Blight A R, Leroy E C, Heyes M P
Division of Neurosurgery, University of North Carolina at Chapel Hill, 27599, USA.
J Neurotrauma. 1997 Feb;14(2):89-98. doi: 10.1089/neu.1997.14.89.
Experimental compression injury of the spinal cord in guinea pigs results in delayed neurologic deficits that continue to increase in severity for several days following trauma, coincident with inflammatory responses, including invasion of the lesion by mononuclear phagocytes and increased levels of the neurotoxin quinolinic acid (QUIN). Inflammatory responses and QUIN elevation also occur following spinal cord contusion in rats, but maximal neurologic deficits develop immediately. In this study, somatosensory evoked potentials (SEP) and tissue, serum, and cerebrospinal fluid levels of QUIN were measured in guinea pigs and rats following similar compression injuries of the thoracic spinal cord. SEP changes differed between the species, consistent with other neurological changes. In guinea pigs, increases in QUIN levels at the lesion site began at 1 day postinjury, achieved maximal elevation (100-fold) by 12 days, then declined, but remained above serum levels at 25 days postinjury. A similar increase occurred in adjacent areas of the spinal cord, with lower peak levels. In rats, tissue QUIN at the center of the lesion remained below serum levels at all times, increasing moderately (<10-fold) up to 7 days, then decreasing between 7 and 25 days. These data demonstrate differences in the time course and magnitude of QUIN accumulation and neurological deficit between guinea pig and rat, which may relate to differences in secondary pathological mechanisms. Such profound differences may affect the use of these species for evaluation of experimental therapy in this and other inflammatory conditions of the central nervous system.
豚鼠脊髓实验性压迫损伤会导致延迟性神经功能缺损，创伤后数天内其严重程度持续增加，这与炎症反应同时发生，包括单核吞噬细胞侵入损伤部位以及神经毒素喹啉酸（QUIN）水平升高。大鼠脊髓挫伤后也会出现炎症反应和QUIN升高，但最大神经功能缺损立即出现。在本研究中，对豚鼠和大鼠进行类似的胸段脊髓压迫损伤后，测量了体感诱发电位（SEP）以及组织、血清和脑脊液中的QUIN水平。SEP变化在不同物种间存在差异，这与其他神经学变化一致。在豚鼠中，损伤部位的QUIN水平在损伤后1天开始升高，到12天时达到最大升高幅度（100倍），然后下降，但在损伤后25天时仍高于血清水平。脊髓相邻区域也出现了类似的升高，但峰值水平较低。在大鼠中，损伤中心部位的组织QUIN始终低于血清水平，在7天内适度升高（<10倍），然后在7至25天之间下降。这些数据表明豚鼠和大鼠在QUIN积累的时间进程和幅度以及神经功能缺损方面存在差异，这可能与继发性病理机制的差异有关。如此显著的差异可能会影响在评估针对这种及其他中枢神经系统炎症性疾病的实验性治疗中对这些物种的使用。
