Role of mitochondrial permeability transition in fetal brain damage in rats

Nakai, Akihito; Shibazaki, Yukino; Taniuchi, Yoshinari; Miyake, Hidehiko; Oya, Atsuko; Takeshita, Toshiyuki

doi:10.1016/j.pediatrneurol.2003.09.006

« Previous Next »Pediatric Neurology
Volume 30, Issue 4 , Pages 247-253, April 2004

Role of mitochondrial permeability transition in fetal brain damage in rats

Akihito Nakai, MD
- Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan
- Communications should be addressed to:Dr. Nakai; Department of Obstetrics and Gynecology; Tama Nagayama Hospital; Nippon Medical School; 1-7-1 Nagayama; Tama-City; Tokyo, 206-8512; Japan.
Yukino Shibazaki, MD
- Department of Anesthesiology, Jikeikai University School of Medicine, Tokyo, Japan
Yoshinari Taniuchi, MD
- Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan
Hidehiko Miyake, MD
- Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan
Atsuko Oya, MD
- Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan
Toshiyuki Takeshita, MD
- Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan

Received 3 June 2003; accepted 9 September 2003.

Abstract

Recirculation after transient in utero ischemia has previously been found to be accompanied by delayed deterioration of cellular bioenergetic state and of mitochondrial function in the fetal rat brain. Our objective was to assess whether the delayed deterioration is a result of the activation of mitochondrial permeability transition which is observed ultrastructurally as mitochondrial swelling. The respiratory activities and ultrastructure of isolated mitochondria and the cellular bioenergetic state in fetal rat brain were examined at the end of 30 minutes of in utero ischemia and after 1, 2, 3 and 4 hours of recirculation. Cyclosporin A, a potent and virtually specific mitochondrial permeability transition blocker, or vehicle was administered 1 hour after recirculation. In the vehicle-treated animals, the transient ischemia was associated with a delayed deterioration of cellular bioenergetic state and mitochondrial activities at 4 hours of recirculation. The number of swollen mitochondria increased markedly after 4 hours of recirculation. The deterioration and the swelling were prevented by cyclosporin A. The present study indicates that cyclosporin A treatment improves recovery of fetal brain energy metabolism and inhibits the mitochondrial swelling after transient in utero ischemia. The results suggest that mitochondria and mitochondrial permeability transition may be involved in the development of ischemic brain damage in the immature rat.Nakai A, Shibazaki Y, Taniuchi Y, Miyake H, Oya A, Takeshita T. Role of mitochondrial permeability transition in fetal brain damage in rats. Pediatr Neurol 2004;30:247-253.