412 Neurobehavioural and neuropathological consequences of fetal growth restriction in a rabbit model

Abstract

To characterize the behavioural and neuropathological effects in a uteroplacental ligation FGR rabbit model. At gestational day (GD) 25, time mated does underwent partial uteroplacental vessel ligation (UPVL) in one randomly chosen horn, leaving the contralateral foetuses as internal controls. Does were delivered at GD 30 by C-section, and neurobehavioural assessment (NBA) was performed 24h after delivery. Thereafter neonates were transcardially perfused with heparinised saline and 4% paraformaldehyde. Brains were further immerse-fixated for 72 hrs, weighed, embedded and serial sectioned. Slides were stained with Cresyl violet, scanned, and neuron count was performed manually using QuPath software by an evaluator blinded to the specimen allocation. Brain slides from 12 cases and 12 controls were selected according to sample quality. Normal distribution was assessed by Shapiro-Wilk test and data presented as a mean with standard deviations or median and interquartile ranges. The comparison was done by unpaired students t-test or Mann Whitney test. A p-value < 0.05 was considered significant. Neonatal survival was 45% (27/60) in the ligated and 85% (44/52) in the non-ligated horn. UPVL resulted in lower birth weight (35.00±7.14 g vs. 39.05±9.94 g; p<0.05), and no difference in brain-to-body weight ratio (0.046±.005 vs. 0.044±.006; p=0.7). FGR resulted in significantly lower motor (19±4.25 vs. 20±2, p=0.007) and sensory scores (12±4 vs. 14±1.25, p=0.003) on early NBA, and was associated with lower neuron density in the prefrontal cortex (227.8±67 vs. 327±115 n/mm2; p<0.05), caudate nucleus (533.3±85 vs. 444.2±50 n/mm2; p<0.01), and dentate gyrus (222.5±34 vs. 292±49 n/mm2; p=0.001). FGR is associated with functional neurological impairment and structural alterations in the prefrontal cortex, basal ganglia and hippocampus in this rabbit model