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

Alterations in chondroitin sulfate proteoglycan expression occur both at and far from the site of spinal contusion injury.
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DOI:
10.1016/j.expneurol.2011.09.008
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发表时间:
2012-05
影响因子:
5.3
通讯作者:
Jakeman, Lyn B.
Jakeman, Lyn B.
中科院分区:
医学2区
文献类型:
--
作者:
Andrews, Ellen M.;Richards, Rebekah J.;Yin, Feng Q.;Viapiano, Mariano S.;Jakeman, Lyn B.

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硫酸软骨素蛋白聚糖(CSPGs)是中枢神经系统创伤后轴突生长和可塑性的抑制性屏障。这些细胞外和膜结合分子在脊髓损伤后发生改变,但挫伤后表达的幅度、时间过程和模式尚未完全描述。采用免疫印迹法和免疫组化法检测严重胸中段脊髓挫伤后3、7、14和28 d 4种典型抑制性CSPGs(aggrecan、neurocan、brevican和NG2)在损伤部位和颈胸段脊髓远段的表达。总神经蛋白聚糖和全长(250 kDa)亚型强烈上调病变震中和颈椎和腰椎段。相反,聚集蛋白聚糖和短蛋白聚糖在损伤部位急剧减少,在远端节段无变化。到损伤后14天(dpi),损伤部位的总NG 2蛋白没有变化,而NG 2+分布在整个损伤部位。远离病变,NG2表达增加,在腰椎,但不是颈脊髓水平。为了确定在远端脊髓水平神经聚糖的稳健增加是否对应于星形胶质细胞增生增加的区域,在脊髓扩大的灰色和白色物质区域中测量神经聚糖和GFAP免疫反应性。GFAP抗体显示在颈髓和腰髓中反应性星形胶质细胞染色的短暂增加,在14 dpi达到峰值。相比之下,神经胶免疫反应性在颈椎背柱和腰椎腹角中特异性升高,并在28 dpi内保持较高水平。脊髓远端灰质区神经蛋白聚糖的长期增加可能与SCI后慢性期可塑性的限制有关。因此,针对改变损伤部位和远离损伤部位的CSPG的治疗可能是改善SCI后恢复的联合策略的合理补充。
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.
软骨素酶ABC促进脊髓损伤后完整和受伤的脊柱系统的发芽。
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发表时间: 2006-10-18
期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子: --
作者:
Barritt AW;Davies M;Marchand F;Hartley R;Grist J;Yip P;McMahon SB;Bradbury EJ
通讯作者: Bradbury EJ
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发表时间: 2010-02-23
期刊: SCIENCE SIGNALING
影响因子: 7.3
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Duan, Yuntao;Giger, Roman J.
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发表时间: 2006-12-01
期刊: BRAIN
影响因子: 14.5
作者:
Fleming, Jennifer C.;Norenberg, Michael D.;Weaver, Lynne C.
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发表时间: 2004-11-01
影响因子: 5.3
作者:
Ankeny, DP;McTigue, DM;Jakeman, LB
通讯作者: Jakeman, LB
DOI: 10.1093/brain/awl374
发表时间: 2007-04-01
期刊: BRAIN
影响因子: 14.5
作者:
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