title: A reassessment of whether cortical motor neurons die following spinal cord injury.
abstract: Over the past century, the question of whether the cells of origin of the corticospinal tract (CST) die following spinal cord injury (SCI) has been debated. A recent study reported an approximately 20% loss of retrogradely labeled cortical motoneurons following damage to their axons resulting from SCI at T9 (Hains et al. [2003] J. Comp. Neurol. 462:328-341). In follow-up studies, however, we failed to find any evidence of loss of CST axons in the medullary pyramid, which must occur if CST neurons die. Here, we seek to resolve the discrepancy by re-evaluating possible loss of CST neurons using the same techniques as Hains et al. (quantitative analysis of retrograde labeling and staining for cell death markers including TUNEL and Hoechst labeling of the nuclei). Following either dorsal funiculus lesions at thoracic level 9 (T9) or lateral hemisection at cervical level 5 (C5), our results reveal no evidence for a loss of retrogradely labeled neurons and no evidence for TUNEL staining of axotomized cortical motoneurons. These results indicate that CST cell bodies do not undergo retrograde cell death following SCI, and therefore targeting such cell death is not a valid therapeutic target.
authors: Reeve-Irvine Research Center, University of California at Irvine, Irvine, California 92697, USA.
authors: Jessica L
authors: JL
authors: Nielson
authors: Melissa K
authors: MK
authors: Strong
authors: Oswald
authors: O
authors: Steward
references: Eur J Neurosci. 1997 Aug;9(8):1763-72
references: 9283831
references: Neuroscience. 1999;88(4):1267-74
references: 10336135
references: J Comp Neurol. 2009 Aug 20;515(6):647-63
references: 19496169
references: Proc R Soc Med. 1909;2(Neurol Sect):92-100
references: 19973799
references: J Anat. 1956 Jan;90(1):42-62
references: 13295151
references: Eur J Neurosci. 2003 Aug;18(4):789-802
references: 12925005
references: Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281-94
references: 4110397
references: Brain Res. 2004 Sep 10;1020(1-2):37-44
references: 15312785
references: J Cell Biol. 1992 Nov;119(3):493-501
references: 1400587
references: J Comp Neurol. 1990 Sep 8;299(2):167-77
references: 2229477
references: Exp Neurol. 2006 Apr;198(2):483-99
references: 16494866
references: J Neurosci. 2010 Jul 21;30(29):9728-37
references: 20660255
references: J Neurosci. 2009 Nov 25;29(47):14932-41
references: 19940189
references: Methods Achiev Exp Pathol. 1988;13:18-54
references: 3045494
references: Nat Neurosci. 2010 Dec;13(12):1505-10
references: 21076427
references: J Neurosci Methods. 2006 Apr 15;152(1-2):156-62
references: 16246425
references: J Neurosci Res. 1991 Sep;30(1):213-25
references: 1724469
references: J Neuropathol Exp Neurol. 1988 Jan;47(1):62-74
references: 3275429
references: Neuroscience. 1980;5(3):515-28
references: 6892841
references: Neuroscience. 1983 Dec;10(4):1301-15
references: 6141539
references: Reg Anesth Pain Med. 1999 Jan-Feb;24(1):59-67
references: 9952097
references: Brain Res Bull. 1993;30(3-4):469-75
references: 8457896
references: Brain Res Bull. 2005 Aug 15;66(3):203-11
references: 16023917
references: Prog Neurobiol. 1998 Apr;54(5):499-530
references: 9550189
references: J Neurosci. 2008 Aug 6;28(32):7936-44
references: 18685019
references: J Neurosci Methods. 2000 Jul 31;100(1-2):105-15
references: 11040372
references: Neuroreport. 1999 Aug 20;10(12):2671-5
references: 10574390
references: J Neurosci Res. 1991 Feb;28(2):182-91
references: 2033647
references: Nat Neurosci. 2004 Mar;7(3):269-77
references: 14966523
references: BMC Neurosci. 2008 Jan 14;9:5
references: 18194520
references: Cereb Cortex. 2009 Jan;19(1):224-32
references: 18483004
references: J Comp Neurol. 2008 Apr 20;507(6):1979-89
references: 18273888
references: Eur J Neurosci. 1996 Jun;8(6):1167-75
references: 8752586
references: J Neurotrauma. 2005 Jun;22(6):703-17
references: 15941378
references: Spine (Phila Pa 1976). 2007 May 15;32(11):1164-73
references: 17495772
references: Brain Res. 2001 Jul 6;906(1-2):127-34
references: 11430869
references: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3246-51
references: 11867727
references: Neuroscience. 1985 Feb;14(2):375-403
references: 2859548
references: J Neurotrauma. 2004 Jan;21(1):73-82
references: 14987467
references: J Comp Neurol. 2009 Oct 20;516(6):493-506
references: 19672995
references: Exp Neurol. 1990 Apr;108(1):83-5
references: 1690666
references: Neurology. 2002 Mar 12;58(5):794-801
references: 11889245
references: J Neurosci Res. 1985;14(1):71-81
references: 4020899
references: J Comp Neurol. 2008 Sep 1;510(1):24-46
references: 18615501
references: Exp Neurol. 2008 Feb;209(2):446-68
references: 18234196
references: Glia. 2006 Mar;53(4):352-9
references: 16288464
references: Neurology. 1983 Apr;33(4):478-82
references: 6682195
references: J Comp Neurol. 1997 Sep 22;386(2):293-303
references: 9295153
references: Brain Res. 2004 Nov 26;1028(1):19-25
references: 15518637
references: Neuroscience. 1998 Feb;82(3):709-25
references: 9483530
references: Brain Res. 1980 Nov 3;200(2):481-7
references: 7417826
references: J Neurophysiol. 1996 Jan;75(1):248-67
references: 8822555
references: Brain Res. 2004 Aug 13;1017(1-2):172-83
references: 15261113
references: Exp Neurol. 2005 Oct;195(2):524-39
references: 16051217
references: Brain Res. 1975 May 16;89(1):15-27
references: 1148840
references: Nat Rev Neurosci. 2006 Aug;7(8):628-43
references: 16858391
references: J Neurosci. 2010 Aug 25;30(34):11516-28
references: 20739574
references: Eur J Neurosci. 2005 Dec;22(12):3047-58
references: 16367771
references: Neurosci Lett. 1985 Aug 5;58(3):283-6
references: 4047489
references: BMC Neurosci. 2005 Aug 31;6:56
references: 16135243
references: J Neurophysiol. 1986 Mar;55(3):425-48
references: 3514812
references: J Neurosci. 2008 Dec 24;28(52):14107-20
references: 19109493
references: J Comp Neurol. 1985 Jul 22;237(4):506-18
references: 4044897
references: Neuropharmacology. 2000 Oct;39(13):2792-8
references: 11044749
references: J Comp Neurol. 2009 Jun 1;514(4):387-402
references: 19330821
references: J Pathol. 1995 May;176(1):27-35
references: 7542332
references: Exp Neurol. 2005 Jul;194(1):161-74
references: 15899253
references: Neurorehabil Neural Repair. 2007 Nov-Dec;21(6):527-38
references: 17507643
references: J Neuropathol Exp Neurol. 1979 Mar;38(2):128-51
references: 261986
references: J Comp Neurol. 1990 Jun 15;296(3):506-16
references: 2358550
references: Exp Brain Res. 1987;67(2):339-51
references: 3622693
references: Brain Res. 2008 Dec 3;1243:146-51
references: 18838063
references: Nature. 2002 Apr 11;416(6881):636-40
references: 11948352
references: J Microsc. 1988 Jul;151(Pt 1):3-21
references: 3193456
references: J Comp Neurol. 1956 Dec;106(2):527-55
references: 13416406
references: J Comp Neurol. 2003 Jun 9;462(3):328-41
references: 12794736
references: J Neurosci. 2008 Sep 17;28(38):9386-403
references: 18799672