MCI-186 administered to the maternal circulation inhibits fetal brain injury resulting from total umbilical cord occlusion in the chronically instrumented fetal lamb.
OBJECTIVE
To evaluate the transplacental effects of MCI-186 (edaravone), a potent hydroxyl radical scavenger, administered to the maternal circulation to inhibit fetal brain injury caused by umbilical cord occlusion.


METHODS
Nine chronically instrumented lambs were prepared. In three cases, 10-min persistent total umbilical cord occlusion (group A) was performed. Another three cases underwent occlusion and were administered 60 mg of MCI-186 through the maternal femoral vein prior to the end of occlusion (group B). The remaining three cases underwent sham operation (group C). On day 3 after insult, fetal brains were extirpated. Paraffin-embedded brain tissue sections were stained with hematoxylin and eosin, Bodian, Kluver-Barrera, and TUNEL. Neuronal cellular damage was evaluated by two pathologists blinded to the experimental conditions.


RESULTS
Group A displayed numerous cells with eosinophilic condensation of nuclear chromatin and proliferation of microglia in the hippocampus and basal ganglia. TUNEL-positive cells were observed in the periventricular area. Group B showed microglial proliferations, but no marked changes. No pathological changes were apparent in group C.


CONCLUSIONS
MCI-186 administered to the maternal circulation could inhibit fetal brain injury resulting from hypoxia-reperfusion induced by umbilical cord occlusion.
Masaoka
Naoki
N
Department of Obstetrics and Gynecology, Nihon University School of Medicine, Tokyo, Japan. masaoka@med.nihon-u.ac.jp
Nakajima
Yoshiyuki
Y
Watanabe
Masao
M
Hayakawa
Yasuhito
Y
Nagaishi
Masaji
M
Yamamoto
Tatsuo
T
Honma
Taku
T
Oinuma
Toshimichi
T
Nemoto
Norimichi
N
D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001930:Brain Injuries / Q000151:congenital* / Q000473:pathology; D000077553:Edaravone; D005260:Female; D005311:Fetal Hypoxia / Q000097:blood / Q000378:metabolism; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D012039:Regional Blood Flow; D012756:Sheep; D014470:Umbilical Cord / Q000098:blood supply*
D016166:Free Radical Scavengers; D000077553:Edaravone; D000983:Antipyrine