Alterations in chondroitin sulfate proteoglycan expression occur both at and far from the site of spinal contusion injury

被引:98
作者
Andrews, Ellen M. [1 ,2 ,6 ]
Richards, Rebekah J. [1 ,2 ]
Yin, Feng Q. [1 ,2 ,6 ]
Viapiano, Mariano S. [2 ,3 ,4 ,5 ]
Jakeman, Lyn B. [1 ,2 ,3 ,6 ]
机构
[1] Ohio State Univ, Dept Physiol & Cell Biol, Med Ctr, Columbus, OH 43210 USA
[2] James Comprehens Canc Ctr, Columbus, OH 43210 USA
[3] Ohio State Univ, Dept Neurol Surg, Med Ctr, Columbus, OH 43210 USA
[4] Ohio State Univ, Dept Neurosci, Med Ctr, Columbus, OH 43210 USA
[5] Ohio State Univ, Dept Ctr Mol Neurobiol, Med Ctr, Columbus, OH 43210 USA
[6] Ohio State Univ, Ctr Brain & Spinal Cord Repair, Med Ctr, Columbus, OH 43210 USA
关键词
Neurocan; Aggrecan; NG2; CSPG; Perineuronal net; Spinal cord injury; Plasticity; INHIBIT NEURITE OUTGROWTH; CORD-INJURY; AXON-GROWTH; EXTRACELLULAR-MATRIX; NERVOUS-SYSTEM; CNS INJURY; GLIAL SCAR; WALLERIAN DEGENERATION; FUNCTIONAL RECOVERY; INTACT AGGRECAN;
D O I
10.1016/j.expneurol.2011.09.008
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
Chondroitin sulfate proteoglycans (CSPGs) present an inhibitory barrier to axonal growth and plasticity after trauma to the central nervous system. These extracellular and membrane bound molecules are altered after spinal cord injuries, but the magnitude, time course, and patterns of expression following contusion injury have not been fully described. Western blots and immunohistochemistry were combined to assess the expression of four classically inhibitory CSPGs, aggrecan, neurocan, brevican and NG2, at the lesion site and in distal segments of cervical and thoracic spinal cord at 3, 7, 14 and 28 days following a severe mid-thoracic spinal contusion. Total neurocan and the full-length (250 kDa) isoform were strongly upregulated both at the lesion epicenter and in cervical and lumbar segments. In contrast, aggrecan and brevican were sharply reduced at the injury site and were unchanged in distal segments. Total NG2 protein was unchanged across the injury site, while NG2+ profiles were distributed throughout the lesion site by 14 days post-injury (dpi). Far from the lesion, NG2 expression was increased at lumbar, but not cervical spinal cord levels. To determine if the robust increase in neurocan at the distal spinal cord levels corresponded to regions of increased astrogliosis, neurocan and GFAP immunoreactivity were measured in gray and white matter regions of the spinal enlargements. GFAP antibodies revealed a transient increase in reactive astrocyte staining in cervical and lumbar cord, peaking at 14 dpi. In contrast, neurocan immunoreactivity was specifically elevated in the cervical dorsal columns and in the lumbar ventral horn and remained high through 28 dpi. The long lasting increase of neurocan in gray matter regions at distal levels of the spinal cord may contribute to the restriction of plasticity in the chronic phase after SCI. Thus, therapies targeted at altering this CSPG both at and far from the lesion site may represent a reasonable addition to combined strategies to improve recovery after SCI. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:174 / 187
页数:14
相关论文
共 104 条
[1]
Schwann Cell Migration is Integrin-Dependent and Inhibited by Astrocyte-Produced Aggrecan [J].
Afshari, Fardad T. ;
Kwok, Jessica C. ;
White, Linda ;
Fawcett, James W. .
GLIA, 2010, 58 (07) :857-869
[2]
Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats [J].
Ankeny, DP ;
McTigue, DM ;
Jakeman, LB .
EXPERIMENTAL NEUROLOGY, 2004, 190 (01) :17-31
[3]
Asher RA, 2000, J NEUROSCI, V20, P2427
[4]
Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury [J].
Barritt, A. W. ;
Davies, M. ;
Marchand, F. ;
Hartley, R. ;
Grist, J. ;
Yip, P. ;
McMahon, S. B. ;
Bradbury, E. J. .
JOURNAL OF NEUROSCIENCE, 2006, 26 (42) :10856-10867
[5]
Brevican distinctively assembles extracellular components at the large diameter nodes of Ranvier in the CNS [J].
Bekku, Yoko ;
Rauch, Uwe ;
Ninomiya, Yoshifumi ;
Oohashi, Toshitaka .
JOURNAL OF NEUROCHEMISTRY, 2009, 108 (05) :1266-1276
[6]
A RANDOMIZED, CONTROLLED TRIAL OF METHYLPREDNISOLONE OR NALOXONE IN THE TREATMENT OF ACUTE SPINAL-CORD INJURY - RESULTS OF THE 2ND NATIONAL ACUTE SPINAL-CORD INJURY STUDY [J].
BRACKEN, MB ;
SHEPARD, MJ ;
COLLINS, WF ;
HOLFORD, TR ;
YOUNG, W ;
BASKIN, DS ;
EISENBERG, HM ;
FLAMM, E ;
LEOSUMMERS, L ;
MAROON, J ;
MARSHALL, LF ;
PEROT, PL ;
PIEPMEIER, J ;
SONNTAG, VKH ;
WAGNER, FC ;
WILBERGER, JE ;
WINN, HR .
NEW ENGLAND JOURNAL OF MEDICINE, 1990, 322 (20) :1405-1411
[7]
Chondroitinase ABC promotes functional recovery after spinal cord injury [J].
Bradbury, EJ ;
Moon, LDF ;
Popat, RJ ;
King, VR ;
Bennett, GS ;
Patel, PN ;
Fawcett, JW ;
McMahon, SB .
NATURE, 2002, 416 (6881) :636-640
[8]
Three-Dimensional Computer-Assisted Analysis of Graded Contusion Lesions in the Spinal Cord of the Rat [J].
Bresnahan, Jacqueline C. ;
Beattie, Michael S. ;
Stokes, Bradford T. ;
Conway, Kevin M. .
JOURNAL OF NEUROTRAUMA, 1991, 8 (02) :91-101
[9]
BUNGE RP, 1993, ADV NEUROL, V59, P75
[10]
Gradual loss of myelin and formation of an astrocytic scar during Wallerian degeneration in the human spinal cord [J].
Buss, A ;
Brook, GA ;
Kakulas, B ;
Martin, D ;
Franzen, R ;
Schoenen, J ;
Noth, J ;
Schmitt, AB .
BRAIN, 2004, 127 :34-44