{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:25:46Z","timestamp":1790699146014,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Internal Paracelsus Medical University RISE Funding","award":["R-15\/05\/072-FOD"],"award-info":[{"award-number":["R-15\/05\/072-FOD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bladder dysfunction is among the most drastic and quality-of-life-reducing conditions after spinal cord injury (SCI). Neuroinflammation in the lower urinary tract (LUT) after SCI could be a key driver of neurogenic bladder dysfunction and tissue fibrosis. Leukotrienes, a group of highly active lipid mediators, are potent inflammatory mediators. Here, we explored the potential of early montelukast (MLK) therapy, a cysteinyl leukotriene receptor 1 antagonist, on LUT function and structure four weeks after severe SCI in rats. Rats (strain Lewis, female, n = 50) received a permanent bladder catheter, followed by a complete T9 spinal cord transection. MLK was given daily, starting on day one post-injury. Bladder and locomotor function were regularly assessed. Bladder tissue was histologically and immunhistochemically analyzed. Post-SCI, MLK concentrations in plasma and cerebrospinal fluid were clinically relevant. MLK improved bladder functionality. MLK had no impact on smooth muscle alignment and uroepithelial integrity at this early SCI time point. This pilot study gave first insights into early, continuous oral MLK treatment with the first promising results of preserved LUT function and possible subsequent improved tissue integrity.<\/jats:p>","DOI":"10.3390\/ijms26125606","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T11:18:40Z","timestamp":1749640720000},"page":"5606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Montelukast Improves Urinary Bladder Function After Complete Spinal Cord Injury in Rats"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4560-1515","authenticated-orcid":false,"given":"Elena E.","family":"Keller","sequence":"first","affiliation":[{"name":"Institute of Molecular and Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9342-4251","authenticated-orcid":false,"given":"Sophina","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Urology and Andrology, University Hospital Salzburg, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2792-3904","authenticated-orcid":false,"given":"Karin","family":"Roider","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4057-0246","authenticated-orcid":false,"given":"Michael","family":"Kleindorfer","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria"},{"name":"Department of Urology and Andrology, University Hospital Salzburg, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0661-388X","authenticated-orcid":false,"given":"Peter","family":"T\u00f6rzs\u00f6k","sequence":"additional","affiliation":[{"name":"Faculty of Health and Sport Sciences, Sz\u00e9chenyi Istv\u00e1n University, 9026 Gy\u0151r, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0195-2619","authenticated-orcid":false,"given":"Julia","family":"Tevini","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Paracelsus Medical University, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8266-5513","authenticated-orcid":false,"given":"Thomas","family":"Felder","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Paracelsus Medical University, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1653-8046","authenticated-orcid":false,"given":"Ludwig","family":"Aigner","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5284-7276","authenticated-orcid":false,"given":"Lukas","family":"Lusuardi","sequence":"additional","affiliation":[{"name":"Department of Urology and Andrology, University Hospital Salzburg, M\u00fcllner Hauptstrasse 48, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.urology.2017.03.006","article-title":"Urologic Management and Complications in Spinal Cord Injury Patients: A 40- to 50-year Follow-up Study","volume":"104","author":"Gao","year":"2017","journal-title":"Urology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1100\/tsw.2011.26","article-title":"Spinal cord injury and bladder dysfunction: New ideas about an old problem","volume":"11","author":"Cruz","year":"2011","journal-title":"Sci. World J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/ana.21814","article-title":"Early sacral neuromodulation prevents urinary incontinence after complete spinal cord injury","volume":"67","author":"Sievert","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/bju.13039","article-title":"A novel urodynamic model for lower urinary tract assessment in awake rats","volume":"115","author":"Schneider","year":"2015","journal-title":"BJU Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.eururo.2009.04.028","article-title":"EAU guidelines on neurogenic lower urinary tract dysfunction","volume":"56","author":"Stohrer","year":"2009","journal-title":"Eur. Urol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1055\/s-0040-1713876","article-title":"Neurogenic Bladder: Epidemiology, Diagnosis, and Management","volume":"40","author":"Panicker","year":"2020","journal-title":"Semin. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.cnr.2006.09.007","article-title":"Inflammation and Spinal Cord Injury: Infiltrating Leukocytes as Determinants of Injury and Repair Processes","volume":"6","author":"Trivedi","year":"2006","journal-title":"Clin. Neurosci. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kwiecien, J.M., Dabrowski, W., Dabrowska-Bouta, B., Sulkowski, G., Oakden, W., Kwiecien-Delaney, C.J., Yaron, J.R., Zhang, L., Schutz, L., and Marzec-Kotarska, B. (2020). Prolonged inflammation leads to ongoing damage after spinal cord injury. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0226584"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3303","DOI":"10.1111\/bph.16408","article-title":"Montelukast improves disease outcome in SOD1(G93A) female mice by counteracting oligodendrocyte dysfunction and aberrant glial reactivity","volume":"181","author":"Raffaele","year":"2024","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wognum, S., Lagoa, C.E., Nagatomi, J., Sacks, M.S., and Vodovotz, Y. (2009). An exploratory pathways analysis of temporal changes induced by spinal cord injury in the rat bladder wall: Insights on remodeling and inflammation. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005852"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00281-018-0674-0","article-title":"Role of neurogenic inflammation in local communication in the visceral mucosa","volume":"40","author":"Birder","year":"2018","journal-title":"Semin. Immunopathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1186\/s12974-016-0736-y","article-title":"Multiple organ dysfunction and systemic inflammation after spinal cord injury: A complex relationship","volume":"13","author":"Sun","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/nau.22619","article-title":"S-Nitrosoglutathione protects the spinal bladder: Novel therapeutic approach to post-spinal cord injury bladder remodeling","volume":"34","author":"Shunmugavel","year":"2014","journal-title":"Neurourol. Urodyn."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1476-9255-7-17","article-title":"Simvastatin protects bladder and renal functions following spinal cord injury in rats","volume":"7","author":"Shunmugavel","year":"2010","journal-title":"J. Inflamm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.prp.2011.10.004","article-title":"The ameliorating effect of dantrolene on the morphology of urinary bladder in spinal cord injured rats","volume":"207","author":"Torres","year":"2011","journal-title":"Pathol. Res. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.jss.2013.02.016","article-title":"Beneficial effects of quercetin on rat urinary bladder after spinal cord injury","volume":"183","author":"Cevik","year":"2013","journal-title":"J. Surg. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.4049\/jimmunol.173.3.1503","article-title":"Cysteinyl leukotrienes and their receptors: Cellular distribution and function in immune and inflammatory responses","volume":"173","author":"Kanaoka","year":"2004","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3454212","DOI":"10.1155\/2017\/3454212","article-title":"Cysteinyl Leukotrienes as Potential Pharmacological Targets for Cerebral Diseases","volume":"2017","author":"Gelosa","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/cns.12596","article-title":"Cysteinyl Leukotrienes and Their Receptors: Emerging Therapeutic Targets in Central Nervous System Disorders","volume":"22","author":"Ghosh","year":"2016","journal-title":"CNS Neurosci. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0022-5347(06)00513-1","article-title":"Cysteinyl leukotriene D4 increases human detrusor muscle responsiveness to histamine","volume":"176","author":"Bouchelouche","year":"2006","journal-title":"J. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1046\/j.1464-410x.2001.02135.x","article-title":"The action of cysteinyl-leukotrienes on intracellular calcium mobilization in human detrusor myocytes","volume":"87","author":"Bouchelouche","year":"2001","journal-title":"BJU Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/S0091-6749(96)70086-6","article-title":"Effects of montelukast (MK-0476), a new potent cysteinyl leukotriene (LTD4) receptor antagonist, in patients with chronic asthma","volume":"98","author":"Reiss","year":"1996","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1016\/S0022-5347(05)65663-7","article-title":"The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis","volume":"166","author":"Bouchelouche","year":"2001","journal-title":"J. Urol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e49","DOI":"10.1345\/aph.1Q130","article-title":"Montelukast for symptom control of interstitial cystitis","volume":"45","author":"Traut","year":"2011","journal-title":"Ann. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.prostaglandins.2012.09.002","article-title":"Montelukast inhibits caspase-3 activity and ameliorates oxidative damage in the spinal cord and urinary bladder of rats with spinal cord injury","volume":"99","author":"Ersahin","year":"2012","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Freyermuth-Trujillo, X., Segura-Uribe, J.J., Salgado-Ceballos, H., Orozco-Barrios, C.E., and Coyoy-Salgado, A. (2022). Inflammation: A Target for Treatment in Spinal Cord Injury. Cells, 11.","DOI":"10.3390\/cells11172692"},{"key":"ref_27","first-page":"524","article-title":"Increased production of eicosanoids, TXA2, PGI2 and LTC4 in experimental spinal cord injuries","volume":"32","author":"Mitsuhashi","year":"1994","journal-title":"Paraplegia"},{"key":"ref_28","first-page":"950","article-title":"Experimental and clinical studies of eicosanoids in cerebrospinal fluid after spinal cord injury","volume":"39","author":"Nishisho","year":"1996","journal-title":"Neurosurgery"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/sj.bjp.0707577","article-title":"Effects of zileuton and montelukast in mouse experimental spinal cord injury","volume":"153","author":"Genovese","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8466","DOI":"10.1038\/ncomms9466","article-title":"Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug","volume":"6","author":"Marschallinger","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Michael, J., Bessa de Sousa, D., Conway, J., Gonzalez-Labrada, E., Obeid, R., Tevini, J., Felder, T., Hutter-Paier, B., Zerbe, H., and Paiement, N. (2020). Improved Bioavailability of Montelukast through a Novel Oral Mucoadhesive Film in Humans and Mice. Pharmaceutics, 13.","DOI":"10.1101\/2020.11.06.371500"},{"key":"ref_32","first-page":"e56506","article-title":"Cystometric and External Urethral Sphincter Measurements in Awake Rats with Implanted Catheter and Electrodes Allowing for Repeated Measurements","volume":"131","author":"Foditsch","year":"2018","journal-title":"J. Vis. Exp. JoVE"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/neu.1995.12.1","article-title":"A sensitive and reliable locomotor rating scale for open field testing in rats","volume":"12","author":"Basso","year":"1995","journal-title":"J. Neurotrauma"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1002\/bmc.3114","article-title":"Sensitive LC-MS\/MS-ESI method for simultaneous determination of montelukast and fexofenadine in human plasma: Application to a bioequivalence study","volume":"28","author":"Muppavarapu","year":"2014","journal-title":"Biomed. Chromatogr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3797\/scipharm.1002-07","article-title":"Method development and validation of montelukast in human plasma by HPLC coupled with ESI-MS\/MS: Application to a bioequivalence study","volume":"78","author":"Challa","year":"2010","journal-title":"Sci. Pharm."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5606\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:50:18Z","timestamp":1760032218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5606"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125606"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125606","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,11]]}}}