MK-801 PREVENTS HIPPOCAMPAL NEURODEGENERATION IN NEONATAL HYPOXIC-ISCHEMIC RATS
MK-801 PREVENTS HIPPOCAMPAL NEURODEGENERATION IN NEONATAL HYPOXIC-ISCHEMIC RATS
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DOI：
10.1001/archneur.1989.00520460072016
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发表时间：
1989-10-01
影响因子：
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通讯作者：
FOGELSON, MH
中科院分区：
文献类型：
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作者：
FORD, LM;SANBERG, PR;FOGELSON, MH
脑窒息时，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。通过评估新生儿缺氧/缺血实验大鼠模型中海马行为和组织学结果，评估新型强效NMDA受体拮抗剂MK-801的神经保护潜力。对给予和未给予MK-801预处理的7日龄大鼠进行单侧颈动脉结扎，然后缺氧2小时。在30日龄时，使用常规木制T迷宫测量自发交替行为。与正常对照组和MK-801预处理的缺氧缺血大鼠相比，生理盐水预处理的缺氧缺血动物的自发交替行为明显受损。MK-801预处理动物与生理盐水处理对照动物相比，可预防CA 1和CA 3区域的海马神经元损伤。因此，虽然生理盐水处理的海马损伤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似乎可以保护海马神经元免受缺氧/缺血，并可能有助于预防新生儿窒息性脑损伤。
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 CA 1 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.