Treatment with the neurosteroid dehydroepiandrosterone promotes recovery of motor behavior after moderate contusive spinal cord injury in the mouse
Treatment with the neurosteroid dehydroepiandrosterone promotes recovery of motor behavior after moderate contusive spinal cord injury in the mouse
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DOI：
10.1002/jnr.10821
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发表时间：
2004-02-01
影响因子：
4.2
通讯作者：
Compagnone, NA
中科院分区：
文献类型：
--
作者：
Fiore, C;Inman, DM;Compagnone, NA
神经甾体脱氢表雄酮（DHEA）在缺血性和兴奋性脑损伤后具有神经保护作用。在发育中的胚胎中，它产生于中枢神经系统（CNS）的离散区域，在那里它特异性地促进分化神经元的轴突生长。为了测试DHEA在脊髓损伤（SCI）后是否有益，我们使用了在小鼠中开发和表征的中度挫伤性SCI模型。手术后，我们立即应用DHEA或仅用溶剂治疗，并在42天内比较治疗组（每组n = 12）。运动恢复进行了评估，在一个开放的领域，使用标准化的21点的规模，根据步态分析爪印记录和使用脚故障分析，在倾斜的梯子梁。在这些测试中，与媒介物处理的动物相比，DHEA处理组显示出改善的功能。更引人注目的是，DHEA增强了左右协调和精细运动控制的恢复。在不同实验组中，为了将功能恢复与脊髓神经病理学相关联，我们研究了损伤后42天（DPI）震中处的备用白色物质和反应性胶质增生/瘢痕形成的面积。脱氢表雄酮显著增加了在震中保留的白色物质的面积，并减少了病变周围反应性胶质增生的面积。这些数据证明了DHEA在促进成年小鼠损伤脊髓的功能恢复中的有效性。(C)2003 Wiley-Liss，Inc.
The neurosteroid dehydroepiandrosterone (DHEA) has neuroprotective properties after ischemic and excitatory insults to the brain. In the developing embryo, it is produced in discrete regions of the central nervous system (CNS), where it specifically promotes axonal growth of differentiated neurons. To test if DHEA could be beneficial after spinal cord injury (SCI), we used a model of moderate contusive SCI developed and characterized in the mouse. Immediately after surgery, we applied treatment with DHEA or with vehicle only and compared treatment groups (n = 12 in each group) over a 42-day period. Locomotor recovery was assessed in an open field using a standardized 21-point scale, according to gait analysis on paw print recordings and using foot fault analyses, on an inclined ladder beam. The DHEA-treated group showed improved function compared to vehicle-treated animals in these tests. More strikingly, DHEA enhanced recovery of left-right coordination and fine motor control. In an attempt to correlate functional recovery with spinal cord neuropathology in the different experimental groups, we studied the area of spared white matter at the epicenter and reactive gliosis/scar formation 42 days post-injury (DPI). DHEA significantly increased the area of white matter spared at the epicenter and reduced the area of reactive gliosis surrounding the lesion. These data demonstrate the effectiveness of DHEA in promoting functional recovery in the adult murine injured spinal cord. (C) 2003 Wiley-Liss, Inc.