Systemic Administration of 17β-Estradiol Reduces Apoptotic Cell Death and Improves Functional Recovery Following Traumatic Spinal Cord Injury in Rats

Journal of Neurotrauma

Volumn 21, Issue 3, 2004, Pages 293-306

  Yune, Tae Y ^a   Kim, Sun J ^a   Lee, Sang M ^a   Lee, Young K ^a   Oh, Young J ^b   Kim, Young C ^c   Markelonis, George J ^d   Oh, Tae H ^d  

^a Korea Institute of Science and Technology   (South Korea)

^b Yonsei University   (South Korea)

^c Seoul National University   (South Korea)

^d UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

Apoptosis; BBB score; Bcl 2; Bcl x; Caspase 3; DNA laddering; Estrogen; Functional recovery; Lesion area; Neuroprotection; Spinal cord injury; TUNEL

Indexed keywords

CASPASE 3; ESTRADIOL; ESTROGEN; CASP3 PROTEIN, RAT; CASPASE; MESSENGER RNA; PROTEIN BCL 2;

ANIMAL BEHAVIOR; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BAD GENE; BASSO BEATTIE BRESNAHAN LOCOMOTOR OPEN FIELD BEHAVIOR RATING TEST; BAX GENE; BCL X GENE; BRAIN CONTUSION; CONTROLLED STUDY; ENZYME ACTIVITY; GEL ELECTROPHORESIS; GENE EXPRESSION; HINDLIMB; MOTOR PERFORMANCE; NEUROPROTECTION; NICK END LABELING; NONHUMAN; OPEN FIELD BEHAVIOR; PROTO ONCOGENE; RATING SCALE; SCORING SYSTEM; SPINAL CORD CONTUSION; SPINAL CORD INJURY; STAINING; ANIMAL; CONVALESCENCE; GENETICS; MALE; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; RAT; SPRAGUE DAWLEY RAT;

ANIMALS; APOPTOSIS; CASPASE 3; CASPASES; ESTRADIOL; MALE; PROTO-ONCOGENE PROTEINS C-BCL-2; RATS; RATS, SPRAGUE-DAWLEY; RECOVERY OF FUNCTION; RNA, MESSENGER; SPINAL CORD INJURIES;

EID: 1642482615     PISSN: 08977151     EISSN: None     Source Type: Journal    
DOI: 10.1089/089771504322972086     Document Type: Article

References (95)

1. ALKAYED, N.J., GOTO, S., SUGO, N., et al. (2001). Estrogen and Bcl-2: gene induction and effect of transgene in experimental stroke. J. Neurosci. 21, 7543-7550.
2. ALKAYED, N.J., HARUKUNI, I., KIMES, A.S., et al. (1998). Gender-linked brain injury in experimental stroke. Stroke 29, 159-165.
3. ANTONAWICH, F.J., FEDEROFF, H.J., and DAVIS, J.N. (1999). BCL-2 transduction, using a herpes simplex virus amplicon, protects hippocampal neurons from transient global ischemia. Exp. Neurol. 156, 130-137.
4. AZCOITIA, I., SIERRA, A., and GARCIA-SEGURA, L.M. (1998). Estradiol prevents kainic acid-induced neuronal loss in the rat dentate gyrus. Neuroreport 9, 3075-3079.
5. BALENTINE, J.D. (1978). Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury. Lab. Invest. 39, 236-253.
6. BASSO, D.M., BEATTIE, M.S., and BRESNAHAN, J.C. (1995). A sensitive and reliable locomotor rating scale for open field testing in rats. J. Neurotrauma 12, 1-21.
7. BASSO, D.M., BEATTIE, M.S., and BRESNAHAN, J.C. (1996a). Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp. Neurol. 139, 244-256.
8. BASSO, D.M., BEATTIE, M.S., BRESNAHAN, J.C., et al. (1996b). MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter Animal Spinal Cord Injury Study. J. Neurotrauma 13, 343-359.
9. BEATTIE, M.S., BRESNAHAN, J.C., KOMON, J., et al. (1997). Endogenous repair after spinal cord contusion injuries in the rat. Exp. Neurol. 148, 453-463.
10. BEATO, M. (1989). Gene regulation by steroid hormones. Cell 56, 335-344.
11. BEHL, C., SKUTELLA, T., LEZOUALC'H, F., et al. (1997). Neuroprotection against oxidative stress by estrogens: structure-activity relationship. Mol. Pharmacol. 51, 535-541.
12. CALLIER, S., MORISSETTE, M., GRANDBOIS, M., et al. (2000). Stereospecific prevention by 17beta-estradiol of MPTP-induced dopamine depletion in mice. Synapse 37, 245-251.
13. CASHA, S., YU, W.R., and FEHLINGS, M.G. (2001). Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat. Neuroscience 103, 203-218.
14. CHEN, J., GRAHAM, S.H., CHAN, P.H., et al. (1995). Bcl-2 is expressed in neurons that survive focal ischemia in the rat. Neuroreport 6, 394-398.
15. CHEN, J., GRAHAM, S.H., NAKAYAMA, M., et al. (1997). Apoptosis repressor genes Bcl-2 and Bcl-x-long are expressed in the rat brain following global ischemia. J. Cereb. Blood Flow Metab. 17, 2-10. [For erratum, see 1998;18: 931.]
16. CHEN, J., SIMON, R.P., NAGAYAMA, T., et al. (2000). Suppression of endogenous bcl-2 expression by antisense treatment exacerbates ischemic neuronal death. J. Cereb. Blood Flow Metab. 20, 1033-1039.
17. CITRON, B.A., ARNOLD, P.M., SEBASTIAN, C., et al. (2000). Rapid upregulation of caspase-3 in rat spinal cord after injury: mRNA, protein, and cellular localization correlates with apoptotic cell death. Exp. Neurol. 166, 213-226.
18. CROWE, M.J., BRESNAHAN, J.C., SHUMAN, S.L., et al. (1997). Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nat. Med. 3, 73-76.
19. CULMSEE, C., VEDDER, H., RAVATI, A., et al. (1999). Neuroprotection by estrogens in a mouse model of focal cerebral ischemia and in cultured neurons: evidence for a receptor-independent antioxidative mechanism. J. Cereb. Blood Flow Metab. 19, 1263-1269.
20. DARE, E., GOTZ, M.E., ZHIVOTOVSKY, B., et al. (2000). Antioxidants J811 and 17beta-estradiol protect cerebellar granule cells from methylmercury-induced apoptotic cell death. J. Neurosci. Res. 62, 557-565.
21. DISSHON, K.A., and DLUZEN, D.E. (1997). Estrogen as a neuromodulator of MPTP-induced neurotoxicity: effects upon striatal dopamine release. Brain Res. 764, 9-16.
22. DU, S., RUBIN, A., KLEPPER, S., et al. (1999). Calcium influx and activation of calpain I mediate acute reactive gliosis in injured spinal cord. Exp. Neurol. 157, 96-105.
23. DUBAL, D.B., KASHON, M.L., PETTIGREW, L.C., et al. (1998). Estradiol protects against ischemic injury. J. Cereb. Blood Flow Metab. 18, 1253-1258.
24. DUBAL, D.B., SHUGHRUE, P.J., WILSON, M.E., et al. (1999). Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors. J. Neurosci. 19, 6385-6393.
25. DUBAL, D.B., and WISE, P.M. (2001). Neuroprotective effects of estradiol in middle-aged female rats. Endocrinology 142, 43-48.
26. DLUZEN, D.E. (2000). Neuroprotective effects of estrogen upon the nigrostriatal dopaminergic system. J. Neurocytol. 29, 387-399.
27. EMERY, E., ALDANA, P., BUNGE, M.B., et al. (1998). Apoptosis after traumatic human spinal cord injury. J. Neurosurg. 89, 911-920.
28. FRIEDLANDER, R.M., and YUAN, J. (1998). ICE, neuronal apoptosis and neurodegeneration. Cell Death Differ. 5, 823-831.
29. GAIL, M.H., COSTANTINO, J.P., BRYANT, J., et al. (1999). Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer. J. Natl. Cancer Inst. 91, 1829-1846.
30. GARCIA-SERGUR, L.M., AZCOITIA, I., and DONCARLO, L.L. (2001). Neuroprotection by estradiol. Prog. Neurobiol. 63, 29-60.
31. GARCIA-SEGURA, L.M., CARDONA-GOMEZ, P., NAFTOLIN, F., et al. (1998). Estradiol upregulates Bcl-2 expression in adult brain neurons. Neuroreport 9, 593-597.
32. GOODMAN, Y., BRUCE, A.J., CHENG, B., et al. (1996). Estrogen attenuate and corticosteron exacerbates excitotoxicity, oxidative injury, and amyloid b-peptide toxicity in hippocampal neurons. J. Neurochem. 66, 1836-1844.
33. GOODMAN, S.B., KUGU, K., CHEN, S.H., et al. (1998). Estradiol-mediated suppression of apoptosis in the rabbit corpus luteum is associated with a shift in expression of bcl-2 family members favoring cellular survival. Biol. Reprod. 59, 820-827.
34. GREEN, P.S., BISHOP, J., and SIMPKINS, J.W. (1997). 17-Alpha-estradiol exerts neuroprotective effects on SK-N-SH cells. J. Neurosci. 17, 511-515.
35. GREENLUND, L.J., KORSMEYER, S.J., and JOHNSON, E.M. JR. (1995). Role of BCL-2 in the survival and function of developing and mature sympathetic neurons. Neuron 15, 649-661.
36. GRIDLEY, K.E., GREEN, P.S., and SIMPKINS, J.W. (1998). A novel, synergistic interaction between 17 beta-estradiol and glutathione in the protection of neurons against beta-amyloid 25-35-induced toxicity in vitro. Mol. Pharmacol. 54, 874-880.
37. GRUNER, J.A. (1992). A monitored contusion model of spinal cord injury in the rat. J. Neurotrauma 9, 123-128.
38. HALL, E.D., PAZARA, K.E., and LINSEMAN, K.L. (1991). Sex differences in postischemic neuronal necrosis in gerbils. J. Cereb. Blood Flow Metab. 11, 292-298.
39. HATA, R., GILLARDON, F., MICHAELIDIS, T.M., et al. (1999). Targeted disruption of the bcl-2 gene in mice exacerbates focal ischemic brain injury. Metab. Brain Dis. 14, 117-124.
40. HE, Z., HE, Y.J., DAY, A.L., et al. (2002). Proestrus levels of estradiol during transient global cerebral ischemia improves the histological outcome of the hippocampal CA1 region: perfusion-dependent and-independent mechanisms. J. Neurol. Sci. 193, 79-87.
41. HENDERSON, V.W., WATT, L., and BUCKWALTER, J.G. (1996). Cognitive skills associated with estrogen replacement in women with Alzheimer's disease. Psychoneuroendocrinology 21, 421-430.
42. HONDA, K., SAWADA, H., KIHARA, T., et al. (2000). Phosphatidylinositol 3-kinase mediates neuroprotection by estrogen in cultured cortical neurons. J. Neurosci. Res. 60, 321-327.
43. HONKANIEMI, J., MASSA, S.M., BRECKINRIDGE, M., et al. 1996). Global ischemia induces apoptosis-associated genes in hippocampus. Brain Res. Mol. Brain Res. 42, 79-88.
44. JOVER, T., TANAKA, H., CALDERONE, A., et al. (2002). Estrogen protects against global ischemia-induced neuronal death and prevents activation of apoptotic signaling cascades in the hippocampal CA1. J. Neurosci. 22, 2115-2124.
45. KAWAS, C., RESNICK, S., MORRISON, A., et al. (1997). A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging. Neurology 48, 1517-1521. [For erratum, see 1998;51:654.]
46. KITAGAWA, K., MATSUMOTO, M., TSUJIMOTO, Y., et al. (1998). Amelioration of hippocampal neuronal damage after global ischemia by neuronal overexpression of BCL-2 in transgenic mice. Stroke 29, 2616-2621.
47. LEE, Y.B., YUNE, T.Y., BAIK, S.Y., et al. (2000). Role of tumor necrosis factor-alpha in neuronal and glial apoptosis after spinal cord injury. Exp. Neurol. 166, 190-195.
48. LEE, S.M., YUNE, T.Y., KIM, S.J., et al. (2004). Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J. Neurotrauma (in press).
49. LI, G.L., BRODIN, G., FAROOQUE, et al. (1996). Apoptosis and expression of Bcl-2 after compression trauma to rat spinal cord. Exp. Neurol. 55, 280-289.
50. LI, M., ONA, V.O., CHEN, M., et al. (2000). Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury. Neuroscience 99, 333-342.
51. LI, Y.Q., and WONG, C.S. (2000). Radiation-induced apoptosis in the neonatal and adult rat spinal cord. Radiat. Res. 154, 268-276.
52. LINNIK, M.D., ZAHOS, P., GESCHWIND, M.D., et al. (1995). Expression of bcl-2 from a defective herpes simplex virus-1 vector limits neuronal death in focal cerebral ischemia. Stroke 26, 1670-1674.
53. LIU, X.Z., XU, X.M., HU, R., et al. (1997). Neuronal and glial apoptosis after traumatic spinal cord injury. J. Neurosci. 17, 5395-5406.
54. LU, A., RAN, R.Q., CLARK, J., et al. (2002). 17-Beta-estradiol induces heat shock proteins in brain arteries and potentiates ischemic heat shock protein induction in glia and neurons. J. Cereb. Blood Flow Metab. 22,183-195.
55. MACMANNUS, J.P., and LINNNIK, M.D. (1997). Gene expression induced by cerebral ischemia: an apoptotic perspective. J. Cereb. Blood Flow Metab. 17, 815-832.
56. MARTINOU, J.C., DUBOIS-DAUPHIN, M., STAPLE, J.K., et al. (1994). Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13, 1017-1030.
57. MATSUSHITA, K., WU, Y., QIU, J., et al. (2000). Fas receptor and neuronal cell death after spinal cord ischemia. J. Neurosci. 20, 6879-6887.
58. MERRY, D.E., and KORSMEYER, S.J. (1997). Bcl-2 gene family in the nervous system. Annu. Rev. Neurosci. 20, 245-267.
59. NESIC, O., XU, G.Y., MCADOO, D., et al. (2001). IL-1 receptor antagonist prevents apoptosis and caspase-3 activation after spinal cord injury. J. Neurotrauma 18, 947-956.
60. NUDEL, U., ZAKUT, R., SHANI, M., et al. (1983). The nucleotide sequence of the rat cytoplasmic beta-actin gene. Nucleic Acids Res. 11, 1759-1771.
61. ONA, V.O., LI, M., VONSATTEL, J.P., et al. (1999). Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature 399, 263-267.
62. PAGANINI-HILL, A. (1995). Estrogen replacement therapy and stroke. Prog. Cardiovasc. Dis. 38, 223-242.
63. PELLIGRINO, D.A., SANTIZO, R., BAUGHMAN, V.L., et al. (1998). Cerebral vasodilating capacity during forebrain ischemia: effects of chronic estrogen depletion and repletion and the role of neuronal nitric oxide synthase. Neuroreport 9, 285-3291.
64. PIKE, C.J. (1999). Estrogen modulates neuronal Bcl-XL expression and beta-amyloid-induced apoptosis: relevance to Alzheimer's disease. J. Neurochem. 72, 1552-1563.
65. REGAN, R.F., and GUO, Y. (1997). Estrogens attenuate neuronal injury due to hemoglobin, chemical hypoxia, and excitatory amino acids in murine cortical cultures. Brain Res. 764, 133-140.
66. RUSA, R., ALKAYED, N.J., CRAIN, B.J., et al. (1999). 17-Beta-estradiol reduces stroke injury in estrogen-deficient female animals. Stroke 30, 1665-1670.
67. SABOURIN, J.C., MARTIN, A., BARUCH, J., et al. (1994). bcl-2 expression in normal breast tissue during the menstrual cycle. Int. J. Cancer 59, 1-6.
68. SAWADA, H., IBI, M., KIHARA, T., et al. (1998). Estradiol protects mesencephalic dopaminergic neurons from oxidative stress-induced neuronal death. J. Neurosci. Res. 54, 707-719.
69. SAWADA, H., IBI, M., KIHARA, T., et al. (2000). Mechanisms of antiapoptotic effects of estrogens in nigral dopaminergic neurons. FASEB J. 14, 1202-1214.
70. SCHIELKE, G.P., YANG, G.Y., SHIVERS, B.D., et al. (1998). Reduced ischemic brain injury in interleukin-1 beta converting enzyme-deficient mice. J. Cereb. Blood Flow Metab. 18, 180-185.
71. SCHMIDT, R., FAZEKAS, F., REINHART, B., et al. (1996). Estrogen replacement therapy in older women: a neuropsychological and brain MRI study. J. Am. Geriatr. Soc. 44, 1307-1313.
72. SELINA, C.C., MCINTOSH, T.K., and NOBLE, L.J. (1989). Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations. Brain Res. 482, 271-282.
73. SHI, J., PANICKAR, K.S., YANG, S.H., et al. (1998). Estrogen attenuates over-expression of β-amyloid precursor protein messenger RNA in an animal model of focal ischemia. Brain Res. 810, 87-92.
74. SHIMAZAKI, K., ISHIDA, A., and KAWAI, N. (1994). Increase in bcl-2 oncoprotein and the tolerance to ischemia-induced neuronal death in the gerbil hippocampus. Neurosci. Res. 20, 95-99.
75. SHUMAN, S.L., BRESNAHAN, J.C., and BEATTIE, M.S. (1997). Apoptosis of microglia and oligodendrocytes after spinal cord contusion in rats. J. Neurosci. Res. 50, 798-808.
76. SIMPKINS, J.W., RAJAKUMAR, G., ZHANG, Y.Q., et al. (1997). Estrogens may reduce mortality and ischemic damage caused by middle cerebral artery occlusion in the female rat. J. Neurosurg. 87, 724-730.
77. SINGER, C.A., FIGUEROA-MASOT, X.A., BATCHELOR, R.H., et al. (1999). The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons. J. Neurosci. 19, 2455-2463.
78. SINGER, C.A., ROGERS, K.L., and DORSA, D.M. (1998). Modulation of Bcl-2 expression: a potential component of estrogen protection in NT2 neurons. Neuroreport 9, 2565-2568.
79. SINGER, C.A., ROGERS, K.L., STRICKLAND, T.M., et al. (1996). Estrogen protects primary cortical neurons from glutamate toxicity. Neurosci. Lett. 212, 13-16.
80. SPRINGER, J.E., AZBILL, R.D., and KNAPP, P.E. (1999). Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury. Nat. Med. 5, 943-946.
81. SPRINGER, J.E., AZBILL, R.D., NOTTINGHAM, S.A., et al. (2000). Calcineurin-mediated BAD dephosphorylation activates the caspase-3 apoptotic cascade in traumatic spinal cord injury. J. Neurosci. 20, 7246-7251.
82. SUDO, S., WEN, T.C., DESAKI, J., et al. (1997). Beta-estradiol protects hippocampal CA1 neurons against transient forebrain ischemia in gerbil. Neurosci. Res. 29, 345-354.
83. TANG, M.X., JACOBS, D., STERN, Y., et al. (1996). Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet. 348, 429-432.
84. THOMPSON, K.E., SIPES, I.G., GREENSTEIN, B.D., et al. (2002). 17-Beta-estradiol affords protection against 4-vinyl-cyclohexene diepoxide-induced ovarian follicle loss in Fischer-344 rats, Endocrinology 143, 1058-1065.
85. TOUNG, T.J., TRAYSTMAN, R.J., and HURN, P.D. (1998). Estrogen-mediated neuroprotection after experimental stroke in male rats. Stroke 29, 1666-1670.
86. VEDDER, H., ANTHES, N., STUMM, G., et al. (1999). Estrogen hormones reduce lipid peroxidation in cells and tissues of the central nervous system. J. Neurochem. 72, 2531-2538.
87. WEAVER, C.E., JR., PARK-CHUNG, M., GIBBS, T.T., et al. (1997). 17-Beta-Estradiol protects against NMDA-induced excitotoxicity by direct inhibition of NMDA receptors. Brain Res. 761, 338-341.
88. YAKOVLEV, A.G., and FADEN, A.I. (2001). Caspase-dependent apoptotic pathways in CNS injury. Mol. Neurobiol. 24, 131-144.
89. YAKOVLEV, A.G., KNOBLACH, S.M., FAN, L., et al. (1997). Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury. J. Neurosci. 17, 7415-7424.
90. YANG, S.H., SHI, J., DAY, A.L., et al. (2000). Estradiol exerts neuroprotective effects when administerd after ischemic insult. Stroke 31, 745-750.
91. YONG, C., ARNOLD, P.M., ZOUBINE, M.N., et al. (1998). Apoptosis in cellular compartments of rat spinal cord after severe contusion injury. J. Neurotrauma 15, 459-472.
92. YUAN, J., and YANKNER, B.A. (2000). Apoptosis in the nervous system. Nature 407, 802-809.
93. YUNE, T.Y., CHANG, M,J., KIM, S.J., et al. (2003). Increased production of tumor necrosis factor-alpha induces apoptosis after traumatic spinal cord injury in rats. J. Neurotrauma 20, 207-219.
94. ZAULYANOV, L.L., GREEN, P.S., and SIMPKINS, J.W. (1999). Glutamate receptor requirement for neuronal death from anoxia-reoxygenation: an in vitro model for assessment of the neuroprotective effects of estrogens. Cell Mol. Neurobiol. 19, 705-718.
95. ZHANG, Y.Q., SHI, J., RAZAKUMAR, G., et al. (1998). Effects of gender and estradiol treatment on focal brain ischemia. Brain Res. 784, 321-324.