Maternal treatment with NMDA receptor antagonist (MK-801) attenuates delayed mitochondrial dysfunction after transient intrauterine ischemia in the neonatal rat brain.
OBJECTIVE
Mitochondrial respiratory activities were measured in neonatal rat brains to evaluate the influence of transient intrauterine ischemia on the near-term fetus and to assess the effect of dizocilpine maleate (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist.


METHODS
Transient intrauterine ischemia was induced by 30 min of right uterine artery occlusion at 17 days of gestation in Wistar rats. Vehicle (saline) or 0.5 mg/kg of MK-801 was administered after 1 h of recirculation. All of the pups were delivered by cesarean section at 21 days of gestation and samples of cerebral cortical tissue were obtained from pups at 1 h after birth. Adenosine diphosphate (ADP)-stimulated, nonstimulated, and uncoupled respirations were measured polarographically in homogenates. The respiratory control ratio was defined as ADP-stimulated divided by non-stimulated respiration.


RESULTS
In the vehicle-treated group the neonatal cortical tissue exposed to ischemia showed a significant decrease in ADP-stimulated respiration and respiratory control ratio compared with these findings in normoxic control animals. The delayed mitochondrial respiratory dysfunction was prevented by MK-801, given 1 h after the start of recirculation (P < 0.05).


CONCLUSIONS
The present results indicate that transient intrauterine ischemia in the near-term rat fetus is associated with delayed mitochondrial dysfunction in the neonatal brain; the results suggest that maternal treatment with MK-801 attenuates the deterioration, even when administered 1 h after the start of recirculation.
Department of Obstetrics and Gynecology, Nippon Medical School, Tama, Tokyo, Japan.
A
A
Nakai
Y
Y
Shibazaki
Y
Y
Taniuchi
T
T
Koshino
K
K
Yokoyama