MK-801 prevents hippocampal neurodegeneration in neonatal hypoxic-ischemic rats
L. M. Ford, P. R. Sanberg, A. B. Norman and M. H. Fogelson
Department of Pediatric Neurology, Children's Hospital Medical Center, Cincinnati, OH 45229.
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.
