MK-801 does not protect against hypoxic-ischemic brain injury in piglets.
OBJECTIVE
The excitatory amino acid inhibitor MK-801 has been shown in many animals species to protect against hypoxic-ischemic brain injury. We sought to determine whether hypoxic-ischemic injury to the newborn pig's brain could be prevented by the use of MK-801.


METHODS
Hypoxic-ischemic injury to the brain was induced in forty 0-3-day-old piglets. They were randomized to receive either 3 mg/kg MK-801 (MK-801 group, n = 20) or vehicle (control group, n = 19) prior to insult. At time 0, the carotid arteries were ligated and the blood pressure was reduced by one third by hemorrhage. At 15 minutes, inspired oxygen was reduced from 50% to 6%. At 30 minutes, inspired oxygen was changed to 100%, carotid ligatures were released, and the withdrawn blood was reinfused. An additional 14 piglets received 3 mg/kg MK-801 but not hypoxic-ischemic injury (drug-only group), and a final group of 11 piglets were subjected to only a sham operation (sham group).


RESULTS
Neurological examination scores at 24, 48, and 72 hours showed that MK-801 and drug-only piglets were significantly worse than the controls. Pathological examination of the brains at 72 hours showed significantly greater damage in the brains of the MK-801 and control pigs relative to the sham and drug-only groups. No differences were found between the control and the MK-801 groups. No differences were found between the sham and drug-only groups.


CONCLUSIONS
MK-801, at a dose of 3 mg/kg, causes neurological dysfunction in piglets lasting at least 72 hours, but neither causes brain damage nor ameliorates the effects of hypoxic-ischemic injury to the brain of the newborn pig.
Department of Pediatrics, University of Mississippi Medical Center, Jackson 39216-4505.
M H
MH
LeBlanc
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V
Vig
B
B
Smith
C C
CC
Parker
O B
OB
Evans
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Smith
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D002339:Carotid Arteries / Q000601:surgery; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008026:Ligation; D010100:Oxygen / Q000378:metabolism; D013552:Swine
D016291:Dizocilpine Maleate; D010100:Oxygen