Potential of the ovine brain as a model for anesthesia-induced neuroapoptosis.

Olutoye, Olutoyin A; Lazar, David A; Akinkuotu, Adesola C; Adesina, Adekunle; Olutoye, Oluyinka O

PURPOSE This study aimed to determine the feasibility of the fetal ovine model for anesthesia-induced neuroapoptosis detection and effect of dexmedetomidine on neuroapoptosis. METHODS Brains of fetal lambs that underwent tracheal occlusion for congenital diaphragmatic hernia were studied following anesthetic exposure. The brains of nine fetuses from six pregnant sheep were studied. Seven of these fetuses underwent surgery for tracheal balloon insertion at 118-120 days gestational age (GA) under 1.5-2.0% isoflurane for 2-3 h. Two weeks afterward, at balloon retrieval, a repeat anesthetic: 1.5-2% isoflurane for 6 h was administered. Five of these fetuses were also exposed to dexmedetomidine concurrently. Immunohistochemistry of fetal brains for apoptotic neurons using activated caspase-3 antibodies was compared to that of an unexposed control group at GA 109 and 122 days. RESULTS Neuroapoptosis was detected in the ovine fetus with GA- dependent variation observed in the hippocampus. Increased neuroapoptosis occurred in the isoflurane-only group. Fetuses with isoflurane-dexmedetomidine exposure exhibited decreased neuroapoptosis compared to isoflurane-only group. CONCLUSION The fetal ovine model is a suitable option for neuroapoptosis analysis. Isoflurane use appears to be associated with additional neuroapoptosis in ovine fetuses undergoing surgical stimulation. Possible amelioration of isoflurane-induced neuroapoptosis by dexmedetomidine deserves further study. Further studies of the effect of gestational age, dose, duration of anesthesia and surgical stimulation on neuroapoptosis are needed.