Chen M H, Bullock R, Graham D I, Miller J D, McCulloch J
Institute of Neurological Sciences, University of Glasgow, Scotland.
J Neurosurg. 1991 Jun;74(6):944-50. doi: 10.3171/jns.1991.74.6.0944.
The ability of a competitive N-methyl-D-aspartate (NMDA) receptor antagonist (D-CPP-ene) to reduce irreversible brain damage has been examined in a rodent model of acute subdural hematoma. Acute subdural hematoma was produced by the slow injection of 400 microliters homologous blood into the subdural space overlying the parietal cortex in halothane-anesthetized rats. Brain damage was assessed histologically in sections at multiple coronal planes in animals sacrificed 4 hours after induction of the subdural hematoma. Pretreatment with D-CPP-ene (15 mg/kg) significantly reduced the volume of ischemic brain damage produced by the subdural hematoma from 62 +/- 8 cu mm (mean +/- standard error of the mean) in vehicle-treated control rats to 29 +/- 7 cu mm in drug-treated animals. These data demonstrate the anti-ischemic efficacy of NMDA antagonists in an animal model of intracranial hemorrhage in which intracranial pressure is elevated, and suggest that excitotoxic mechanisms (which are susceptible to antagonism by D-CPP-ene) may play a role in the ischemic brain damage which is observed in patients who die after acute subdural hematoma.
在急性硬膜下血肿的啮齿动物模型中，研究了竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂（D-CPP-ene）减轻不可逆脑损伤的能力。通过在氟烷麻醉的大鼠顶叶皮质上方的硬膜下间隙缓慢注射400微升同源血液来制造急性硬膜下血肿。在硬膜下血肿形成后4小时处死动物，对多个冠状平面的切片进行组织学评估脑损伤情况。用D-CPP-ene（15毫克/千克）预处理可使硬膜下血肿所致的缺血性脑损伤体积从溶剂处理的对照大鼠中的62±8立方毫米（平均值±平均标准误差）显著减少至药物处理动物中的29±7立方毫米。这些数据证明了NMDA拮抗剂在颅内压升高的颅内出血动物模型中的抗缺血功效，并表明兴奋性毒性机制（易受D-CPP-ene拮抗）可能在急性硬膜下血肿后死亡患者中观察到的缺血性脑损伤中起作用。
