Fiore Christelle, Inman Denise M, Hirose Shijiro, Noble Linda J, Igarashi Takuji, Compagnone Natalie A
Department of Neurological Surgery, Laboratory for Spinal cord Development and Regeneration, University of California, San Francisco, California, USA.
J Neurosci Res. 2004 Feb 1;75(3):391-400. doi: 10.1002/jnr.10821.
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.
神经甾体脱氢表雄酮（DHEA）在大脑遭受缺血性和兴奋性损伤后具有神经保护特性。在发育中的胚胎中，它在中枢神经系统（CNS）的离散区域产生，在那里它特别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建立并表征的中度挫伤性SCI模型。手术后立即用DHEA或仅用赋形剂进行治疗，并在42天的时间内比较治疗组（每组n = 12）。根据爪印记录的步态分析和倾斜梯梁上的足部失误分析，使用标准化的21分量表在开放场地评估运动恢复情况。在这些测试中，与赋形剂治疗的动物相比，DHEA治疗组的功能有所改善。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。为了将不同实验组的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 spared 白质的面积和反应性胶质增生/瘢痕形成情况。DHEA显著增加了震中处 spared 白质的面积，并减少了损伤周围反应性胶质增生的面积。这些数据证明了DHEA在促进成年小鼠脊髓损伤后功能恢复方面的有效性。
