{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T21:04:20Z","timestamp":1767474260369,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"i3S","award":["UI\/BD\/151547\/2021","SFRH\/BD\/135868\/2018"],"award-info":[{"award-number":["UI\/BD\/151547\/2021","SFRH\/BD\/135868\/2018"]}]},{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia Tecnologia","award":["UI\/BD\/151547\/2021","SFRH\/BD\/135868\/2018"],"award-info":[{"award-number":["UI\/BD\/151547\/2021","SFRH\/BD\/135868\/2018"]}]},{"name":"Santa Casa da Miseric\u00f3rdia de Lisboa","award":["UI\/BD\/151547\/2021","SFRH\/BD\/135868\/2018"],"award-info":[{"award-number":["UI\/BD\/151547\/2021","SFRH\/BD\/135868\/2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic spinal cord injury (SCI) results in the time-dependent development of urinary impairment due to neurogenic detrusor overactivity (NDO) and detrusor-sphincter-dyssynergia (DSD). This is known to be accompanied by massive changes in the bladder wall. It is presently less clear if the urethra wall also undergoes remodelling. To investigate this issue, female rats were submitted to complete spinal transection at the T8\/T9 level and left to recover for 1 week and 4 weeks. To confirm the presence of SCI-induced NDO, bladder function was assessed by cystometry under urethane anesthesia before euthanasia. Spinal intact animals were used as controls. Urethras were collected and processed for further analysis. Following thoracic SCI, time-dependent changes in the urethra wall were observed. Histological assessment revealed marked urethral epithelium reorganization in response to SCI, as evidenced by an increase in epithelial thickness. At the muscular layer, SCI resulted in strong atrophy of the smooth muscle present in the urethral sphincter. Innervation was also affected, as evidenced by a pronounced decrease in the expression of markers of general innervation, particularly those present in sensory and sympathetic nerve fibres. The present data show an evident impact of SCI on the urethra, with significant histological rearrangement, accompanied by sensory and sympathetic denervation. It is likely that these changes will affect urethral function and contribute to SCI-induced urinary dysfunction, and they deserve further investigation.<\/jats:p>","DOI":"10.3390\/ijms232415951","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T03:01:51Z","timestamp":1671073311000},"page":"15951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Spinal Cord Injury Causes Marked Tissue Rearrangement in the Urethra\u2014Experimental Study in the Rat"],"prefix":"10.3390","volume":"23","author":[{"given":"Ana","family":"Ferreira","sequence":"first","affiliation":[{"name":"Experimental Biology Unit, Department of Biomedicine, Faculty of Medicine of Porto, University of Porto, 4200-319 Porto, Portugal"},{"name":"Translational Neurourology, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade-i3S, IBMC, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3311-7187","authenticated-orcid":false,"given":"S\u00edlvia Sousa","family":"Chambel","sequence":"additional","affiliation":[{"name":"Experimental Biology Unit, Department of Biomedicine, Faculty of Medicine of Porto, University of Porto, 4200-319 Porto, Portugal"},{"name":"Translational Neurourology, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade-i3S, IBMC, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5842-643X","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Avelino","sequence":"additional","affiliation":[{"name":"Experimental Biology Unit, Department of Biomedicine, Faculty of Medicine of Porto, University of Porto, 4200-319 Porto, Portugal"},{"name":"Translational Neurourology, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade-i3S, IBMC, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8922-5713","authenticated-orcid":false,"given":"C\u00e9lia Duarte","family":"Cruz","sequence":"additional","affiliation":[{"name":"Experimental Biology Unit, Department of Biomedicine, Faculty of Medicine of Porto, University of Porto, 4200-319 Porto, Portugal"},{"name":"Translational Neurourology, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade-i3S, IBMC, University of Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/nau.20761","article-title":"Changes in afferent activity after spinal cord injury","volume":"29","author":"Yoshimura","year":"2010","journal-title":"Neurourol. Urodyn."},{"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":"1565","DOI":"10.1016\/j.juro.2018.01.046","article-title":"Detrusor Acontractility after Acute Spinal Cord Injury-Myth or Reality?","volume":"199","author":"Bywater","year":"2018","journal-title":"J. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/sj.sc.3101603","article-title":"Spinal shock revisited: A four-phase model","volume":"42","author":"Ditunno","year":"2004","journal-title":"Spinal Cord"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Anjum, A., Yazid, M.D., Fauzi Daud, M., Idris, J., Ng, A.M.H., Selvi Naicker, A., Ismail, O.H.R., Athi Kumar, R.K., and Lokanathan, Y. (2020). Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207533"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.pneurobio.2013.11.002","article-title":"From basics to clinical: A comprehensive review on spinal cord injury","volume":"114","author":"Silva","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0079-6123(05)52005-3","article-title":"Mechanisms underlying the recovery of lower urinary tract function following spinal cord injury","volume":"152","author":"Yoshimura","year":"2006","journal-title":"Prog. Brain Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Chambel, S.S., Ferreira, A., Oliveira, R., Miranda, R., Vale, L., Reguenga, C., Schwab, M.E., and Cruz, C.D. (2022). Development of Neurogenic Detrusor Overactivity after Thoracic Spinal Cord Injury Is Accompanied by Time-Dependent Changes in Lumbosacral Expression of Axonal Growth Regulators. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158667"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/S1474-4422(15)00070-8","article-title":"Lower urinary tract dysfunction in the neurological patient: Clinical assessment and management","volume":"14","author":"Panicker","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.eururo.2015.07.071","article-title":"Summary of European Association of Urology (EAU) Guidelines on Neuro-Urology","volume":"69","author":"Groen","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1007\/s00345-018-2367-7","article-title":"Early urological care of patients with spinal cord injury","volume":"36","author":"Welk","year":"2018","journal-title":"World J. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s12325-013-0054-z","article-title":"OnabotulinumtoxinA is effective in patients with urinary incontinence due to neurogenic detrusor overactivity [corrected] regardless of concomitant anticholinergic use or neurologic etiology","volume":"30","author":"Ginsberg","year":"2013","journal-title":"Adv. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Costachescu, B., Niculescu, A.G., Dabija, M.G., Teleanu, R.I., Grumezescu, A.M., and Eva, L. (2022). Novel Strategies for Spinal Cord Regeneration. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094552"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1177\/1545968320962498","article-title":"Mental Imagery as a Rehabilitative Therapy for Neuropathic Pain in People With Spinal Cord Injury: A Randomized Controlled Trial","volume":"34","author":"Kaur","year":"2020","journal-title":"Neurorehabilit. Neural Repair"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"182","DOI":"10.3389\/fpsyt.2014.00182","article-title":"Experimental single-session imagery rescripting of distressing memories in bowel\/bladder-control anxiety: A case series","volume":"5","author":"Pajak","year":"2014","journal-title":"Front. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1111\/j.1582-4934.2011.01410.x","article-title":"Altered distribution of interstitial cells and innervation in the rat urinary bladder following spinal cord injury","volume":"16","author":"Johnston","year":"2012","journal-title":"J. Cell. Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"F966","DOI":"10.1152\/ajprenal.00359.2002","article-title":"Disruption of bladder epithelium barrier function after spinal cord injury","volume":"284","author":"Apodaca","year":"2003","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1111\/j.1464-410X.2003.04722.x","article-title":"Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment","volume":"93","author":"Brady","year":"2004","journal-title":"BJU Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.juro.2009.02.110","article-title":"Intraurethral stimulation evokes bladder responses via 2 distinct reflex pathways","volume":"182","author":"Woock","year":"2009","journal-title":"J. Urol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1088\/1741-2560\/5\/2\/005","article-title":"Improved bladder emptying in urinary retention by electrical stimulation of pudendal afferents","volume":"5","author":"Peng","year":"2008","journal-title":"J. Neural Eng."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/nau.1014","article-title":"Bladder response to urethral flow in the awake ewe","volume":"20","author":"Robain","year":"2001","journal-title":"Neurourol. Urodyn."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s00345-003-0340-5","article-title":"Role of positive urethrovesical feedback in vesical evacuation. The concept of a second micturition reflex: The urethrovesical reflex","volume":"21","author":"Shafik","year":"2003","journal-title":"World J. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1002\/nau.23590","article-title":"Evidence for an urethro-vesical crosstalk mediated by serotonin","volume":"37","author":"Coelho","year":"2018","journal-title":"Neurourol. Urodyn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/apha.12919","article-title":"Serotonergic paraneurones in the female mouse urethral epithelium and their potential role in peripheral sensory information processing","volume":"222","author":"Kullmann","year":"2018","journal-title":"Acta Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1080\/08990229970429","article-title":"Alterations in growth-associated protein (GAP-43) expression in lower urinary tract pathways following chronic spinal cord injury","volume":"16","author":"Vizzard","year":"1999","journal-title":"Somatosens. Mot. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1002\/nau.24032","article-title":"Effects of early intravesical administration of resiniferatoxin to spinal cord-injured rats in neurogenic detrusor overactivity","volume":"38","author":"Oliveira","year":"2019","journal-title":"Neurourol. Urodyn."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"F85","DOI":"10.1152\/ajprenal.00592.2016","article-title":"Urothelial proliferation and regeneration after spinal cord injury","volume":"313","author":"Kullmann","year":"2017","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1007\/s10439-008-9525-9","article-title":"The effects of long-term spinal cord injury on mechanical properties of the rat urinary bladder","volume":"36","author":"Toosi","year":"2008","journal-title":"Ann. Biomed. Eng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1016\/S0022-5347(01)62606-5","article-title":"Molecular analysis of collagens in bladder fibrosis","volume":"160","author":"Deveaud","year":"1998","journal-title":"J. Urol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/ar.23937","article-title":"Innervation of the Epithelium and Lamina Propria of the Urethra of the Female Rat","volume":"302","author":"Eggermont","year":"2019","journal-title":"Anat. Rec."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S0306-4522(01)00496-1","article-title":"Vanilloid receptor 1 expression in the rat urinary tract","volume":"109","author":"Avelino","year":"2002","journal-title":"Neuroscience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1523\/JNEUROSCI.0373-14.2015","article-title":"The Role of Brain-Derived Neurotrophic Factor (BDNF) in the Development of Neurogenic Detrusor Overactivity (NDO)","volume":"35","author":"Frias","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.expneurol.2007.01.011","article-title":"Sprouting of CGRP primary afferents in lumbosacral spinal cord precedes emergence of bladder activity after spinal injury","volume":"204","author":"Zinck","year":"2007","journal-title":"Exp. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"F796","DOI":"10.1152\/ajprenal.00097.2017","article-title":"The role of capsaicin-sensitive C-fiber afferent pathways in the control of micturition in spinal-intact and spinal cord-injured mice","volume":"313","author":"Kadekawa","year":"2017","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_35","first-page":"S3","article-title":"Neurophysiology of lower urinary tract function and dysfunction","volume":"5","author":"Yoshimura","year":"2003","journal-title":"Rev. Urol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/BF02364090","article-title":"Trophic effect of the sympathetic nervous system on vascular smooth muscle","volume":"11","author":"Fronek","year":"1983","journal-title":"Ann. Biomed. Eng."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1161\/hh2101.098379","article-title":"Trophic effect of norepinephrine on arterial intima-media and adventitia is augmented by injury and mediated by different \u03b11-adrenoceptor subtypes","volume":"89","author":"Zhang","year":"2001","journal-title":"Circ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/(SICI)1097-4652(200006)183:3<289::AID-JCP1>3.0.CO;2-6","article-title":"Stretch-activated signaling of nerve growth factor secretion in bladder and vascular smooth muscle cells from hypertensive and hyperactive rats","volume":"183","author":"Clemow","year":"2000","journal-title":"J. Cell Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1016\/S0022-5347(01)64918-8","article-title":"Regulation of nerve growth factor secretion in smooth muscle cells cultured from rat bladder body, base and urethra","volume":"157","author":"Persson","year":"1997","journal-title":"J. Urol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/nau.22438","article-title":"Neurotrophins in bladder function: What do we know and where do we go from here?","volume":"33","author":"Cruz","year":"2014","journal-title":"Neurourol. Urodyn."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"27986","DOI":"10.1074\/jbc.M312237200","article-title":"Nerve growth factor promotes the survival of sympathetic neurons through the cooperative function of the protein kinase C and phosphatidylinositol 3-kinase pathways","volume":"279","author":"Pierchala","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_42","first-page":"327","article-title":"Neural control of the lower urinary tract","volume":"5","author":"Griffiths","year":"2015","journal-title":"Compr. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.brainres.2006.12.042","article-title":"Transient suppression of the vesicular acetylcholine transporter in urinary bladder pathways following spinal cord injury","volume":"1137","author":"Takahara","year":"2007","journal-title":"Brain Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/S0166-2236(96)10072-2","article-title":"GAP-43: An intrinsic determinant of neuronal development and plasticity","volume":"20","author":"Benowitz","year":"1997","journal-title":"Trends Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1002\/nau.23539","article-title":"The effect of neutralization of nerve growth factor (NGF) on bladder and urethral dysfunction in mice with spinal cord injury","volume":"37","author":"Wada","year":"2018","journal-title":"Neurourol. Urodyn."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15951\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:42Z","timestamp":1760146902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,15]]},"references-count":45,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415951"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415951","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,12,15]]}}}