title: 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.
abstract: Spinal cord injury (SCI), depending on the severity of injury, leads to neurological dysfunction and paralysis. Methylprednisolone, the only currently available therapy renders limited protection in SCI. Therefore, other therapeutic agents must be tested to maximize neuroprotection and functional recovery. Previous data from our laboratory indicate that estrogen (17β-estradiol) at a high dose may attenuate multiple damaging pathways involved in SCI and improve locomotor outcome. Since use of high dose estrogen may have detrimental side effects and therefore may never be used in the clinic, the current study investigated the efficacy of this steroid hormone at very low doses in SCI. In particular, we tested the impact of dosing (1-10 μg/kg), mode of delivery (intravenous vs. osmotic pump), and delay in estrogen application (15 min-4 h post-SCI) on microgliosis and neuronal death in acute SCI in rats. Treatment with 17β-estradiol (1-10 μg/kg) significantly reduced microglial activation and also attenuated apoptosis of neurons compared to untreated SCI animals. The attenuation of cell death and inflammation by estrogen was observed regardless of mode and time of delivery following injury. These findings suggest estrogen as a potential agent for the treatment of individuals with SCI.
authors: Division of Neurology, Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309, Clinical Sciences Building, PO Box 250606, Charleston, SC 29425, USA.
authors: Supriti
authors: S
authors: Samantaray
authors: Joshua A
authors: JA
authors: Smith
authors: Arabinda
authors: A
authors: Das
authors: Denise D
authors: DD
authors: Matzelle
authors: Abhay K
authors: AK
authors: Varma
authors: Swapan K
authors: SK
authors: Ray
authors: Naren L
authors: NL
authors: Banik
references: Brain Res. 2009 Jun 18;1276:159-70
references: 19389388
references: J Neurosci Res. 2005 Oct 15;82(2):283-93
references: 16130149
references: Biochem J. 1996 Nov 1;319 ( Pt 3):683-90
references: 8920967
references: Trials. 2009 Aug 24;10:77
references: 19703282
references: J Thorac Cardiovasc Surg. 2003 Feb;125(2):370-7
references: 12579107
references: Exp Neurol. 1983 Jun;80(3):561-72
references: 6852152
references: Brain Res. 1981 May 4;211(2):476-9
references: 7237138
references: J Biol Chem. 2001 Mar 30;276(13):10191-8
references: 11124942
references: Curr Drug Targets CNS Neurol Disord. 2003 Jun;2(3):173-89
references: 12769798
references: J Neuroimmunol. 2005 Apr;161(1-2):123-36
references: 15748951
references: Brain Res. 2008 Apr 8;1203:177-88
references: 18316064
references: Ann N Y Acad Sci. 2010 Jun;1199:86-9
references: 20633112
references: Spine (Phila Pa 1976). 2003 May 1;28(9):941-7; discussion 947
references: 12942012
references: J Neuropathol Exp Neurol. 2003 Jun;62(6):633-43
references: 12834108
references: Neurochem Res. 2004 Nov;29(11):2007-14
references: 15662835
references: J Neurosci Res. 2003 Jul 1;73(1):95-104
references: 12815713
references: J Pineal Res. 2008 May;44(4):348-57
references: 18086148
references: Nutrition. 2005 Jun;21(6):775-7
references: 15925305
references: Free Radic Biol Med. 1999 Aug;27(3-4):478-82
references: 10468225
references: Brain Res Brain Res Protoc. 2000 Jul;5(3):305-11
references: 10906497
references: J Neurosci Res. 2010 Jun;88(8):1738-50
references: 20091771
references: Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8867-72
references: 10430862
references: Neuroscience. 2000;99(1):179-88
references: 10924962
references: Front Neuroendocrinol. 2009 Jul;30(2):201-11
references: 19401209
references: J Neurotrauma. 2004 Mar;21(3):293-306
references: 15115604
references: J Cell Biochem. 2000 Sep 18;80(1):53-72
references: 11029754
references: Ann N Y Acad Sci. 2003 May;993:125-33; discussion 159-60
references: 12853305
references: J Neurotrauma. 2000 Oct;17(10):871-90
references: 11063054
references: Neuroreport. 1998 Aug 3;9(11):2437-42
references: 9721910
references: Neurochem Res. 2007 Dec;32(12):2210-6
references: 17676387
references: Prog Neurobiol. 1998 Mar;54(4):369-415
references: 9522394
references: Ann N Y Acad Sci. 2010 Jun;1199:90-4
references: 20633113
references: J Neurosci Res. 2006 Oct;84(5):1064-75
references: 16902996
references: J Neurophysiol. 2000 Aug;84(2):1116-9
references: 10938336
references: J Neurotrauma. 2007 Mar;24(3):473-80
references: 17402853
references: Neuroreport. 2000 Sep 28;11(14):3067-70
references: 11043525
references: Exp Neurol. 1998 May;151(1):77-88
references: 9582256
references: J Neurotrauma. 2011 Aug;28(8):1545-88
references: 20146558
references: J Neurosurg. 2000 Jul;93(1 Suppl):1-7
references: 10879751
references: J Neurosci Res. 2004 Jun 1;76(5):688-96
references: 15139027
references: J Neurotrauma. 2006 Jun;23(6):830-52
references: 16774470
references: Cent Nerv Syst Trauma. 1987;4(3):149-59
references: 3442814
references: J Neurochem. 1997 Oct;69(4):1592-600
references: 9326288
references: Neuroscience. 1993 Nov;57(2):443-9
references: 8115048
references: Front Neuroendocrinol. 2009 Jul;30(2):142-57
references: 19410597
references: Clin Neuropharmacol. 2001 Sep-Oct;24(5):265-79
references: 11586111
references: Neurosurg Rev. 1993;16(1):53-9
references: 8483520
references: J Neurosci Res. 1994 Mar 1;37(4):489-96
references: 7517457
references: JAMA. 1984 Jan 6;251(1):45-52
references: 6361287
references: Neurochem Res. 2000 Oct;25(9-10):1191-8
references: 11059793
references: Cent Nerv Syst Trauma. 1985 Summer;2(2):109-14
references: 2420480
references: Semin Reprod Med. 2009 May;27(3):240-9
references: 19401955