Enhanced axonal growth into a spinal cord contusion injury site in a strain of mouse (129X1/SvJ) with a diminished inflammatory response

Enhanced axonal growth into a spinal cord contusion injury site in a strain of mouse (129X1/SvJ) with a diminished inflammatory response
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DOI:
10.1002/cne.20149
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发表时间:
2004-07-05
影响因子:
2.5
通讯作者:
Jakeman, LB
Jakeman, LB
中科院分区:
医学3区
文献类型:
--
作者:
Ma, MH;Wei, P;Jakeman, LB

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在成年中枢神经系统损伤后,侵入细胞和内在细胞有助于形成轴突生长难治的损伤部位。为了检验对创伤的炎症反应决定脊髓损伤后轴突生长的程度这一假设,在两种小鼠品系中比较了病变演变的时间过程,其中两种小鼠品系对外周炎症刺激具有对比的细胞反应。成年C57 B1/6和129 X1/SvJ小鼠接受相同的胸中脊髓挫伤,并允许恢复6小时至9周。两种菌株的反应都是趋化因子表达的快速、短暂增加,但在129 X1/SvJ小鼠中,这种早期反应的幅度略有降低。在伤后第一周,炎症的形态学指标相似。然而,伤后7天,细胞反应不同的菌株。C57 B1/6病变核心长期被巨噬细胞占据,缺乏星形胶质细胞,并且包含很少的轴突轮廓。相反,随着巨噬细胞密度的降低,星形胶质细胞突起和中枢和外周起源的轴突网络侵入129 X1 Sv/J小鼠病变部位的中心。129 X1 Sv/J小鼠轴突的生长伴随着病变核心血管外层粘连蛋白的增加和病变周边硫酸软骨素蛋白聚糖糖胺聚糖侧链的表达减少。这些结果表明,129 X1/SvJ小鼠中慢性炎症反应的减弱与脊髓损伤后细胞修复的增强和轴突生长的增加有关。(C)2004 Wiley-Liss,Inc.
After injury in the adult central nervous system, invading and intrinsic cells contribute to the formation of a lesion site that is refractory to axonal growth. To test the hypothesis that the inflammatory response to trauma dictates the extent of axonal growth after spinal cord injury, the time course of lesion evolution was compared in two mouse strains with contrasting cellular responses to peripheral inflammatory challenge. Adult C57Bl/6 and 129X1/SvJ mice received identical contusion injuries to the mid-thoracic spinal cord and were allowed to recover for 6 hours to 9 weeks. Both strains responded with a rapid, transient increase in chemokine expression, but the magnitude of this early response was slightly reduced in the 129X1/SvJ mice. Morphological indicators of inflammation were similar during the first week postinjury. After 7 days postinjury, however, the cellular responses differed between strains. The C57Bl/6 lesion core was chronically occupied by macrophages, devoid of astrocytes, and contained few axonal profiles. In contrast, as the macrophage density decreased a network of astrocytic processes and axons of central and peripheral origin invaded the center of the lesion site in 129X1Sv/J mice. Growth of axons in the 129X1Sv/J mice was accompanied by increased extravascular laminin in the lesion core and a reduced expression of chondroitin sulfate proteoglycan glycosaminoglycan sidechains in the periphery of the lesion. These results demonstrate that the diminished chronic inflammatory response in 129X1/SvJ mice is associated with enhanced cellular repair and increased axonal growth after spinal cord injury. (C) 2004 Wiley-Liss, Inc.