Agrawal S K, Theriault E, Fehlings M G
Division of Neurosurgery, University of Toronto, and Toronto Hospital Research Institute, Ontario, Canada.
J Neurotrauma. 1998 Nov;15(11):929-41. doi: 10.1089/neu.1998.15.929.
Metabotropic glutamate receptors (mGluRs) participate in glutamate neural transmission, but their role in the pathophysiology of spinal cord injury (SCI) has not been explored. Accordingly, we examined the role of group I mGluRs, which are linked to phospholipase C, in mediating SCI using an in vitro model. A dorsal column segment was isolated from the spinal cord of adult rats, maintained in vitro, and injured by compression for 15 sec with a clip having a 2 g closing force. Under control conditions after SCI, the compound action potential (CAP) amplitude was reduced to 69.1 +/- 5.4% of baseline. Blockade of group I mGluR receptors with MCPG, 4CPG, or AIDA resulted in improved recovery of CAP amplitude (82.2 +/- 2.0%, 86.2 +/- 3.9%, and 86.0 +/- 2.5% of baseline, respectively). The group I/II agonist trans-ACPD and selective group I agonist DHPG exacerbated the posttraumatic reduction of CAP amplitude. The phospholipase C inhibitor U-73122 improved recovery of CAP amplitude after traumatic spinal cord axonal injury. Western blotting and immunocytochemistry demonstrated the presence of mGluR1alpha-immunopositive astrocytes and the absence of mGluR5 in spinal cord white matter. These studies are consistent with the hypothesis that activation of group I mGluR receptors after SCI exacerbates posttraumatic axonal injury through a phospholipase C dependent mechanism. The presence of mGluR1alpha labeling on astrocytes suggests a role for these cells in the pathophysiology of SCI. Additional studies in vivo, are required to further clarify the role of mGluRs in acute traumatic SCI.
代谢型谷氨酸受体（mGluRs）参与谷氨酸能神经传递，但其在脊髓损伤（SCI）病理生理学中的作用尚未得到探索。因此，我们使用体外模型研究了与磷脂酶C相关的I组mGluRs在介导SCI中的作用。从成年大鼠脊髓分离出背柱节段，在体外进行培养，并用具有2 g闭合力的夹子压迫15秒造成损伤。在SCI后的对照条件下，复合动作电位（CAP）幅度降低至基线的69.1±5.4%。用MCPG、4CPG或AIDA阻断I组mGluR受体会使CAP幅度恢复改善（分别为基线的82.2±2.0%、86.2±3.9%和86.0±2.5%）。I/II组激动剂反式-ACPD和选择性I组激动剂DHPG加剧了创伤后CAP幅度的降低。磷脂酶C抑制剂U-73122改善了创伤性脊髓轴突损伤后CAP幅度的恢复。蛋白质印迹法和免疫细胞化学显示脊髓白质中存在mGluR1α免疫阳性星形胶质细胞，而不存在mGluR5。这些研究与以下假设一致，即SCI后I组mGluR受体的激活通过磷脂酶C依赖性机制加剧创伤后轴突损伤。星形胶质细胞上mGluR1α标记的存在表明这些细胞在SCI病理生理学中发挥作用。需要进行更多的体内研究以进一步阐明mGluRs在急性创伤性SCI中的作用。
