Mills Charles D, Johnson Kathia M, Hulsebosch Claire E
Department of Anatomy and Neurosciences, University of Texas Medical Branch at Galveston, 77555-1043, USA.
J Neurotrauma. 2002 Jan;19(1):23-42. doi: 10.1089/089771502753460213.
Spinal cord injury (SCI) initiates a cascade of biochemical events that leads to an increase in extracellular excitatory amino acid (EAA) concentrations, which results in glutamate receptor-mediated excitotoxic events. An important division of these glutamate receptors is the metabotropic glutamate receptor (mGluR) class, which is divided into three groups. Of these three groups, group I (mGluR1 and mGluR5) activation can initiate a number of intracellular pathways that lead to increased extracellular EAA concentrations. To evaluate subtypes of group I mGluRs in SCI, we administered AIDA (group I antagonist), LY 367385 (mGluR1 specific antagonist), or MPEP (mGluR5 specific antagonist) by interspinal injection to adult male Sprague-Dawley rats (175-200 g) immediately following injury at T10 with an NYU impactor (12.5-mm drop, 10-g rod, 2 mm in diameter). AIDA- and LY 367385-treated subjects had improved locomotor scores and demonstrated an attenuation in the development of mechanical allodynia as measured by von Frey stimulation of the forelimbs; however, LY 367385 potentiated the development of thermal hyperalgesia. MPEP had no effect on locomotor recovery or mechanical allodynia, but attenuated the development of thermal hyperalgesia. AIDA and LY 367385 treatment resulted in a significant increase in tissue sparing compared to the vehicle-treated group at 4 weeks following SCI. These results suggest that mGluRs play an important role in EAA toxicity and have different acute pathophysiological roles following spinal cord injury.
脊髓损伤（SCI）引发一系列生化事件，导致细胞外兴奋性氨基酸（EAA）浓度升高，进而引发谷氨酸受体介导的兴奋性毒性事件。这些谷氨酸受体的一个重要分类是代谢型谷氨酸受体（mGluR）类别，它分为三组。在这三组中，I组（mGluR1和mGluR5）的激活可启动一些细胞内信号通路，导致细胞外EAA浓度升高。为了评估脊髓损伤中I组mGluR的亚型，我们在成年雄性Sprague-Dawley大鼠（175 - 200 g）T10节段用NYU撞击器（12.5毫米落差，10克撞杆，直径2毫米）损伤后立即通过脊髓内注射给予AIDA（I组拮抗剂）、LY 367385（mGluR1特异性拮抗剂）或MPEP（mGluR5特异性拮抗剂）。接受AIDA和LY 367385治疗的大鼠运动评分有所改善，并且通过对前肢进行von Frey刺激测量显示机械性异常性疼痛的发展有所减轻；然而，LY 367385增强了热痛觉过敏的发展。MPEP对运动恢复或机械性异常性疼痛没有影响，但减轻了热痛觉过敏的发展。与脊髓损伤后4周接受赋形剂治疗的组相比，AIDA和LY 367385治疗导致组织保留显著增加。这些结果表明，mGluR在EAA毒性中起重要作用，并且在脊髓损伤后具有不同的急性病理生理作用。
