Fetal exposure to high isoflurane concentration induces postnatal memory and learning deficits in rats.
We developed a maternal fetal rat model to study the effects of isoflurane-induced neurotoxicity on the fetuses of pregnant rats exposed in utero. Pregnant rats at gestational day 14 were exposed to 1.3 or 3% isoflurane for 1h. At postnatal day 28, spatial learning and memory of the offspring were examined using the Morris Water Maze. The apoptosis was evaluated by caspase-3 immunohistochemistry in the hippocampal CA1 region. Simultaneously, the ultrastructure changes of synapse in the hippocampal CA1 and dentate gyrus region were observed by transmission electron microscopy (TEM). The 3% isoflurane treatment group showed significantly longer escape latency, less time spent in the third quadrant and fewer original platform crossings in the Morris Water Maze test, significantly increased number and optical densities of caspase-3 neurons. This treatment also produced remarkable changes in synaptic ultrastructure compared with the control and the 1.3% isoflurane groups. There were no differences in the Morris Water Maze test, densities of caspase-3 positive cells, or synaptic ultrastructure between the control and 1.3% isoflurane groups. High isoflurane concentration (3%) exposure during pregnancy caused spatial memory and learning impairments and more neurodegeneration in the offspring rats compared with control or lower isoflurane concentrations.
Department of Anesthesiology, First People's Hospital of Hangzhou, PR China.
Fei-Juan
FJ
Kong
Lei-Lei
LL
Ma
Wen-Wen
WW
Hu
Wen-Na
WN
Wang
Hui-Shun
HS
Lu
Shu-Ping
SP
Chen
D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000201:enzymology / Q000648:ultrastructure; D053148:Caspase 3 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D007530:Isoflurane / Q000633:toxicity*; D007858:Learning / Q000187:drug effects*; D008431:Maternal-Fetal Exchange; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D009474:Neurons / Q000201:enzymology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology / Q000523:psychology*; D051381:Rats
D018685:Anesthetics, Inhalation; D007530:Isoflurane; D053148:Caspase 3