Kuroda Y, Fujisawa H, Strebel S, Graham D I, Bullock R
Department of Neurosurgery, Institute of Neurological Sciences, Glasgow, Scotland.
Neurosurgery. 1994 Jul;35(1):106-12. doi: 10.1227/00006123-199407000-00016.
Glutamate antagonists are the most powerful neuroprotective drugs in laboratory studies of focal cerebral ischemia. Because the majority of clinical conditions in which focal brain ischemia occurs are associated with high intracranial pressure (ICP), we have used the rat acute subdural hematoma model to evaluate the effects of three glutamate N-methyl-D-aspartate antagonists, MK-801, CGS 19755 (SELFOTEL), D-CPP-ene, and mannitol, upon ICP and also upon the volume of ischemic brain damage. Only mannitol produced a significant reduction in ICP and improved cerebral perfusion pressure. The three glutamate antagonists did not significantly affect ICP or cerebral perfusion pressure, but they were associated with a significantly smaller zone of focal brain damage, when compared to the mannitol and saline groups. N-methyl-D-aspartate antagonists do not increase ICP or jeopardize cerebral perfusion pressure when administered under anesthesia with a controlled PaCO2 level. Further studies in humans are indicated.
在局灶性脑缺血的实验室研究中，谷氨酸拮抗剂是最有效的神经保护药物。由于大多数发生局灶性脑缺血的临床情况都与高颅内压（ICP）相关，我们使用大鼠急性硬膜下血肿模型来评估三种谷氨酸N-甲基-D-天冬氨酸拮抗剂（MK-801、CGS 19755（SELFOTEL）、D-CPP-ene）以及甘露醇对颅内压和缺血性脑损伤体积的影响。只有甘露醇能显著降低颅内压并改善脑灌注压。与甘露醇组和生理盐水组相比，这三种谷氨酸拮抗剂对颅内压或脑灌注压没有显著影响，但它们与明显更小的局灶性脑损伤区域相关。在麻醉状态下，当控制PaCO2水平时，N-甲基-D-天冬氨酸拮抗剂不会增加颅内压或危及脑灌注压。有必要在人体中进行进一步研究。
