Ito Toshinori, Ohtori Seiji, Hata Katsuhiko, Inoue Gen, Moriya Hideshige, Takahashi Kazuhisa, Yamashita Toshihide
Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Spine (Phila Pa 1976). 2007 Sep 1;32(19):2070-5. doi: 10.1097/BRS.0b013e318145a502.
Immunohistochemical and behavioral study using a rat cauda equina compression model.
To investigate, after cauda equina compression by spinal canal stenosis (SCS), Rho activation in the spinal cord and cauda equina, and the effect of intrathecal administration of a Rho kinase inhibitor on hypoalgesia and motor dysfunction.
Compression of the cauda equina caused by SCS is a common clinical disorder associated with sensory disturbance and intermittent claudication. Cauda equina compression is thought to reduce blood flow and result in nerve degeneration caused by various cytokines. Rho, a member of the small GTPases, is a signal transmitter. It promotes Wallerian degeneration, decreases blood flow in the spinal cord and brain, and increases expression of several cytokines. Currently, Rho kinase inhibitor is used clinically to treat progressive nerve damage due to cerebrovascular disorders. However, its effect for SCS has not been evaluated.
Forty-two 6-week-old male Sprague-Dawley rats (200-250 g) were used. For the SCS model (n = 27), a small piece of silicon was placed under the lamina of the fourth lumbar vertebra. In the sham-operated group, laminectomies were performed at L5 only (n = 15). We examined mechanical sensitivity and motor function using von Frey hairs and a treadmill, and immunohistochemically localized Rho in the spinal ventral neurons, axons, and Schwann cells in the cauda equina. We also examined the effects of intrathecally administered Rho kinase inhibitor for hypoalgesia or motor dysfunction caused by SCS.
We observed motor dysfunction and hypoalgesia and activated Rho-immunoreactive cells in spinal ventral neuroreported to induce neurite and axonal outgrowth in the spinal cord and brain after nervous system injury. In addition, 1 report showed that Rho kinase was involved in Wallerian degeneration that was rescued by Rho kinase inhibitor. Furthermore, it is thought that Rho is involved in TNF-alpha and interleukin (IL) production in the central nervous system, and the production was inhibited by administering Rho kinase inhibitor in the central nervous system. Regardns, axons, and Schwann cells in the cauda equina. Intrathecal administration of Rho kinase inhibitor improved mechanical hypoalgesia and motor dysfunction caused by SCS.
Activated Rho may play an important role in nerve damage in the cauda equina in SCS. Rho kinase inhibitor may be a useful tool in determining the pathomechanism of cauda equina syndrome caused by SCS.
使用大鼠马尾神经压迫模型进行免疫组织化学和行为学研究。
研究椎管狭窄（SCS）导致马尾神经受压后，脊髓和马尾神经中Rho的激活情况，以及鞘内注射Rho激酶抑制剂对痛觉减退和运动功能障碍的影响。
SCS导致的马尾神经受压是一种常见的临床疾病，与感觉障碍和间歇性跛行有关。马尾神经受压被认为会减少血流，并导致由各种细胞因子引起的神经变性。Rho是小GTP酶家族的成员，是一种信号转导分子。它促进沃勒变性，减少脊髓和大脑中的血流，并增加几种细胞因子的表达。目前，Rho激酶抑制剂在临床上用于治疗脑血管疾病导致的进行性神经损伤。然而，其对SCS的作用尚未得到评估。
使用42只6周龄雄性Sprague-Dawley大鼠（200-250克）。对于SCS模型（n = 27），在第四腰椎椎板下放置一小片硅片。在假手术组中，仅在L5进行椎板切除术（n = 15）。我们使用von Frey毛发和跑步机检查机械敏感性和运动功能，并通过免疫组织化学方法在脊髓腹侧神经元、轴突和马尾神经中的施万细胞中定位Rho。我们还研究了鞘内注射Rho激酶抑制剂对SCS引起的痛觉减退或运动功能障碍的影响。
我们观察到运动功能障碍和痛觉减退，并在脊髓腹侧神经元、轴突和马尾神经中的施万细胞中观察到Rho免疫反应性细胞的激活。鞘内注射Rho激酶抑制剂改善了SCS引起的机械性痛觉减退和运动功能障碍。
激活的Rho可能在SCS中马尾神经损伤中起重要作用。Rho激酶抑制剂可能是确定SCS引起的马尾神经综合征发病机制的有用工具。
