Morphofunctional Characteristics of The Urinary Bladder at Different Stages of Spinal Cord Injury: A Literature Review

Abstract

Background. Surgical Neurogenic lower urinary tract dysfunction is one of the most frequent and clinically consequential complications of spinal cord injury (SCI), affecting the great majority of patients and constituting a leading cause of morbidity, repeated hospitalisation and, historically, mortality. The urinary bladder does not respond to SCI in a static manner; rather, it undergoes a dynamic, time-dependent sequence of neurogenic remodelling whose morphological and functional characteristics differ markedly between the acute, subacute and chronic phases of injury.

Objective. To synthesise the current evidence on the stage-dependent morphofunctional characteristics of the urinary bladder after SCI, integrating neurophysiological, urodynamic, histological and molecular data, and to define the structural correlates of the principal clinical phenotypes.

Methods. A narrative literature review was conducted in PubMed, Scopus and Web of Science for articles published predominantly within the last decade (2015–2025), complemented by seminal earlier studies. Fifty-four sources describing human cohorts and experimental (rodent, minipig) SCI models were analysed and organised by injury stage, lesion level, and level of biological organisation.

Results. The evidence describes a reproducible trajectory: an acute areflexic, urine-retaining bladder during spinal shock; a subacute emergence of neurogenic detrusor overactivity (NDO) and detrusor–sphincter dyssynergia (DSD) driven by nerve growth factor–dependent C-fibre afferent sprouting; and a chronic phase dominated by detrusor hypertrophy, extracellular-matrix accumulation, a collagen type III→I shift, elastin loss and fibrosis. Quantitative data document early rapid increases in bladder mass, a biphasic course of wall compliance, an approximately 75% increase in wall thickness in chronic models, and consistent remodelling of afferent neurons. The most dangerous phenotype is the chronic suprasacral high-pressure, low-compliance bladder with DSD, which threatens the upper urinary tract, whereas sacral/infrasacral lesions more often yield an acontractile retention bladder.

Conclusion. The neurogenic bladder after SCI is best understood as a staged morphofunctional continuum. Structural findings must be interpreted together with urodynamics, because wall thickening alone does not indicate preserved function. Recognising the stage- and level-specific structural correlates is essential for timely, upper-tract-protective management and for the design of morphofunctional research.

Keywords:

Spinal cord injury, neurogenic bladder, detrusor overactivity, detrusor–sphincter dyssynergia

References

Lu Y, Shang Z, Zhang W, Pang M, Hu X, Dai Y, et al. Global incidence and characteristics of spinal cord injury since 2000–2021: a systematic review and meta-analysis. BMC Med. 2024;22(1):285.

GBD 2019 Spinal Cord Injuries Collaborators. Global, regional, and national burden of spinal cord injury, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2023;22(11):1026–1047.

Ding W, Hu S, Wang P, Kang H, Peng R, Dong Y, et al. Spinal cord injury: the global incidence, prevalence, and disability from the Global Burden of Disease Study 2019. Spine (Phila Pa 1976). 2022;47(21):1532–1540.

Kang Y, Ding H, Zhou H, Wei Z, Liu L, Pan D, et al. Epidemiology of worldwide spinal cord injury: a literature review. J Neurorestoratol. 2018;6:1–9.

Hamid R, Averbeck MA, Chiang H, Garcia A, Mousa RAT, Oh SJ, et al. Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury. World J Urol. 2018;36(10):1517–1527.

Al Taweel W, Seyam R. Neurogenic bladder in spinal cord injury patients. Res Rep Urol. 2015;7:85–99.

Fowler CJ, Griffiths D, de Groat WC. The neural control of micturition. Nat Rev Neurosci. 2008;9(6):453–466.

Panicker JN, Fowler CJ, Kessler TM. Lower urinary tract dysfunction in the neurological patient: clinical assessment and management. Lancet Neurol. 2015;14(7):720–732.

de Groat WC, Yoshimura N. Plasticity in reflex pathways to the lower urinary tract following spinal cord injury. Exp Neurol. 2012;235(1):123–132.

Shimizu N, Saito T, Wada N, Hashimoto M, Shimizu T, Kwon J, et al. Molecular mechanisms of neurogenic lower urinary tract dysfunction after spinal cord injury. Int J Mol Sci. 2023;24(9):7885.

Wada N, Karnup S, Kadekawa K, Shimizu N, Kwon J, Shimizu T, et al. Current knowledge and novel frontiers in lower urinary tract dysfunction after spinal cord injury: basic research perspectives. Urol Sci. 2022;33(3):101–113.

Kozomara M, Birkhäuser V, Anderson CE, Bywater M, Gross O, Kiss S, et al. Neurogenic lower urinary tract dysfunction in the first year after spinal cord injury: a descriptive study of urodynamic findings. J Urol. 2023;209(1):225–232.

Kim O, An L, Lee BC. Urodynamic evaluation of neurogenic bladder in patients with spinal cord injury within 6 months post-injury: a retrospective cross-sectional study. Spinal Cord. 2025;63(5):246–251.

Hogg FRA, Kearney S, Solomon E, Gallagher MJ, Zoumprouli A, Papadopoulos MC, et al. Acute, severe traumatic spinal cord injury: improving urinary bladder function by optimizing spinal cord perfusion. J Neurosurg Spine. 2021;35(6):1–8.

Mimata H, Satoh F, Tanigawa T, Nomura Y, Ogata J. Changes of rat urinary bladder during the acute phase of spinal cord injury. Urol Int. 1993;51(2):89–93.

Herrera JJ, Haywood-Watson RJ 2nd, Grill RJ. Acute and chronic deficits in the urinary bladder after spinal contusion injury in the adult rat. J Neurotrauma. 2010;27(2):423–431.

Sartori AM, Hofer AS, Scheuber MI, Rust R, Kessler TM, Schwab ME. Slow development of bladder malfunction parallels spinal cord fiber sprouting and interneurons' loss after spinal cord transection. Exp Neurol. 2021;348:113937.

Breyer BN, Fandel TM, Alwaal A, Osterberg EC, Shindel AW, Lin G, et al. Comparison of spinal cord contusion and transection: functional and histological changes in the rat urinary bladder. BJU Int. 2017;119(2):333–341.

Foditsch EE, Roider K, Patras I, Huțu I, Bauer S, Janetschek G, et al. Structural changes of the urinary bladder after chronic complete spinal cord injury in minipigs. Int Neurourol J. 2017;21(1):12–19.

Bushnell J, Cates LN, Hyde J, Hofstetter CP, Yang CC, Khaing ZZ. Early detrusor application of botulinum toxin A results in reduced bladder hypertrophy and fibrosis after spinal cord injury in a rodent model. Toxins. 2022;14(11):777.

Tuttle TG, Lujan HL, Tykocki NR, DiCarlo SE, Roccabianca S. Remodeling of extracellular matrix in the urinary bladder of paraplegic rats results in increased compliance and delayed fiber recruitment 16 weeks after spinal cord injury. Acta Biomater. 2022;141:280–289.

Von Siebenthal M, Akshay A, Besic M, Schneider MP, Gheinani AH, Burkhard FC, et al. Molecular characterization of non-neurogenic and neurogenic lower urinary tract dysfunction in SCI-induced and partial bladder outlet obstruction mouse models. Int J Mol Sci. 2023;24(3):2451.

Bai K, Hou Y, Zhang Z, Yuan F, Huang X, Liu P, et al. A new rat model of sacral cord injury producing a neurogenic bladder and its functional and mechanistic studies. Biomolecules. 2024;14(9):1141.

Ferreira A, Chambel SS, Avelino A, Cruz CD. Spinal cord injury causes marked tissue rearrangement in the urethra—an experimental study in the rat. Int J Mol Sci. 2022;23(24):15951.

Ferreira A, Chambel SS, Avelino A, Nascimento D, Silva N, Duarte Cruz C. Urinary dysfunction after spinal cord injury: comparing outcomes after thoracic spinal transection and contusion in the rat. Neuroscience. 2024;554:70–81.

Li J, Huang J, Chen L, Ren W, Cai W. Human umbilical cord mesenchymal stem cells contribute to the reconstruction of bladder function after acute spinal cord injury via the p38 MAPK/NF-κB pathway. Bioengineered. 2022;13(2):4844–4856.

Yoshimura N, de Groat WC. Effects of spinal cord injury on neurofilament immunoreactivity and capsaicin sensitivity in rat dorsal root ganglion neurons innervating the urinary bladder. Neuroscience. 1998;83(2):633–643.

Zvara P, Vizzard MA. Exogenous overexpression of nerve growth factor in the urinary bladder produces bladder overactivity and altered micturition circuitry in the lumbosacral spinal cord. BMC Physiol. 2007;7:9.

Chambel SS, Ferreira A, Oliveira R, Miranda R, Vale L, Reguenga C, et al. 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. 2022;23(15):8667.

Seki S, Sasaki K, Fraser MO, Igawa Y, Nishizawa O, Chancellor MB, et al. Immunoneutralization of nerve growth factor in lumbosacral spinal cord reduces bladder hyperreflexia in spinal cord injured rats. J Urol. 2002;168(5):2269–2274.

Seki S, Sasaki K, Igawa Y, Nishizawa O, Chancellor MB, de Groat WC, et al. Suppression of detrusor–sphincter dyssynergia by immunoneutralization of nerve growth factor in lumbosacral spinal cord in spinal cord injured rats. J Urol. 2004;171(1):478–482.

Ochodnicky P, Cruz CD, Yoshimura N, Cruz F. Neurotrophins as regulators of urinary bladder function. Nat Rev Urol. 2012;9(11):628–637.

Cruz CD. Neurotrophins in bladder function: what do we know and where do we go from here? Neurourol Urodyn. 2014;33(1):39–45.

Fry CH, Kitney DG, Paniker J, Drake MJ, Kanai A, Andersson KE. Fibrosis and the bladder, implications for function. ICI-RS 2017. Neurourol Urodyn. 2018;37(S4):S7–S12.

Johnston L, Cunningham RM, Young JS, Fry CH, McMurray G, Eccles R, et al. Altered distribution of interstitial cells and innervation in the rat urinary bladder following spinal cord injury. J Cell Mol Med. 2012;16(7):1533–1543.

Toosi KK, Nagatomi J, Chancellor MB, Sacks MS. The effects of long-term spinal cord injury on the mechanical properties of the rat urinary bladder. Ann Biomed Eng. 2008;36(9):1470–1480.

Zhao M, Ding N, Wang H, Zu S, Liu H, Wen J, et al. Activation of TRPA1 in bladder suburothelial myofibroblasts counteracts TGF-β1-induced fibrotic changes. Int J Mol Sci. 2023;24(11):9501.

Chen J, Li Q, Hong Y, Zhou X, Yu C, Tian X, et al. Inhibition of the NF-κB signaling pathway alleviates pyroptosis in bladder epithelial cells and neurogenic bladder fibrosis. Int J Mol Sci. 2023;24(13):11160.

Yang X, Pu Q, Wen Y, Zhao Y, Wang J, Xu P, et al. Activation of the TGF-β1/Smads/α-SMA pathway is related to histological and functional changes in children with neurogenic bladder. Sci Rep. 2022;12:9631.

Steadman CJ, Grill WM. Spinal cord stimulation for the restoration of bladder function after spinal cord injury. Healthc Technol Lett. 2020;7(3):87–92.

Chen SF, Jiang YH, Jhang JF, Kuo HC. Satisfaction with detrusor onabotulinumtoxinA injections and conversion to other bladder management in patients with chronic spinal cord injury. Toxins. 2022;14(1):35.

Cameron AP, Wallner LP, Tate DG, Sarma AV, Rodriguez GM, Clemens JQ. Bladder management after spinal cord injury in the United States 1972 to 2005. J Urol. 2010;184(1):213–217.

Weld KJ, Dmochowski RR. Effect of bladder management on urological complications in spinal cord injured patients. J Urol. 2000;163(3):768–772.

Gerridzen RG, Thijssen AM, Dehoux E. Risk factors for upper tract deterioration in chronic spinal cord injury patients. J Urol. 1992;147(2):416–418.

McGuire EJ, Woodside JR, Borden TA, Weiss RM. Prognostic value of urodynamic testing in myelodysplastic patients. J Urol. 1981;126(2):205–209.

Ruffion A, Castro-Díaz D, Patel H, Khalaf K, Onyenwenyi A, Globe D, et al. Systematic review of the epidemiology of urinary incontinence and detrusor overactivity among patients with neurogenic overactive bladder. Neuroepidemiology. 2013;41(3-4):146–155.

Wyndaele JJ. The management of neurogenic lower urinary tract dysfunction after spinal cord injury. Nat Rev Urol. 2016;13(12):705–714.

Manack A, Motsko SP, Haag-Molkenteller C, Ruggieri M, Chancellor MB, Sahai A, et al. Epidemiology and healthcare utilization of neurogenic bladder patients in a US claims database. Neurourol Urodyn. 2011;30(3):395–401.

Kaplan SA, Chancellor MB, Blaivas JG. Bladder and sphincter behavior in patients with spinal cord lesions. J Urol. 1991;146(1):113–117.

Groen J, Pannek J, Castro Diaz D, Del Popolo G, Gross T, Hamid R, et al. Summary of European Association of Urology (EAU) guidelines on neuro-urology. Eur Urol. 2016;69(2):324–333.

Drake MJ, Apostolidis A, Cocci A, Emmanuel A, Gajewski JB, Harrison SCW, et al. Neurogenic lower urinary tract dysfunction: clinical management recommendations of the Neurologic Incontinence Committee of the Fifth International Consultation on Incontinence 2013. Neurourol Urodyn. 2016;35(6):657–665.

Vizzard MA. Neurochemical plasticity and the role of neurotrophic factors in bladder reflex pathways after spinal cord injury. Prog Brain Res. 2006;152:97–115.

Kadekawa K, Yoshimura N, Majima T, Wada N, Shimizu T, Birder LA, et al. Characterization of bladder and external urethral activity in mice with or without spinal cord injury—a comparison study with rats. Am J Physiol Regul Integr Comp Physiol. 2016;310(8):R752–R758.

Andersson KE, Wein AJ. Pharmacology of the lower urinary tract: basis for current and future treatments of urinary incontinence. Pharmacol Rev. 2004;56(4):581–631.