Ford L M, Sanberg P R, Norman A B, Fogelson M H
Department of Pediatric Neurology, Children's Hospital Medical Center, Cincinnati, OH 45229.
Arch Neurol. 1989 Oct;46(10):1090-6. doi: 10.1001/archneur.1989.00520460072016.
In cerebral asphyxia, enhanced postsynaptic stimulation of N-methyl-D-aspartate (NMDA) receptor by excessive glutamate may mediate neuronal injury and death. The neuroprotective potential of the novel, potent NMDA receptor antagonist MK-801 was assessed by evaluating hippocampal behavioral and histologic outcomes in an experimental rat model of neonatal hypoxia/ischemia. Seven-day-old rats with and without MK-801 pretreatment were subjected to unilateral carotid ligation followed by 2 hours of hypoxia. At age 30 days, spontaneous alternation behavior was measured using a conventional wooden T maze. Hypoxic-ischemic animals pretreated with saline demonstrated a significant impairment in spontaneous alternation behavior compared with that of normal control rats and the hypoxic-ischemic rats pretreated with MK-801. Hippocampal neuronal damage in the CA1 and CA3 regions was prevented in animals pretreated with MK-801 vs saline-treated controls. Therefore, while saline-treated rats with hippocampal lesions showed defective memory and hippocampal neuronal destruction, pretreatment with MK-801 protected rats. Thus, MK-801 appears to protect hippocampal neurons from hypoxia/ischemia and may be potentially beneficial in preventing neonatal asphyxial brain damage.
在脑性窒息中，过量谷氨酸对N-甲基-D-天冬氨酸（NMDA）受体的突触后刺激增强可能介导神经元损伤和死亡。通过评估新生大鼠缺氧/缺血实验模型中的海马行为和组织学结果，来评估新型强效NMDA受体拮抗剂MK-801的神经保护潜力。对7日龄大鼠进行单侧颈动脉结扎，随后缺氧2小时，其中部分大鼠在缺氧前给予MK-801预处理，部分大鼠未给予预处理。在30日龄时，使用传统的木制T迷宫测量自发交替行为。与正常对照大鼠以及给予MK-801预处理的缺氧缺血大鼠相比，给予生理盐水预处理的缺氧缺血动物在自发交替行为方面表现出显著受损。与给予生理盐水处理的对照组相比，给予MK-801预处理的动物中，CA1和CA3区域的海马神经元损伤得到了预防。因此，虽然有海马损伤的生理盐水处理大鼠表现出记忆缺陷和海马神经元破坏，但MK-801预处理可保护大鼠。因此，MK-801似乎可保护海马神经元免受缺氧/缺血影响，可能对预防新生儿窒息性脑损伤具有潜在益处。
