protective roles in neurodegenerative diseases. Front Neurosci 13:474181","journal-title":"Front Neurosci"},{"key":"3851_CR55","doi-asserted-by":"publisher","first-page":"22","DOI":"10.21037\/jeccm.2019.04.03","volume":"3","author":"EC S\u00e1nchez","year":"2019","unstructured":"S\u00e1nchez EC (2019) Pathophysiology of ischemia-reperfusion injury and its management with hyperbaric oxygen (HBO): a review. J Emergency Critic Care Med 3:22","journal-title":"J Emergency Critic Care Med"},{"key":"3851_CR56","doi-asserted-by":"publisher","first-page":"2025756","DOI":"10.1155\/2022\/2025756","volume":"2022","author":"X Shen","year":"2022","unstructured":"Shen X, Zhang Y, Zhu H, Sun Y, Wang W, Zhou Z, Li C (2022) Triad1 promotes the inflammatory response and neuronal apoptosis to aggravate acute spinal cord injury in rats. Comput Math Methods Med 2022:2025756","journal-title":"Comput Math Methods Med"},{"key":"3851_CR57","doi-asserted-by":"publisher","first-page":"136","DOI":"10.3390\/ijms22010136","volume":"22","author":"S Stanga","year":"2021","unstructured":"Stanga S, Boido M, Kienlen-Campard P (2021) How to build and to protect the neuromuscular junction: the role of the glial cell line-derived neurotrophic factor. Int J Mol Sci 22:136","journal-title":"Int J Mol Sci"},{"key":"3851_CR58","doi-asserted-by":"publisher","first-page":"e106533","DOI":"10.1371\/journal.pone.0106533","volume":"9","author":"A Szabo","year":"2014","unstructured":"Szabo A, Kovacs A, Frecska E, Rajnavolgyi E (2014) Psychedelic N, N-dimethyltryptamine and 5-methoxy-N, N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. PLoS One 9:e106533","journal-title":"PLoS One"},{"key":"3851_CR59","doi-asserted-by":"publisher","first-page":"149011","DOI":"10.1016\/j.brainres.2024.149011","volume":"1838","author":"R Tan","year":"2024","unstructured":"Tan R, Sui C, Diao Y, Shi G, Hu X, Hao Z, Li C, Hao M, Xie M, Zhu T (2024) Activation of the sigma-1 receptor ameliorates neuronal ferroptosis via IRE1\u03b1 after spinal cord injury. Brain Res 1838:149011","journal-title":"Brain Res"},{"key":"3851_CR60","doi-asserted-by":"publisher","first-page":"387","DOI":"10.4103\/0028-3886.55583","volume":"57","author":"J Tang","year":"2009","unstructured":"Tang J, Hua Y, Su J, Zhang P, Zhu X, Wu L, Niu Q, Xiao H, Ding X (2009) Expression of VEGF and neural repair after alprostadil treatment in a rat model of sciatic nerve crush injury. Neurol India 57:387\u2013394","journal-title":"Neurol India"},{"key":"3851_CR61","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1093\/procel\/pwad003","volume":"14","author":"T Tian","year":"2023","unstructured":"Tian T, Zhang S, Yang M (2023) Recent progress and challenges in the treatment of spinal cord injury. Protein Cell 14:635\u2013652","journal-title":"Protein Cell"},{"key":"3851_CR62","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.freeradbiomed.2016.12.014","volume":"103","author":"L Wang","year":"2017","unstructured":"Wang L, Yao Y, He R, Meng Y, Li N, Zhang D, Xu J, Chen O, Cui J, Bian J, Zhang Y, Chen G, Deng X (2017) Methane ameliorates spinal cord ischemia-reperfusion injury in rats: antioxidant, anti-inflammatory and anti-apoptotic activity mediated by Nrf2 activation. Free Rad Biol Med 103:69\u201386","journal-title":"Free Rad Biol Med"},{"key":"3851_CR63","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.freeradbiomed.2019.02.001","volume":"134","author":"J Wang","year":"2019","unstructured":"Wang J, Zhao J, Cui X, Mysona BA, Navneet S, Saul A, Ahuja M, Lambert N, Gazaryan IG, Thomas B, Bollinger KE, Smith SB (2019) The molecular chaperone sigma 1 receptor mediates rescue of retinal cone photoreceptor cells via modulation of NRF2. Free Radic Biol Med 134:604\u2013616","journal-title":"Free Radic Biol Med"},{"key":"3851_CR64","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1080\/15548627.2022.2063003","volume":"19","author":"SM Wang","year":"2023","unstructured":"Wang SM, Wu HE, Yasui Y, Geva M, Hayden M, Maurice T, Cozzolino M, Su TP (2023) Nucleoporin POM121 signals TFEB-mediated autophagy via activation of SIGMAR1\/sigma-1 receptor chaperone by pridopidine. Autophagy 19:126\u2013151","journal-title":"Autophagy"},{"key":"3851_CR65","doi-asserted-by":"publisher","first-page":"1254600","DOI":"10.3389\/fnins.2024.1254600","volume":"18","author":"X-x Wang","year":"2024","unstructured":"Wang X-x, Li G-S, Wang K-H, Hu X-S, Hu Y (2024) Positive effect of microvascular proliferation on functional recovery in experimental cervical spondylotic myelopathy. Front Neurosci 18:1254600","journal-title":"Front Neurosci"},{"key":"3851_CR66","doi-asserted-by":"publisher","first-page":"5649","DOI":"10.1007\/s12035-021-02524-5","volume":"58","author":"NH Wu","year":"2021","unstructured":"Wu NH, Ye Y, Wan BB, Yu YD, Liu C, Chen QJ (2021) Emerging benefits: pathophysiological functions and target drugs of the sigma-1 receptor in neurodegenerative diseases. Mol Neurobiol 58:5649\u20135666","journal-title":"Mol Neurobiol"},{"key":"3851_CR67","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s12964-023-01457-x","volume":"22","author":"L Xie","year":"2024","unstructured":"Xie L, Wu H, He Q, Shi W, Zhang J, Xiao X, Yu T (2024) A slow-releasing donor of hydrogen sulfide inhibits neuronal cell death via anti-PANoptosis in rats with spinal cord ischemia-reperfusion injury. Cell Commun Signal 22:33","journal-title":"Cell Commun Signal"},{"key":"3851_CR68","doi-asserted-by":"publisher","first-page":"9556","DOI":"10.18632\/aging.102404","volume":"11","author":"M Zhai","year":"2019","unstructured":"Zhai M, Liu C, Li Y, Zhang P, Yu Z, Zhu H, Zhang L, Zhang Q, Wang J, Wang J (2019) Dexmedetomidine inhibits neuronal apoptosis by inducing sigma-1 receptor signaling in cerebral ischemia-reperfusion injury. Aging (Albany NY) 11:9556\u20139568","journal-title":"Aging (Albany NY)"},{"key":"3851_CR69","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.4103\/1673-5374.339471","volume":"17","author":"ZL Zhang","year":"2022","unstructured":"Zhang ZL, Wang D, Chen FS (2022) MicroRNA-101a-3p mimic ameliorates spinal cord ischemia\/reperfusion injury. Neural Regen Res 17:2022\u20132028","journal-title":"Neural Regen Res"},{"key":"3851_CR70","doi-asserted-by":"publisher","first-page":"1049562","DOI":"10.3389\/fncel.2022.1049562","volume":"16","author":"Q Zhao","year":"2022","unstructured":"Zhao Q, Zhu Y, Ren Y, Yin S, Yu L, Huang R, Song S, Hu X, Zhu R, Cheng L, Xie N (2022) Neurogenesis potential of oligodendrocyte precursor cells from oligospheres and injured spinal cord. Front Cell Neurosci 16:1049562","journal-title":"Front Cell Neurosci"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-03851-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-025-03851-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-03851-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T05:38:11Z","timestamp":1757137091000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-025-03851-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,12]]},"references-count":70,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["3851"],"URL":"https:\/\/doi.org\/10.1007\/s00210-025-03851-3","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,12]]},"assertion":[{"value":"18 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 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 current study was authorized by the ethics committee of the Faculty of Medicine, Menoufia University, Egypt and consented to by the national ethics committee with IRB No 9-2024 BIO9.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}