Jacobs T P, Shohami E, Baze W, Burgard E, Gunderson C, Hallenbeck J M, Feuerstein G
Stroke. 1987 Jul-Aug;18(4):741-50. doi: 10.1161/01.str.18.4.741.
Secondary motor dysfunction is often observed following ischemic episodes in the central nervous system. To study potential mechanisms of postischemic motor deterioration, we developed a rabbit spinal cord ischemia model that has characteristics similar to the clinical condition termed deteriorating stroke. In this model, 70% of the rabbits regained substantial motor function by 4 hours after complete hindlimb paralysis during lumbar spinal cord ischemia; however, over the next 20 hours motor function steadily declined to the point where only 30% of the rabbits had minimal hopping function. The role of eicosanoids in spinal cord ischemia was studied by radioimmunoassay of several prostaglandins (6-keto-PGF1 alpha, PGE2, and TxB2) in the spinal cord. After 5 minutes of reperfusion, TxB2 levels were markedly elevated (p less than 0.05) while 6-keto-PGF1 alpha levels did not change. The TxB2:6-keto-PGF1 alpha ratio was also significantly increased. After 30 minutes of reperfusion, PGE2 levels were also elevated (p less than 0.05). Tissue edema measured by microgravimetry was also increased after 30 minutes of reperfusion in both gray and white matter. By 4 hours of reperfusion, rabbits regained near-normal hindlimb motor function while PGE2, 6-keto-PGF1 alpha, TxB2, and tissue water content were back to normal. However, by 18 hours of reperfusion, when hindlimb function was deteriorating, TxB2 levels were elevated again, and edema in gray and white matter was increased as was the number of necrotic neurons observed by light microscopy. These results suggest that the secondary deterioration of motor neurologic function was due to the excess formation of TxA2 primarily in the late reperfusion phase. However, further studies are necessary to elucidate the relation of TxA2 with ischemic neural injury.
中枢神经系统缺血发作后常观察到继发性运动功能障碍。为研究缺血后运动功能恶化的潜在机制，我们建立了一种兔脊髓缺血模型，其特征与临床上称为恶化性中风的情况相似。在该模型中，70%的兔子在腰段脊髓缺血导致后肢完全麻痹后4小时恢复了相当程度的运动功能；然而，在接下来的20小时内，运动功能持续下降，到仅30%的兔子具有最小跳跃功能的程度。通过对脊髓中几种前列腺素（6-酮-前列腺素F1α、前列腺素E2和血栓素B2）进行放射免疫测定，研究了类花生酸在脊髓缺血中的作用。再灌注5分钟后，血栓素B2水平显著升高（p<0.05），而6-酮-前列腺素F1α水平未改变。血栓素B2与6-酮-前列腺素F1α的比值也显著增加。再灌注30分钟后，前列腺素E2水平也升高（p<0.05）。再灌注30分钟后，通过微量重力测定法测量的组织水肿在灰质和白质中均增加。到再灌注4小时时，兔子后肢运动功能恢复到接近正常，而前列腺素E2、6-酮-前列腺素F1α、血栓素B2和组织含水量均恢复正常。然而，到再灌注18小时时，当后肢功能恶化时，血栓素B2水平再次升高，灰质和白质中的水肿增加，光镜下观察到的坏死神经元数量也增加。这些结果表明，运动神经功能的继发性恶化主要是由于血栓素A2在再灌注后期过量形成。然而，需要进一步研究以阐明血栓素A2与缺血性神经损伤的关系。
