BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats
BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats
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DOI：
10.1093/brain/awl087
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发表时间：
2006-06-01
期刊：
影响因子：
14.5
通讯作者：
Fouad, K.
中科院分区：
文献类型：
--
作者：
Vavrek, R.;Girgis, J.;Fouad, K.
虽然损伤轴突的再生在成年中枢神经系统内受到抑制，但在不完全脊髓损伤（SCI）的患者和动物中可以发现中度恢复。这可以部分归因于发芽的备用和受伤的轴突，喙和尾侧的病变，分别。最近，据报道，胸部脊髓损伤后，这种发芽可以导致损伤的轴突通过propriospinal interneurons（PrI）与尾部目标的间接重新连接。在这里，我们试图通过将神经营养因子BDNF（脑源性神经营养因子），在受损的皮质脊髓神经元或NT-3的细胞体附近，鞘内注射到颈脊髓，进一步促进这种自发修复机制。我们在胸脊髓进行了背侧半切，只保留了左腹外侧象限。这种类型的病变并没有促进发芽受伤的皮质脊髓轴突或重新路由通过连合PrI。另外，在颈膨大处接受NT-3的大鼠中，没有发现发芽增加，但是在受损皮质脊髓神经元的细胞体处接受BDNF的动物显示出侧支发芽和与PrI接触的数量显著增加。当BDNF被给予未损伤的动物时，没有观察到这一点。虽然两组之间在水平阶梯行走方面没有统计学差异，但侧支发芽和接触次数的增加与功能恢复相关。因此，细胞体治疗可以促进受损CNS的可塑性，并且可能是与局部再生促进策略结合的有价值的治疗方法。
Although regeneration of injured axons is inhibited within the adult CNS, moderate recovery can be found in patients and animals with incomplete spinal cord injury (SCI). This can be partly attributed to sprouting of spared and injured axons, rostral and caudal to the lesion, respectively. Recently, it has been reported that following a thoracic SCI such sprouting can result in indirect reconnections of the lesioned axons to caudal targets via propriospinal interneurons (PrI). Here, we attempted to further promote this spontaneous repair mechanism by applying the neurotrophic factor BDNF (brain-derived neurotrophic factor), in the vicinity of the cell bodies of lesioned corticospinal neurons or NT-3, intrathecally to the cervical spinal cord. We performed a dorsal over-hemisection at the thoracic spinal cord sparing only the left ventrolateral quadrant. This type of lesion did not promote sprouting of injured corticospinal axons or re-routing via commissural PrI. Also, in rats that received NT-3 at the cervical enlargement, no increase in sprouting was found. However, animals receiving BDNF at the cell bodies of lesioned corticospinal neurons showed a significant increase in collateral sprouting and in the number of contacts with PrI. This was not observed when BDNF was administered to unlesioned animals. Although no statistical difference in the horizontal ladder walking was found between the groups, the increase in collateral sprouting and in the number of contacts correlated with the functional recovery. Hence, cell body treatment can promote plasticity of the injured CNS and may be a valuable treatment approach in conjunction with local regeneration promoting strategies.