Abstract
BackgroundOur previous research showed that 4 h of maternal anesthesia with isoflurane during early gestation in pregnant rats leads to a deficit in spatial memory of adult male offspring. Because spatial memory is predominantly a hippocampally-mediated task, we asked the question if early gestational exposure to isoflurane affects development of the hippocampus in the offspring.FindingsPreviously behaviorally characterized adult male rats that were exposed to isoflurane during second trimester were sacrificed at 4 months of age (N = 10 and 13, control and isoflurane groups, respectively) for quantitative histology of hippocampal subregions. Sections were stained with cresyl violet and the total number of cells in the granular layer of the dentate gyrus and the pyramidal cell layer in the CA1 region were determined by a blinded observer using unbiased stereological principles and the optical fractionator method. Data were analyzed using Student’s t test; P < 0.05 was accorded statistical significance. Stereological examination revealed 9% fewer cells in the granular layer of the dentate gyrus of isoflurane-exposed adult rats compared to controls (1,002,122 ± 84,870 vs. 1,091,829 ± 65,791, respectively; Mean ± S.D, *P = 0.01). In contrast, there were no changes in the cell number in the CA1 region, nor were there changes in the volumes of both regions.ConclusionsOur results show that maternal isoflurane anesthesia in rodents causes region-specific cell loss in the hippocampus of adult male offspring. These changes may, in part, account for the behavioral deficits reported in adult rats exposed to isoflurane in utero.
Highlights
Despite robust evidence for anesthesia-induced neurotoxicity in postnatal rodent models [1,2,3,4] not much is known about the effects of maternal anesthesia on the fetal brain
Our results show that maternal isoflurane anesthesia in rodents causes region-specific cell loss in the hippocampus of adult male offspring
This is significant because most non-obstetric surgeries and fetal intervention procedures that are performed during the second trimester require maternal anesthesia [5]
Summary
Introduction Despite robust evidence for anesthesia-induced neurotoxicity in postnatal rodent models [1,2,3,4] not much is known about the effects of maternal anesthesia on the fetal brain. We previously showed that a single 4 h exposure to isoflurane during mid-gestation impairs acquisition of spatial memory in the adult male offspring [12]. This suggested that prolonged and unphysiological stimulation of these neurotransmitter mechanisms can be detrimental to fetal brain development. Because spatial memory is predominantly a hippocampally-mediated task, we asked the question if early gestational exposure to isoflurane affects development of the hippocampus in the offspring
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