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October 1989

MK-801 Prevents Hippocampal Neurodegeneration in Neonatal Hypoxic-Ischemic Rats

Author Affiliations

From the Department of Pediatric Neurology, Children's Hospital Medical Center, Cincinnati (Drs Ford and Fogelson), and the Laboratory of Neuroscience, Departments of Psychiatry, University of Cincinnati (Ohio) Medical Center (Drs Sanberg and Norman).

Arch Neurol. 1989;46(10):1090-1096. 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-dayold 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.