A neuroprotective role of glial cell line-derived neurotrophic factor following moderate spinal cord contusion injury
A neuroprotective role of glial cell line-derived neurotrophic factor following moderate spinal cord contusion injury
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DOI：
10.1016/j.expneurol.2004.05.033
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发表时间：
2004-10-01
影响因子：
5.3
通讯作者：
Xu, XM
中科院分区：
文献类型：
--
作者：
Iannotti, C;Zhang, YP;Xu, XM
本研究探讨了胶质细胞源性神经营养因子（GDNF），转化生长因子-β（TGF-β）超家族的远亲成员，在成年大鼠中度挫伤性脊髓损伤（SCI）后的神经保护作用。使用Infinite Horizon撞击器（IH;撞击力= 150 kDyn）和两种浓度的重组人GDNF（rhGDNF; 1或5 μ g/穆尔）或盐水载体，使用Alzet微渗透泵鞘内递送28天，造成T11脊髓挫伤。我们证明，在伤后7周，GDNF输注显著减少了34-42%的总病变体积（体视学评估），并增加了10-13%的白色物质保留的百分比（在损伤震中测量），与载体输注相比。逆行追踪显示，GDNF输注导致在propriospinal区域以及在两个脊髓上区域，即延髓和脑桥网状结构，和外侧前庭核的FluoroGold（FG）标记的神经元的数量显着增加。免疫荧光染色证实，备用的白色物质含有神经递质阳性轴突。然而，经颅磁运动诱发电位（tcMMEP）评估显示GDNF和溶剂注入组之间的发作潜伏期和振幅没有显着差异。这些结果表明，GDNF对损伤后白色物质的保留和固有和脊髓上轴突子集的保留具有强烈的神经保护作用。然而，tcMMEP的恢复需要在白色物质的限定区域中保留和/或髓鞘形成轴突，该区域在该损伤严重程度水平下不是保留的就是髓鞘再生的。(C)2004年爱思唯尔公司All rights reserved.
The present study investigated neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF), a distant member of the transforming growth factor-beta (TGF-beta) superfamily, following moderate contusive spinal cord injury (SCI) in adult rats. A T11 spinal cord contusion injury was made using an Infinite Horizon impactor (IH; impact force = 150 kDyn) and recombinant human GDNF at two concentrations (rhGDNF; 1 or 5 mug/mul), or saline vehicle was delivered intrathecally for 28 days using an Alzet miniosmotic pump. We demonstrated that, at 7 weeks postinjury, GDNF infusion significantly reduced the total lesion volume by 34-42% (assessed stereologically) and increased the percentage of white matter sparing by 10-13% (measured at the injury epicenter), as compared to the vehicle infusion. Retrograde tracing revealed that GDNF infusion resulted in a significant increase in the number of FluoroGold (FG)-labeled neurons in propriospinal regions as well as in two supraspinal regions, that is, the medullary and pontine reticular formation, and the lateral vestibular nucleus. Immunofluorescent staining confirmed that the spared white matter contained neurofilament-positive axons. However, transcranial magnetic motor-evoked potential (tcMMEP) assessment revealed no significant difference in onset latency and amplitude between the GDNF- and vehicle-infused groups. These results suggest that GDNF has a strong neuroprotective effect on white matter sparing and the sparing of a subset of proprio- and supraspinal axons following injury. However, a return of tcMMEPs requires the sparing and/or myelination of axons in a defined region of the white matter which was either not spared or remyelinated at this level of injury severity. (C) 2004 Elsevier Inc. All rights reserved.