MK-801 prevents hypobaric-ischemic neuronal degeneration in infant rat brain.
Recent evidence implicates the endogenous excitatory amino acids, glutamate (Glu) and aspartate, in hypoxic/ischemic neuronal degeneration. In a preceding article (Ikonomidou et al., 1989) we described a new model for studying hypoxic/ischemic neuronal degeneration in the infant rat brain that entails unilateral common carotid artery ligation followed by exposure to a partial vacuum for 75 min. Promising features of this model include a low mortality rate and high incidence of acute brain damage disseminated over numerous brain regions. In addition, there is a striking similarity between the type of cytopathology characterizing this model of hypoxic/ischemic neuronal degeneration and that which has been described in infant animals treated with Glu. MK-801 is a powerful antagonist of the N-methyl-D-aspartate (NMDA) receptor ionophore complex (a subtype of Glu receptor). In the present study, after unilateral carotid artery ligation was performed on 10-d-old rat pups, they were treated either with MK-801 (1 mg/kg i.p.) or saline 15 min before exposure to the hypobaric condition. MK-801 exerted a strong neuroprotective effect without serious side effects; the majority of saline control animals sustained severe brain damage, whereas the majority of MK-801-treated pups had no brain damage. These and other recent findings suggest that the NMDA receptor may play an important role in hypoxic/ischemic neuronal degeneration in the immature brain and provide hope that NMDA antagonists such as MK-801 may be effective in preventing such degeneration.
Olney
J W
JW
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110.
Ikonomidou
C
C
Mosinger
J L
JL
Frierdich
G
G
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001274:Atmospheric Pressure; D001831:Body Temperature; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D005260:Female; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D009474:Neurons / Q000473:pathology*; D051381:Rats
D003986:Dibenzocycloheptenes; D016291:Dizocilpine Maleate