Quantitative assessment of new cell proliferation in the dentate gyrus and learning after isoflurane or propofol anesthesia in young and aged rats

Abstract

There is a growing body of evidence showing that a statistically significant number of people experience long-term changes in cognition after anesthesia. We hypothesize that this cognitive impairment may result from an anesthetic-induced alteration of postnatal hippocampal cell proliferation. To test this hypothesis, we investigated the effects of isoflurane and propofol on new cell proliferation and cognition of young (4 month-old) and aged (21 month-old). All rats were injected intraperitoneally (IP) with 50 mg/kg of 5-bromo-2-deoxyuridine (BrdU) immediately after anesthesia. A novel appetitive olfactory learning test was used to assess learning and memory two days after anesthesia. One week after anesthesia, rats were euthanized and the brains analyzed for new cell proliferation in the dentate gyrus, and proliferation and migration of newly formed cells in the subventricular zone to the olfactory bulb. We found that exposure to either isoflurane (p=0.017) or propofol (p=0.006) decreased hippocampal cell proliferation in young, but not in aged rats. This anesthetic-induced decrease was specific to new cell proliferation in the hippocampus, as new cell proliferation and migration to the olfactory bulb was unaffected. Isoflurane anesthesia produced learning impairment in aged rats (p=0.044), but not in young rats. Conversely, propofol anesthesia resulted in learning impairment in young (p=0.01), but not in aged rats. These results indicate that isoflurane and propofol anesthesia affect postnatal hippocampal cell proliferation and learning in an age dependent manner.