Kasahara Kazuma, Nakagawa Takao, Kubota Toshihiko
Department of Neurosurgery, University of Fukui, Fukui, Japan.
Spine (Phila Pa 1976). 2006 Aug 15;31(18):2059-66. doi: 10.1097/01.brs.0000231893.21964.f2.
An experimental animal study about neuronal loss and the expression of neurotrophic factors in the chronic compressive spinal cords.
To investigate neuronal loss and the expression of neurotrophic factors in the chronic compressive spinal cords of rats, and to evaluate effects of decompressive procedures for the neuronal loss.
Chronic compression of spinal cords induces the loss of motor neurons in the anterior horn. However, the precise mechanism of this neuronal loss is not still understood completely. Furthermore, it is uncertain whether decompressive procedures prevent this neuronal loss or not.
A thin expanding polymer sheet was implanted microsurgically underneath T7 laminae of rats. After 6, 9, 12, and 15 weeks, the thoracic spinal cord was harvested and examined histopathologically. The expression of neurotrophic factors, including NGF, BDNF, NT-3, GDNF, CNTF, and VEGF, was analyzed using semiquantitative RT-PCR, enzyme immunoassay, and immunohistochemistry. Decompressive surgery was performed through the removal of T7 laminae and the compression materials 6, 9, and 12 weeks after starting compression. Three weeks later, respectively, the neuronal loss in the anterior horn was estimated.
The spinal cords were progressively flattened by the expanding of the implanted polymer sheet, and the number of motor neurons in the anterior horn decreased, especially from 6 to 9 weeks after starting compression. Semiquantitative RT-PCR analysis showed that the expression of NGF and BDNF mRNAs was decreased significantly in the spinal cords of 12-week compression group compared with the 6-week compression group and that NGF mRNA expression was up-regulated significantly in the 6-week compression group relative to the 6-week control group. Any changes of expression of other neurotrophic factors were not significant. Since BDNF, not NGF, has been known to be one of the powerful survival factors for spinal motoneurons, we investigated the levels of BDNF protein in the compressive spinal cords using enzyme immunoassay and immunohistochemistry. We demonstrated the level of BDNF protein in the compressive spinal cords was increased 6 weeks after compression but declined after 12 weeks. The decompressive procedure in the 6 weeks after compression prevented neuronal loss, but the same procedure in the 9 or 12 weeks was ineffective.
From the point of view of neuronal loss, decompressive surgery at an earlier stage, when compensatory mechanisms including the up-regulation of BDNF might be still effective, could provide better therapeutic results against chronic mechanical compressive spinal cord lesions.
一项关于慢性压迫性脊髓中神经元丢失及神经营养因子表达的实验性动物研究。
研究大鼠慢性压迫性脊髓中神经元丢失及神经营养因子的表达，并评估减压手术对神经元丢失的影响。
脊髓慢性压迫会导致前角运动神经元丢失。然而，这种神经元丢失的确切机制仍未完全明了。此外，减压手术能否预防这种神经元丢失也不确定。
通过显微手术将一片薄的膨胀聚合物片植入大鼠T7椎板下方。在6、9、12和15周后，取出胸段脊髓并进行组织病理学检查。使用半定量逆转录聚合酶链反应、酶免疫测定和免疫组织化学分析神经营养因子（包括神经生长因子、脑源性神经营养因子、神经营养素-3、胶质细胞源性神经营养因子、睫状神经营养因子和血管内皮生长因子）的表达。在开始压迫6、9和12周后，通过切除T7椎板和压迫材料进行减压手术。分别在三周后评估前角的神经元丢失情况。
随着植入聚合物片的膨胀，脊髓逐渐变平，前角运动神经元数量减少，尤其是在开始压迫后的6至9周。半定量逆转录聚合酶链反应分析显示，与6周压迫组相比，12周压迫组脊髓中神经生长因子和脑源性神经营养因子mRNA的表达显著降低，且相对于6周对照组，6周压迫组神经生长因子mRNA表达显著上调。其他神经营养因子表达的任何变化均不显著。由于已知脑源性神经营养因子而非神经生长因子是脊髓运动神经元强大的存活因子之一，我们使用酶免疫测定和免疫组织化学研究了压迫性脊髓中脑源性神经营养因子蛋白的水平。我们发现压迫性脊髓中脑源性神经营养因子蛋白水平在压迫6周后升高，但在12周后下降。压迫6周后的减压手术可预防神经元丢失，但在9周或12周进行相同手术则无效。
从神经元丢失的角度来看，在包括脑源性神经营养因子上调等代偿机制可能仍然有效的早期阶段进行减压手术，可能会为慢性机械性压迫性脊髓损伤提供更好的治疗效果。
