Jacobs T P, Shohami E, Baze W, Burgard E, Gunderson C, Hallenbeck J, Feuerstein G
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Cent Nerv Syst Trauma. 1987;4(2):95-118. doi: 10.1089/cns.1987.4.95.
Eicosanoids are known mediators of inflammation, vascular permeability, and are involved in microcirculatory blood flow regulation. To study their potential involvement in the pathophysiology of CNS trauma we used a rabbit spinal cord trauma model. Rabbits were subjected to lumbar spinal cord trauma produced by a modification of the Allen weight-drop method. TXB2, 6-keto-PGF1 alpha, PGE2, and 5-hydroxyeicosatetraenoic acid (5-HETE) release from spinal cord slices incubated ex vivo were measured by radioimmunoassay at 5, 30 min, 24 hrs, and 2 wks after trauma. Five and 30 min after trauma the TXB2/6-keto-PGF1 alpha ratio was elevated and the release of 5-HETE at 5 min after trauma increased in the injured spinal cord whereas release of 6-keto-PGF1 alpha and PGE2 remained at base-line levels. In the thoracic spinal cord, TXB2 and 6-keto-PGF1 alpha release were increased at 30 min after trauma. Release of 5-HETE from the injured spinal cord was also elevated 24 hrs after trauma. Two wks after trauma, TXB2 and 6-keto-PGF1 alpha release were also elevated in the injured spinal cord. Measurements of tissue water content by microgravimetry indicated progressive edema in the injury site while histopathological evaluation indicated progressive damage and tissue destruction. The results of this study suggest that eicosanoids may be involved in the pathophysiology of spinal cord trauma through two potential mechanisms: 1) site specific increase in the TXB2/6-keto-PGF1 alpha ratio immediately following trauma which is due primarily to an increase in TXA2 synthesis; 2) the increase synthesis of 5-HETE which signals the activation of the 5-lipoxygenase pathway of arachidonate metabolism and production of mediators that are involved in inflammatory mechanisms and may affect local blood flow regulation and blood-spinal cord barrier integrity.
类二十烷酸是已知的炎症、血管通透性介质，并参与微循环血流调节。为研究它们在中枢神经系统创伤病理生理学中的潜在作用，我们使用了兔脊髓创伤模型。通过改良的艾伦重物坠落法对兔子造成腰段脊髓创伤。在创伤后5分钟、30分钟、24小时和2周，通过放射免疫分析法测量离体培养的脊髓切片中TXB2、6-酮-前列环素F1α、前列腺素E2和5-羟基二十碳四烯酸（5-HETE）的释放。创伤后5分钟和30分钟，损伤脊髓中TXB2/6-酮-前列环素F1α比值升高，创伤后5分钟5-HETE的释放增加，而6-酮-前列环素F1α和前列腺素E2的释放保持在基线水平。在胸段脊髓，创伤后30分钟TXB2和6-酮-前列环素F1α的释放增加。创伤后24小时，损伤脊髓中5-HETE的释放也升高。创伤后2周，损伤脊髓中TXB2和6-酮-前列环素F1α的释放也升高。微量重力法测量组织含水量表明损伤部位水肿进行性加重，而组织病理学评估表明损伤进行性加重和组织破坏。本研究结果表明，类二十烷酸可能通过两种潜在机制参与脊髓创伤的病理生理学：1）创伤后立即出现TXB2/6-酮-前列环素F1α比值的部位特异性增加，这主要是由于血栓素A2合成增加；2）5-HETE合成增加，这表明花生四烯酸代谢的5-脂氧合酶途径被激活，并产生参与炎症机制的介质，可能影响局部血流调节和血脊髓屏障完整性。
