Shapira Y, Yadid G, Cotev S, Niska A, Shohami E
Intensive Care Unit (Department of Anesthesiology), Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
J Neurotrauma. 1990 Fall;7(3):131-9. doi: 10.1089/neu.1990.7.131.
The effect of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK801, was studied in a model of closed head injury in rats. Head trauma (HT) was induced over the left cerebral hemisphere by a calibrated weight-drop device. One or 3 h later, MK801 in saline was given i.p. in a single bolus of either 1, 3, or 10 mg/kg. The rats were killed at 4, 24, or 48 h after HT. Cortical tissue samples were taken from the injured zone and from the corresponding region of the contralateral hemisphere and analyzed for specific gravity (SG) by linear gradient columns. The neurological status of the traumatized rats was evaluated by a neurological severity score (NSS) 1 h after trauma and just before death. Pathological evaluation, based on size and severity of the lesion, was performed 24 and 48 h after HT on control and MK801-treated rats. A dose of 3 mg/kg MK801 given 1 h after trauma effectively prevented the reduction in tissue SG only at 24 h. The NSS could not be evaluated at 24 h after trauma because of the sedating effect of the drug. At 48 h posttrauma, however, the drug significantly improved the neurological state of the rats. No significant difference was found in the pathological score between treated and untreated rats. The results demonstrate neuroprotective properties of MK801, as expressed in two different variables--reduced edema formation and improved neurological recovery after HT. These findings support existing evidence that pharmacological intervention with NMDA receptor antagonist after head injury may be of clinical value in the management of head-injured patients.
在大鼠闭合性颅脑损伤模型中研究了非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂MK801的作用。通过校准的重物下落装置在大鼠左脑半球诱发头部创伤（HT）。1或3小时后，将MK801溶于生理盐水中，以1、3或10mg/kg的单次剂量腹腔注射。在HT后4、24或48小时处死大鼠。从损伤区域和对侧半球的相应区域采集皮质组织样本，通过线性梯度柱分析比重（SG）。在创伤后1小时和即将死亡前，通过神经严重程度评分（NSS）评估受创伤大鼠的神经状态。在HT后24和48小时，对对照组和MK801处理组的大鼠进行基于损伤大小和严重程度的病理评估。创伤后1小时给予3mg/kg的MK801仅在24小时时有效防止了组织SG的降低。由于药物的镇静作用，在创伤后24小时无法评估NSS。然而，在创伤后48小时，该药物显著改善了大鼠的神经状态。在治疗组和未治疗组大鼠之间的病理评分未发现显著差异。结果表明MK801具有神经保护特性，表现为两个不同的变量——减少水肿形成和改善HT后的神经恢复。这些发现支持了现有证据，即头部损伤后用NMDA受体拮抗剂进行药物干预可能对颅脑损伤患者的治疗具有临床价值。
