///2010 Abstract Details
2010 Abstract Details2018-05-01T17:52:49+00:00

RAT OFFSPRING EXPOSED TO ISOFLURANE DURING EARLY GESTATION ARE BEHAVIORALLY ABNORMAL AS ADULTS

Abstract Number: 66
Abstract Type: Original Research

Arvind Palanisamy M.B.B.S, M.D, F.R.C.A1 ; Mark G Baxter Ph.D2; Zhongcong Xie M.D, Ph.D3; Rudolph E Tanzi Ph.D4; Gregory Crosby M.D5; Deborah J Culley M.D6

Introduction: Several lines of preclinical evidence suggest that commonly used anesthetic agents, particularly inhalational agents, induce long-lasting neurobehavioral changes when administered early in life.(1) Toxic effects occur during synapse formation, a phase that begins during the third trimester in humans,(2) but have not been studied at earlier time points corresponding to those at which most non-obstetric surgeries and fetal interventions occur. Our study was designed to simulate second trimester exposure to a prototypical inhalational anesthetic, followed by behavioral characterization of the offspring during adulthood.

Methods: After institutional animal board approval, 3 pregnant rats received 1.4% isoflurane in 100% oxygen for 4 hours on gestational day 14 (E14), the equivalent of second trimester in humans;(3) 2 pregnant rats that received 100% oxygen in an identical chamber for the same duration served as controls. Male offspring were behaviorally characterized beginning at 8 weeks of age, which is early adulthood for a rodent. Behaviors examined included motor activity (spontaneous locomotor activity), spatial working memory (spontaneous alternation task, radial arm maze), anxiety (elevated plus maze), and object recognition memory (novel object recognition task). Radial arm maze data were analyzed with repeated measures ANOVA, with anesthesia group as the between-subjects factor and the day of testing as the within-subjects factor; all other data were analyzed with Students t-test.

Results: Isoflurane anesthesia was physiologically well tolerated by the pregnant rats. Adult male rats exposed prenatally to isoflurane showed an array of learning and behavioral disturbances compared to rats born to oxygen-exposed controls. These included impairment of spatial working memory as evidenced by an increase in the time taken to complete the maze task (P = 0.01) and the number of omission errors (P = 0.006), reduced anxiety as demonstrated by an increase in both the number of entries and time spent in the open arms (P = 0.015 and 0.038 respectively), and a preference for familiar rather than novel objects (P = 0.017). In addition, prenatally exposed rats were hyperlocomotor on several tasks but the results did not reach statistical significance.

Conclusions: These data support the notion that isoflurane is detrimental to the developing rodent brain and identify E14, which corresponds to the second trimester in humans, as a period of risk. The behavioral phenotype we observed is reminiscent of ADHD-autistic spectrum disorders and suggests that prenatal exposure to general anesthetics may produce social as well as cognitive deficits into adulthood.

References: 1. V. Jevtovic-Todorovic et al., J Neurosci 23, 876 (Feb 1, 2003).2. J. Dobbing, J. Sands, Early Hum Dev 3, 79 (Mar, 1979).3. B. Clancy et al., Neuroinformatics 5, 79 (Spring, 2007).

SOAP 2010