Fetal surgery decreases anesthesia-induced neuroapoptosis in the mid-gestational fetal ovine brain

Background: Studies demonstrating an association between anesthesia and brain cell death (neuroapoptosis) in young animals were performed without accompanying surgery. This study tests the hypothesis that fetal surgery decreases anesthesia-induced neuroapoptosis. Materials and Methods: Seventy-day-pregnant ewes received 2% isoflurane for 1 h (low dose [LD]) or 4% for 3 h (high dose [HD]) with or without fetal surgery (S). Unexposed fetuses served as controls (C). Fetal brains were processed for neuroapoptosis using anti-caspase-3 antibodies. Data were analyzed using ANOVA. Results: Twenty-eight fetal sheep were evaluated. Dentate gyrus neuroapoptosis was lower in the HD+S group (13.1 ± 3.76 × 10⁵/mm³) than in the HD (19.1 ± 1.40 × 10⁵/mm³, p = 0.012) and C groups (18.3 ± 3.55 × 10⁵/mm³, p = 0.035). In the pyramidal layer of the hippocampus, neuroapoptosis was lower in the HD+S group (8.11 ± 4.88 × 10⁵/mm³) than in the HD (14.8 ± 2.82 × 10⁵/mm³, p = 0.006) and C groups (14.1 ± 4.54 × 10⁵/mm³, p = 0.019). The LD+S group showed a trend towards a significant decrease in neuroapoptosis in the pyramidal layer (LD+S 7.51 ± 1.48 vs. LD 13.5 ± 1.87 vs. C 14.1 ± 4.54 × 10⁵/mm³, p = 0.07) but not in the dentate gyrus. Fetal surgery did not affect neuroapoptosis in the frontal cortex or endplate. Conclusions: Fetal surgery decreases isoflurane-induced neuroapoptosis in the dentate gyrus and the pyramidal layer of mid-gestational fetal sheep. Long-term effects of these observations on memory and learning deserve further exploration.