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Effect of Gender on Recovery After Spinal Cord Injury

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Abstract

Spinal cord injury (SCI) is a debilitating condition that affects thousands of new individuals each year, the majority of which are males. Males with SCI tend to be injured at an earlier age, mostly during sports or motor vehicle accidents, whereas females tend be injured later in life, particularly in the age group 65 and older. In both experimental and clinical studies, the question as to whether gender affects outcome has been addressed in a variety of patient groups and animal models. Results from experimental paradigms have suggested that a gender bias in outcome exists that favors females and appears to involve the advantageous or disadvantageous effects of the gonadal sex hormones estrogen and progesterone or testosterone, respectively. However, other studies have shown an absence of gender differences in outcome in specific SCI models and work has also questioned the involvement of female sex hormones in the observed outcome improvements in females. Similar controversy exists clinically, in studies that have examined gender disparities in outcome after SCI. The current review examines the experimental and clinical evidence for a gender bias in outcome following SCI and discusses issues that have made it difficult to conclusively answer this question.

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References

  1. David S, Lopez-Vales R, Wee Yong V. Harmful and beneficial effects of inflammation after spinal cord injury: potential therapeutic implications. Handbook of clinical neurology, edited by PJ Vinken and GW Bruyn. Amsterdam: Elsevier B.V.; 2012;109:485–502. doi:10.1016/B978-0-444-52137-8.00030-9.

  2. Zhang N, Yin Y, Xu SJ, Wu YP, Chen WS. Inflammation and apoptosis in spinal cord injury. Indian J Med Res. 2012;135(3):287.

    PubMed  CAS  Google Scholar 

  3. Becker D, Sadowsky CL, McDonald JW. Restoring function after spinal cord injury. Neurologist. 2003;9(1):1–15. doi:10.1097/01.nrl.0000038587.58012.05.

    Article  PubMed  Google Scholar 

  4. Liu NK, Zhang YP, Titsworth WL, Jiang X, Han S, Lu PH, et al. A novel role of phospholipase A2 in mediating spinal cord secondary injury. Ann Neurol. 2006;59(4):606–19. doi:10.1002/ana.20798.

    Article  PubMed  CAS  Google Scholar 

  5. Maynard Jr FM, Bracken MB, Creasey G, Ditunno Jr JF, Donovan WH, Ducker TB, et al. International standards for neurological and functional classification of spinal cord injury. American Spinal Injury Association. Spinal Cord. 1997;35(5):266–74.

    Article  PubMed  Google Scholar 

  6. Sekhon LH, Fehlings MG. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine. 2001;26(24 Suppl):S2–12.

    Article  PubMed  CAS  Google Scholar 

  7. Devivo MJ. Epidemiology of traumatic spinal cord injury: trends and future implications. Spinal Cord. 2012;50(5):365–72. doi:10.1038/sc.2011.178.

    Article  PubMed  CAS  Google Scholar 

  8. Nobunaga AI, Go BK, Karunas RB. Recent demographic and injury trends in people served by the Model Spinal Cord Injury Care Systems. Arch Phys Med Rehabil. 1999;80(11):1372–82.

    Article  PubMed  CAS  Google Scholar 

  9. Furlan JC, Krassioukov AV, Fehlings MG. The effects of gender on clinical and neurological outcomes after acute cervical spinal cord injury. J Neurotrauma. 2005;22(3):368–81. doi:10.1089/neu.2005.22.368.

    Article  PubMed  Google Scholar 

  10. Sipski ML, Jackson AB, Gomez-Marin O, Estores I, Stein A. Effects of gender on neurologic and functional recovery after spinal cord injury. Arch Phys Med Rehabil. 2004;85(11):1826–36.

    Article  PubMed  Google Scholar 

  11. Hauben E, Mizrahi T, Agranov E, Schwartz M. Sexual dimorphism in the spontaneous recovery from spinal cord injury: a gender gap in beneficial autoimmunity? Eur J Neurosci. 2002;16(9):1731–40.

    Article  PubMed  Google Scholar 

  12. Farooque M, Suo Z, Arnold PM, Wulser MJ, Chou CT, Vancura RW, et al. Gender-related differences in recovery of locomotor function after spinal cord injury in mice. Spinal Cord. 2006;44(3):182–7. doi:10.1038/sj.sc.3101816.

    Article  PubMed  CAS  Google Scholar 

  13. Greenwald BD, Seel RT, Cifu DX, Shah AN. Gender-related differences in acute rehabilitation lengths of stay, charges, and functional outcomes for a matched sample with spinal cord injury: a multicenter investigation. Arch Phys Med Rehabil. 2001;82(9):1181–7. doi:10.1053/apmr.2001.24891.

    Article  PubMed  CAS  Google Scholar 

  14. Samantaray S, Smith JA, Das A, Matzelle DD, Varma AK, Ray SK, et al. Low dose estrogen prevents neuronal degeneration and microglial reactivity in an acute model of spinal cord injury: effect of dosing, route of administration, and therapy delay. Neurochem Res. 2011;36(10):1809–16. doi:10.1007/s11064-011-0498-y.

    Article  PubMed  CAS  Google Scholar 

  15. Borowicz KK, Piskorska B, Banach M, Czuczwar SJ. Neuroprotective actions of neurosteroids. Front Endocrinol. 2011;2:50. doi:10.3389/fendo.2011.00050.

    Article  Google Scholar 

  16. Bramlett HM, Dietrich WD. Neuropathological protection after traumatic brain injury in intact female rats versus males or ovariectomized females. J Neurotrauma. 2001;18(9):891–900. doi:10.1089/089771501750451811.

    Article  PubMed  CAS  Google Scholar 

  17. Roof RL, Hall ED. Estrogen-related gender difference in survival rate and cortical blood flow after impact-acceleration head injury in rats. J Neurotrauma. 2000;17(12):1155–69.

    Article  PubMed  CAS  Google Scholar 

  18. Anderson KD, Sharp KG, Steward O. Bilateral cervical contusion spinal cord injury in rats. Exp Neurol. 2009;220(1):9–22. doi:10.1016/j.expneurol.2009.06.012.

    Article  PubMed  Google Scholar 

  19. Gensel JC, Tovar CA, Hamers FP, Deibert RJ, Beattie MS, Bresnahan JC. Behavioral and histological characterization of unilateral cervical spinal cord contusion injury in rats. J Neurotrauma. 2006;23(1):36–54. doi:10.1089/neu.2006.23.36.

    Article  PubMed  Google Scholar 

  20. Ung RV, Lapointe NP, Tremblay C, Larouche A, Guertin PA. Spontaneous recovery of hindlimb movement in completely spinal cord transected mice: a comparison of assessment methods and conditions. Spinal Cord. 2007;45(5):367–79. doi:10.1038/sj.sc.3101970.

    PubMed  CAS  Google Scholar 

  21. Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995;12(1):1–21.

    Article  PubMed  CAS  Google Scholar 

  22. Fowler SC, Birkestrand BR, Chen R, Moss SJ, Vorontsova E, Wang G, et al. A force-plate actometer for quantitating rodent behaviors: illustrative data on locomotion, rotation, spatial patterning, stereotypies, and tremor. J Neurosci Meth. 2001;107(1–2):107–24.

    Article  CAS  Google Scholar 

  23. Hall ED, Gibson TR, Pavel KM. Lack of a gender difference in post-traumatic neurodegeneration in the mouse controlled cortical impact injury model. J Neurotrauma. 2005;22(6):669–79. doi:10.1089/neu.2005.22.669.

    Article  PubMed  Google Scholar 

  24. Lahita RG. Effects of gender on the immune system. Implications for neuropsychiatric systemic lupus erythematosus. Ann N Y Acad Sci. 1997;823:247–51.

    Article  PubMed  CAS  Google Scholar 

  25. Whitacre CC, Reingold SC, O'Looney PA. A gender gap in autoimmunity. Science. 1999;283(5406):1277–8.

    Article  PubMed  CAS  Google Scholar 

  26. Angele MK, Ayala A, Cioffi WG, Bland KI, Chaudry IH. Testosterone: the culprit for producing splenocyte immune depression after trauma hemorrhage. Am J Physiol. 1998;274(6 Pt 1):C1530–6.

    PubMed  CAS  Google Scholar 

  27. Angele MK, Schwacha MG, Ayala A, Chaudry IH. Effect of gender and sex hormones on immune responses following shock. Shock. 2000;14(2):81–90.

    Article  PubMed  CAS  Google Scholar 

  28. Birk K, Ford C, Smeltzer S, Ryan D, Miller R, Rudick RA. The clinical course of multiple sclerosis during pregnancy and the puerperium. Arch Neurol. 1990;47(7):738–42.

    Article  PubMed  CAS  Google Scholar 

  29. Offner H, Adlard K, Zamora A, Vandenbark AA. Estrogen potentiates treatment with T-cell receptor protein of female mice with experimental encephalomyelitis. J Clin Investig. 2000;105(10):1465–72. doi:10.1172/JCI9213.

    Article  PubMed  CAS  Google Scholar 

  30. Bebo Jr BF, Fyfe-Johnson A, Adlard K, Beam AG, Vandenbark AA, Offner H. Low-dose estrogen therapy ameliorates experimental autoimmune encephalomyelitis in two different inbred mouse strains. J Immunol. 2001;166(3):2080–9.

    PubMed  CAS  Google Scholar 

  31. Weinstein Y, Ran S, Segal S. Sex-associated differences in the regulation of immune responses controlled by the MHC of the mouse. J Immunol. 1984;132(2):656–61.

    PubMed  CAS  Google Scholar 

  32. Dalal M, Kim S, Voskuhl RR. Testosterone therapy ameliorates experimental autoimmune encephalomyelitis and induces a T helper 2 bias in the autoantigen-specific T lymphocyte response. J Immunol. 1997;159(1):3–6.

    PubMed  CAS  Google Scholar 

  33. Bebo Jr BF, Zelinka-Vincent E, Adamus G, Amundson D, Vandenbark AA, Offner H. Gonadal hormones influence the immune response to PLP 139-151 and the clinical course of relapsing experimental autoimmune encephalomyelitis. J Neuroimmunol. 1998;84(2):122–30.

    Article  PubMed  CAS  Google Scholar 

  34. Benten WP, Lieberherr M, Giese G, Wrehlke C, Stamm O, Sekeris CE, et al. Functional testosterone receptors in plasma membranes of T cells. FASEB J. 1999;13(1):123–33.

    PubMed  CAS  Google Scholar 

  35. Liva SM, Voskuhl RR. Testosterone acts directly on CD4+ T lymphocytes to increase IL-10 production. J Immunol. 2001;167(4):2060–7.

    PubMed  CAS  Google Scholar 

  36. Calzolari A. Recherches experimentales surun rapport probable entre la fonction du thymus et cells des testiclulis. Arch Ital Biol. 1898;30:71–89.

    Google Scholar 

  37. Moalem G, Monsonego A, Shani Y, Cohen IR, Schwartz M. Differential T cell response in central and peripheral nerve injury: connection with immune privilege. FASEB J. 1999;13(10):1207–17.

    PubMed  CAS  Google Scholar 

  38. Hauben E, Butovsky O, Nevo U, Yoles E, Moalem G, Agranov E, et al. Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. J Neurosci. 2000;20(17):6421–30.

    PubMed  CAS  Google Scholar 

  39. Hauben E, Nevo U, Yoles E, Moalem G, Agranov E, Mor F, et al. Autoimmune T cells as potential neuroprotective therapy for spinal cord injury. Lancet. 2000;355(9200):286–7.

    Article  PubMed  CAS  Google Scholar 

  40. Thomas AJ, Nockels RP, Pan HQ, Shaffrey CI, Chopp M. Progesterone is neuroprotective after acute experimental spinal cord trauma in rats. Spine. 1999;24(20):2134–8.

    Article  PubMed  CAS  Google Scholar 

  41. Singh M, Su C. Progesterone and neuroprotection. Hormones and behavior. 2012. doi:10.1016/j.yhbeh.2012.06.003.

  42. De Nicola AF, Labombarda F, Deniselle MC, Gonzalez SL, Garay L, Meyer M, et al. Progesterone neuroprotection in traumatic CNS injury and motoneuron degeneration. Front Neuroendocrinol. 2009;30(2):173–87. doi:10.1016/j.yfrne.2009.03.001.

    Article  PubMed  Google Scholar 

  43. De Nicola AF, Gonzalez SL, Labombarda F, Deniselle MC, Garay L, Guennoun R, et al. Progesterone treatment of spinal cord injury: effects on receptors, neurotrophins, and myelination. J Mol Neurosci. 2006;28(1):3–15. doi:10.1385/JMN:30:3:341.

    Article  PubMed  Google Scholar 

  44. Swartz KR, Fee DB, Joy KM, Roberts KN, Sun S, Scheff NN, et al. Gender differences in spinal cord injury are not estrogen-dependent. J Neurotrauma. 2007;24(3):473–80. doi:10.1089/neu.2006.0167.

    Article  PubMed  Google Scholar 

  45. Fee DB, Swartz KR, Joy KM, Roberts KN, Scheff NN, Scheff SW. Effects of progesterone on experimental spinal cord injury. Brain Res. 2007;1137(1):146–52. doi:10.1016/j.brainres.2006.12.024.

    Article  PubMed  CAS  Google Scholar 

  46. Gilmer LK, Roberts KN, Scheff SW. Efficacy of progesterone following a moderate unilateral cortical contusion injury. J Neurotrauma. 2008;25(6):593–602. doi:10.1089/neu.2007.0477.

    Article  PubMed  Google Scholar 

  47. Kay E, Deutsch A, Chen D, Semik P, Rowles D. Effects of gender on inpatient rehabilitation outcomes in the elderly with incomplete paraplegia from nontraumatic spinal cord injury. J Spinal Cord Med. 2010;33(4):379–86.

    PubMed  Google Scholar 

  48. Lynch AC, Wong C, Anthony A, Dobbs BR, Frizelle FA. Bowel dysfunction following spinal cord injury: a description of bowel function in a spinal cord-injured population and comparison with age and gender matched controls. Spinal Cord. 2000;38(12):717–23.

    Article  PubMed  CAS  Google Scholar 

  49. Kirshblum S, Johnston MV, Brown J, O'Connor KC, Jarosz P. Predictors of dysphagia after spinal cord injury. Arch Phys Med Rehabil. 1999;80(9):1101–5.

    Article  PubMed  CAS  Google Scholar 

  50. Scivoletto G, Morganti B, Molinari M. Sex-related differences of rehabilitation outcomes of spinal cord lesion patients. Clin Rehabil. 2004;18(6):709–13.

    Article  PubMed  Google Scholar 

  51. Bonica J. Introduction: semantic, epidemiologic and educational issues. In: Casey KL, editor. Pain and central nervous system disease: the central pain syndromes. New York: Raven; 1991. p. 13–29.

    Google Scholar 

  52. Cardenas DD, Bryce TN, Shem K, Richards JS, Elhefni H. Gender and minority differences in the pain experience of people with spinal cord injury. Arch Phys Med Rehabil. 2004;85(11):1774–81.

    Article  PubMed  Google Scholar 

  53. Werhagen L, Budh CN, Hultling C, Molander C. Neuropathic pain after traumatic spinal cord injury—relations to gender, spinal level, completeness, and age at the time of injury. Spinal Cord. 2004;42(12):665–73. doi:10.1038/sj.sc.3101641.

    Article  PubMed  CAS  Google Scholar 

  54. Budh CN, Lund I, Hultling C, Levi R, Werhagen L, Ertzgaard P, et al. Gender related differences in pain in spinal cord injured individuals. Spinal Cord. 2003;41(2):122–8. doi:10.1038/sj.sc.3101407.

    Article  Google Scholar 

  55. Krause JS, Anson CA. Employment after spinal cord injury: relation to selected participant characteristics. Arch Phys Med Rehabil. 1996;77(8):737–43.

    Article  PubMed  CAS  Google Scholar 

  56. Hess DW, Ripley DL, McKinley WO, Tewksbury M. Predictors for return to work after spinal cord injury: a 3-year multicenter analysis. Arch Phys Med Rehabil. 2000;81(3):359–63.

    Article  PubMed  CAS  Google Scholar 

  57. Krause JS, Sternberg M, Maides J, Lottes S. Employment after spinal cord injury: differences related to geographic region, gender, and race. Arch Phys Med Rehabil. 1998;79(6):615–24.

    Article  PubMed  CAS  Google Scholar 

  58. Frank RG, Chaney JM, Clay DL, Shutty MS, Beck NC, Kay DR, et al. Dysphoria: a major symptom factor in persons with disability or chronic illness. Psychiatr Res. 1992;43(3):231–41.

    Article  CAS  Google Scholar 

  59. Kennedy P, Rogers BA. Anxiety and depression after spinal cord injury: a longitudinal analysis. Arch Phys Med Rehabil. 2000;81(7):932–7. doi:10.1053/apmr.2000.5580.

    Article  PubMed  CAS  Google Scholar 

  60. Frank RG, Kashani JH, Wonderlich SA, Lising A, Visot LR. Depression and adrenal function in spinal cord injury. Am J Psychiatry. 1985;142(2):252–3.

    PubMed  CAS  Google Scholar 

  61. Judd FK, Brown DJ. Psychiatric consultation in a spinal injuries unit. Aust New Zeal J Psychiatr. 1992;26(2):218–22.

    Article  CAS  Google Scholar 

  62. Krause JS, Kemp B, Coker J. Depression after spinal cord injury: relation to gender, ethnicity, aging, and socioeconomic indicators. Arch Phys Med Rehabil. 2000;81(8):1099–109.

    Article  PubMed  CAS  Google Scholar 

  63. Lorant V, Deliege D, Eaton W, Robert A, Philippot P, Ansseau M. Socioeconomic inequalities in depression: a meta-analysis. Am J Epidemiol. 2003;157(2):98–112.

    Article  PubMed  CAS  Google Scholar 

  64. Klepac N, Trkulja V. Education effect on depression and quality of life in nondemented Parkinson’s disease patients. J Neuropsychiatry Clin Neurosci. 2009;21(3):314–22.

    Google Scholar 

  65. Krause JS, Broderick L. Outcomes after spinal cord injury: comparisons as a function of gender and race and ethnicity. Arch Phys Med Rehabil. 2004;85(3):355–62.

    Article  PubMed  Google Scholar 

  66. Hatchett PE, Requejo PS, Mulroy SJ, Haubert LL, Eberly VJ, Conners SG. Impact of gender on shoulder torque and manual wheelchair usage for individuals with paraplegia: a preliminary report. Top Spinal Cord Inj Rehabil. 2009;15(2):79–89. doi:10.1310/sci1502-79.

    Article  PubMed  Google Scholar 

  67. Jang HJ, Park J, Shin HI. Length of hospital stay in patients with spinal cord injury. Ann Rehabil Med. 2011;35(6):798–806. doi:10.5535/arm.2011.35.6.798.

    Article  PubMed  Google Scholar 

  68. Franke AC, Snoek GJ, de Groot S, Nene AV, Spooren AI, Post MW. Arm hand skilled performance in persons with a cervical spinal cord injury-long-term follow-up. Spinal cord. 2012. doi:10.1038/sc.2012.95.

  69. Harrop JS, Naroji S, Maltenfort MG, Ratliff JK, Tjoumakaris SI, Frank B, et al. Neurologic improvement after thoracic, thoracolumbar, and lumbar spinal cord (conus medullaris) injuries. Spine. 2011;36(1):21–5. doi:10.1097/BRS.0b013e3181fd6b36.

    Article  PubMed  Google Scholar 

  70. Krause JS. Dimensions of subjective well-being after spinal cord injury: an empirical analysis by gender and race/ethnicity. Arch Phys Med Rehabil. 1998;79(8):900–9.

    Article  PubMed  CAS  Google Scholar 

  71. Chien LC, Wu JC, Chen YC, Liu L, Huang WC, Chen TJ, et al. Age, sex, and socio-economic status affect the incidence of pediatric spinal cord injury: an eleven-year national cohort study. PLoS One. 2012;7(6):e39264. doi:10.1371/journal.pone.0039264.

    Article  PubMed  CAS  Google Scholar 

  72. Tsitouras PD, Zhong YG, Spungen AM, Bauman WA. Serum testosterone and growth hormone/insulin-like growth factor-I in adults with spinal cord injury. Horm Metab Res. 1995;27(6):287–92. doi:10.1055/s-2007-979961.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Damien D. Pearse.

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Isabel Lee is a visiting summer research student from Kalamazoo College, Kalamazoo, MI 49006, USA.

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Chan, WM., Mohammed, Y., Lee, I. et al. Effect of Gender on Recovery After Spinal Cord Injury. Transl. Stroke Res. 4, 447–461 (2013). https://doi.org/10.1007/s12975-012-0249-7

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