Myelin pathogenesis and functional deficits following SCI are age-associated

Experimental Neurology

Volumn 213, Issue 2, 2008, Pages 363-371

  Siegenthaler, Monica M ^a   Ammon, Denise L ^a   Keirstead, Hans S ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Aging; Demyelination; Remyelination; Spinal cord injury

Indexed keywords

MYELIN; TOXIN;

AGING; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLADDER FUNCTION; DEMYELINATION; LOCOMOTION; NONHUMAN; PATHOGENESIS; PATHOLOGY; PRIORITY JOURNAL; RAT; REGENERATIVE ABILITY; REMYELINIZATION; SPINAL CORD INJURY;

AGE FACTORS; AGING; ANIMALS; DEMYELINATING DISEASES; FEMALE; MOTOR ACTIVITY; MYELIN SHEATH; NERVE FIBERS, MYELINATED; RATS; RATS, SPRAGUE-DAWLEY; RECOVERY OF FUNCTION; SPINAL CORD INJURIES; URINARY BLADDER DISEASES;

EID: 51549087318     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2008.06.015     Document Type: Article

References (85)

1. Arsenijevic Y., and Weiss S. Insulin-like growth factor-I is a differentiation factor for postmitotic CNS stem cell-derived neuronal precursors: distinct actions from those of brain-derived neurotrophic factor. J. Neurosci. 18 (1998) 2118-2128
2. Azcoitia I., Sierra A., Veiga S., and Garcia-Segura L.M. Aromatase expression by reactive astroglia is neuroprotective. Ann. N. Y. Acad. Sci. 1007 (2003) 298-305
3. Bartzokis G. Age-associated myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease. Neurobiol. Aging 25 (2004) 5-18 author reply 49-62
4. Basso D.M., Beattie M.S., and Bresnahan J.C. A sensitive and reliable locomotor rating scale for open field testing in rats. J. Neurotrauma. 12 (1995) 1-21
5. Blight A.R. Remyelination, revascularization, and recovery of function in experimental spinal cord injury. Adv. Neurol. 59 (1993) 91-104
6. Bunge R.P., Puckett W.R., Becerra J.L., Marcillo A., and Quencer R.M. Observations on the pathology of human spinal cord injury. A review and classification of 22 new cases with details from a case of chronic cord compression with extensive focal demyelination. Adv. Neurol. 59 (1993) 75-89
7. Chari D.M., Crang A.J., and Blakemore W.F. Decline in rate of colonization of oligodendrocyte progenitor cell (OPC)-depleted tissue by adult OPCs with age. J. Neuropathol. Exp. Neurol. 62 (2003) 908-916
8. Cheng B., and Mattson M.P. NT-3 and BDNF protect CNS neurons against metabolic/excitotoxic insults. Brain Res. 640 (1994) 56-67
9. Ciriza I., Azcoitia I., and Garcia-Segura L.M. Reduced progesterone metabolites protect rat hippocampal neurones from kainic acid excitotoxicity in vivo. J. Neuroendocrinol. 16 (2004) 58-63
10. Ciriza I., Carrero P., Azcoitia I., Lundeen S.G., and Garcia-Segura L.M. Selective estrogen receptor modulators protect hippocampal neurons from kainic acid excitotoxicity: differences with the effect of estradiol. J. Neurobiol. 61 (2004) 209-221
11. Davis M., Mendelow A.D., Perry R.H., Chambers I.R., and James O.F. Experimental stroke and neuroprotection in the aging rat brain. Stroke 26 (1995) 1072-1078
12. De Nicola A.F., Gonzalez S.L., Labombarda F., Deniselle M.C., Garay L., Guennoun R., and Schumacher M. Progesterone treatment of spinal cord injury: Effects on receptors, neurotrophins, and myelination. J. Mol. Neurosci. 28 (2006) 3-15
13. Du Y., Fischer T.Z., Lee L.N., Lercher L.D., and Dreyfus C.F. Regionally specific effects of BDNF on oligodendrocytes. Dev. Neurosci. 25 (2003) 116-126
14. Erdincler P., Tuzgen S., Erdincler U.D., Oguz E., Korpinar A., Ciplak N., and Kuday C. Influence of aging on blood-brain barrier permeability and free radical formation following experimental brain cold injury. Acta Neurochir. (Wien) 144 (2002) 195-199 discussion 199-200
15. Genazzani A.R., Petraglia F., Bernardi F., Casarosa E., Salvestroni C., Tonetti A., Nappi R.E., Luisi S., Palumbo M., Purdy R.H., and Luisi M. Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences. J. Clin. Endocrinol. Metab. 83 (1998) 2099-2103
16. Genovese T., Mazzon E., Di Paola R., Crisafulli C., Muia C., Bramanti P., and Cuzzocrea S. Increased oxidative-related mechanisms in the spinal cord injury in old rats. Neurosci. Lett. 393 (2006) 141-146
17. Ghoumari A.M., Ibanez C., El-Etr M., Leclerc P., Eychenne B., O'Malley B.W., Baulieu E.E., and Schumacher M. Progesterone and its metabolites increase myelin basic protein expression in organotypic slice cultures of rat cerebellum. J. Neurochem. 86 (2003) 848-859
18. Gilson J.M., and Blakemore W.F. Schwann cell remyelination is not replaced by oligodendrocyte remyelination following ethidium bromide induced demyelination. Neuroreport 13 (2002) 1205-1208
19. Glaser J., Gonzalez R., Perreau V.M., Cotman C.W., and Keirstead H.S. Neutralization of the chemokine CXCL10 enhances tissue sparing and angiogenesis following spinal cord injury. J. Neurosci. Res. 77 (2004) 701-708
20. Glaser J., Gonzalez R., Sadr E., and Keirstead H.S. Neutralization of the chemokine CXCL10 reduces apoptosis and increases axon sprouting after spinal cord injury. J. Neurosci. Res. 84 (2006) 724-734
21. Gong Y., Hua Y., Keep R.F., Hoff J.T., and Xi G. Intracerebral hemorrhage: effects of aging on brain edema and neurological deficits. Stroke 35 (2004) 2571-2575
22. Gonzalez R., Glaser J., Liu M.T., Lane T.E., and Keirstead H.S. Reducing inflammation decreases secondary degeneration and functional deficit after spinal cord injury. Exp. Neurol. 184 (2003) 456-463
23. Guy J., Ellis E.A., Kelley K., and Hope G.M. Spectra of G ratio, myelin sheath thickness, and axon and fiber diameter in the guinea pig optic nerve. J. Comp. Neurol. 287 (1989) 446-454
24. Gwak Y.S., Hains B.C., Johnson K.M., and Hulsebosch C.E. Effect of age at time of spinal cord injury on behavioral outcomes in rat. J. Neurotrauma. 21 (2004) 983-993
25. Hausmann O.N. Post-traumatic inflammation following spinal cord injury. Spinal. Cord. 41 (2003) 369-378
26. Hayashi M., Yamashita A., and Shimizu K. Somatostatin and brain-derived neurotrophic factor mRNA expression in the primate brain: decreased levels of mRNAs during aging. Brain. Res. 749 (1997) 283-289
27. Hildebrand C., and Hahn R. Relation between myelin sheath thickness and axon size in spinal cord white matter of some vertebrate species. J. Neurol. Sci. 38 (1978) 421-434
28. Hinks G.L., and Franklin R.J. Delayed changes in growth factor gene expression during slow remyelination in the CNS of aged rats. Mol. Cell. Neurosci. 16 (2000) 542-556
29. Hoffman A.R., Lieberman S.A., and Ceda G.P. Growth hormone therapy in the elderly: implications for the aging brain. Psychoneuroendocrinology 17 (1992) 327-333
30. Ibanez C., Shields S.A., El-Etr M., Leonelli E., Magnaghi V., Li W.W., Sim F.J., Baulieu E.E., Melcangi R.C., Schumacher M., and Franklin R.J. Steroids and the reversal of age-associated changes in myelination and remyelination. Prog. Neurobiol. 71 (2003) 49-56
31. Ibanez C., Shields S.A., El-Etr M., Baulieu E.E., Schumacher M., and Franklin R.J. Systemic progesterone administration results in a partial reversal of the age-associated decline in CNS remyelination following toxin-induced demyelination in male rats. Neuropathol. Appl. Neurobiol. 30 (2004) 80-89
32. Jeffery N.D., and Blakemore W.F. Locomotor deficits induced by experimental spinal cord demyelination are abolished by spontaneous remyelination. Brain 120 (1997) 27-37
33. Jeffery N.D., Crang A.J., O'Leary M.T., Hodge S.J., and Blakemore W.F. Behavioural consequences of oligodendrocyte progenitor cell transplantation into experimental demyelinating lesions in the rat spinal cord. Eur. J. Neurosci. 11 (1999) 1508-1514
34. Kakulas B.A. The applied neuropathology of human spinal cord injury. Spinal. Cord. 37 (1999) 79-88
35. Keirstead H.S., and Blakemore W.F. Identification of post-mitotic oligodendrocytes incapable of remyelination within the demyelinated adult spinal cord. J. Neuropathol. Exp. Neurol. 56 (1997) 1191-1201
36. Keirstead H.S., Nistor G., Bernal G., Totoiu M., Cloutier F., Sharp K., and Steward O. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J. Neurosci. 25 (2005) 4694-4705
37. Keller J.N., Huang F.F., and Markesbery W.R. Decreased levels of proteasome activity and proteasome expression in aging spinal cord. Neuroscience 98 (2000) 149-156
38. Koenig H.L., Schumacher M., Ferzaz B., Thi A.N., Ressouches A., Guennoun R., Jung-Testas I., Robel P., Akwa Y., and Baulieu E.E. Progesterone synthesis and myelin formation by Schwann cells. Science 268 (1995) 1500-1503
39. Kokaia Z., Othberg A., Kokaia M., and Lindvall O. BDNF makes cultured dentate granule cells more resistant to hypoglycaemic damage. Neuroreport 5 (1994) 1241-1244
40. Kovari E., Gold G., Herrmann F.R., Canuto A., Hof P.R., Michel J.P., Bouras C., and Giannakopoulos P. Cortical microinfarcts and demyelination significantly affect cognition in brain aging. Stroke 35 (2004) 410-414
41. Kullberg S., Ramirez-Leon V., Johnson H., and Ulfhake B. Decreased axosomatic input to motoneurons and astrogliosis in the spinal cord of aged rats. J. Gerontol. A. Biol. Sci. Med. Sci. 53 (1998) B369-B379
42. Kyrkanides S., O'Banion M.K., Whiteley P.E., Daeschner J.C., and Olschowka J.A. Enhanced glial activation and expression of specific CNS inflammation-related molecules in aged versus young rats following cortical stab injury. J. Neuroimmunol. 119 (2001) 269-277
43. Larsson E., Nanobashvili A., Kokaia Z., and Lindvall O. Evidence for neuroprotective effects of endogenous brain-derived neurotrophic factor after global forebrain ischemia in rats. J. Cereb. Blood Flow Metab. 19 (1999) 1220-1228
44. Lindvall O., Kokaia Z., Bengzon J., Elmer E., and Kokaia M. Neurotrophins and brain insults. Trends Neurosci. 17 (1994) 490-496
45. Luerssen T.G., Klauber M.R., and Marshall L.F. Outcome from head injury related to patient's age. A longitudinal prospective study of adult and pediatric head injury. J. Neurosurg. 68 (1988) 409-416
46. Mason J.L., Ye P., Suzuki K., D'Ercole A.J., and Matsushima G.K. Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination. J. Neurosci. 20 (2000) 5703-5708
47. Mason J.L., Xuan S., Dragatsis I., Efstratiadis A., and Goldman J.E. Insulin-like growth factor (IGF) signaling through type 1 IGF receptor plays an important role in remyelination. J. Neurosci. 23 (2003) 7710-7718
48. McTigue D.M., Horner P.J., Stokes B.T., and Gage F.H. Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord. J. Neurosci. 18 (1998) 5354-5365
49. Melcangi R.C., Magnaghi V., Cavarretta I., Martini L., and Piva F. Age-induced decrease of glycoprotein Po and myelin basic protein gene expression in the rat sciatic nerve. Repair by steroid derivatives. Neuroscience 85 (1998) 569-578
50. Moorthy K., Yadav U.C., Siddiqui M.R., Sharma D., Basir S.F., and Baquer N.Z. Effect of estradiol and progesterone treatment on carbohydrate metabolizing enzymes in tissues of aging female rats. Biogerontology 5 (2004) 249-259
51. Morales A.J., Haubrich R.H., Hwang J.Y., Asakura H., and Yen S.S. The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin. Endocrinol. (Oxf) 49 (1998) 421-432
52. Nakao N., Kokaia Z., Odin P., and Lindvall O. Protective effects of BDNF and NT-3 but not PDGF against hypoglycemic injury to cultured striatal neurons. Exp. Neurol. 131 (1995) 1-10
53. Nashmi R., and Fehlings M.G. Mechanisms of axonal dysfunction after spinal cord injury: with an emphasis on the role of voltage-gated potassium channels. Brain Res. Brain Res. Rev. 38 (2001) 165-191
54. Navarro A., and Boveris A. The mitochondrial energy transduction system and the aging process. Am. J. Physiol. Cell. Physiol. 292 (2007) C670-C686
55. Navarro A., and Boveris A. Brain mitochondrial dysfunction in aging: conditions that improve survival, neurological performance and mitochondrial function. Front. Biosci. 12 (2007) 1154-1163
56. NSCISC (National Spinal Cord Injury Statistical Center), 2006. Facts and Figures at a Glance. [Online]. Available: (accessed 23.02.06.).
57. Peters A. Age-associated changes in oligodendrocytes in monkey cerebral cortex. J. Comp. Neurol. 371 (1996) 153-163
58. Peters A., Moss M.B., and Sethares C. Effects of aging on myelinated nerve fibers in monkey primary visual cortex. J. Comp. Neurol. 419 (2000) 364-376
59. Peters A., Sethares C., and Killiany R.J. Effects of age on the thickness of myelin sheaths in monkey primary visual cortex. J. Comp. Neurol. 435 (2001) 241-248
60. Peters A., and Sethares C. Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey. J. Comp. Neurol. 442 (2002) 277-291
61. Peters A., and Sethares C. Is there remyelination during aging of the primate central nervous system?. J. Comp. Neurol. 460 (2003) 238-254
62. Popovich P.G., Wei P., and Stokes B.T. Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J. Comp. Neurol. 377 (1997) 443-464
63. Popovich P.G., Guan Z., Wei P., Huitinga I., van Rooijen N., and Stokes B.T. Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp. Neurol. 158 (1999) 351-365
64. Popovich P.G., Guan Z., McGaughy V., Fisher L., Hickey W.F., and Basso D.M. The neuropathological and behavioral consequences of intraspinal microglial/macrophage activation. J. Neuropathol. Exp. Neurol. 61 (2002) 623-633
65. Raz N., Lindenberger U., Rodrigue K.M., Kennedy K.M., Head D., Williamson A., Dahle C., Gerstorf D., and Acker J.D. Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb. Cortex. 15 (2005) 1676-1689
66. Raz N., and Rodrigue K.M. Differential aging of the brain: patterns, cognitive correlates and modifiers. Neurosci. Biobehav. Rev. 30 (2006) 730-748
67. Schumacher M., Guennoun R., Robert F., Carelli C., Gago N., Ghoumari A., Gonzalez Deniselle M.C., Gonzalez S.L., Ibanez C., Labombarda F., Coirini H., Baulieu E.E., and De Nicola A.F. Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination. Growth Horm. IGF Res. 14 Suppl. A (2004) S18-33
68. Scivoletto G., Morganti B., Ditunno P., Ditunno J.F., and Molinari M. Effects on age on spinal cord lesion pateients' rehabilitation. Spinal Cord 41 (2003) 457-464
69. Scivoletto G., Romanelli A., Mariotti A., Marinucci D., Tamburella F., Mammone A., Cosentino E., Sterzi S., and Molinari M. Clinical factors that affect walking level and performance in chronic spinal cord lesion patients. Spine 33 (2008) 259-264
70. Shields S.A., Gilson J.M., Blakemore W.F., and Franklin R.J. Remyelination occurs as extensively but more slowly in old rats compared to young rats following gliotoxin-induced CNS demyelination. Glia 28 (1999) 77-83
71. Sim F.J., Hinks G.L., and Franklin R.J. The re-expression of the homeodomain transcription factor Gtx during remyelination of experimentally induced demyelinating lesions in young and old rat brain. Neuroscience 100 (2000) 131-139
72. Siqueira I.R., Cimarosti H., Fochesatto C., Salbego C., and Netto C.A. Age-associated susceptibility to oxygen and glucose deprivation damage in rat hippocampal slices. Brain. Res. 1025 (2004) 226-230
73. Streit W.J. Microglial senescence: does the brain's immune system have an expiration date?. Trends Neurosci. 29 (2006) 506-510
74. Sturrock R.R. Changes in neurologia and myelination in the white matter of aging mice. J. Gerontol. 31 (1976) 513-522
75. Sutherland G.R., Dix G.A., and Auer R.N. Effect of age in rodent models of focal and forebrain ischemia. Stroke 27 (1996) 1663-1667 discussion 1668
76. Tanaka J., Okuma Y., Tomobe K., and Nomura Y. The age-associated degeneration of oligodendrocytes in the hippocampus of the senescence-accelerated mouse (SAM) P8: a quantitative immunohistochemical study. Biol. Pharm. Bull. 28 (2005) 615-618
77. Taoka Y., Okajima K., Uchiba M., Murakami K., Kushimoto S., Johno M., Naruo M., Okabe H., and Takatsuki K. Role of neutrophils in spinal cord injury in the rat. Neuroscience 79 (1997) 1177-1182
78. Teasdale G., Skene A., Parker L., and Jennett B. Age and outcome of severe head injury. Acta Neurochir. Suppl. (Wien) 28 (1979) 140-143
79. Totoiu M.O., and Keirstead H.S. Spinal cord injury is accompanied by chronic progressive demyelination. J. Comp. Neurol. 486 (2005) 373-383
80. Utzschneider D.A., Archer D.R., Kocsis J.D., Waxman S.G., and Duncan I.D. Transplantation of glial cells enhances action potential conduction of amyelinated spinal cord axons in the myelin-deficient rat. Proc. Natl. Acad. Sci. U. S. A. 91 (1994) 53-57
81. Veiga S., Garcia-Segura L.M., and Azcoitia I. Neuroprotection by the steroids pregnenolone and dehydroepiandrosterone is mediated by the enzyme aromatase. J. Neurobiol. 56 (2003) 398-406
82. Vollmer D.G., and Dacey Jr. R.G. The management of mild and moderate head injuries. Neurosurg. Clin. N. Am. 2 (1991) 437-455
83. Waxman S.G., Utzschneider D.A., and Kocsis J.D. Enhancement of action potential conduction following demyelination: experimental approaches to restoration of function in multiple sclerosis and spinal cord injury. Prog. Brain Res. 100 (1994) 233-243
84. Yager J.Y., Wright S., Armstrong E.A., Jahraus C.M., and Saucier D.M. The influence of aging on recovery following ischemic brain damage. Behav. Brain Res. 173 (2006) 171-180
85. Zhao C., Li W.W., and Franklin R.J. Differences in the early inflammatory responses to toxin-induced demyelination are associated with the age-associated decline in CNS remyelination. Neurobiol. Aging 27 (2006) 1298-1307