PS-334 Biomarkers Of Delayed Brain Development In A Pig Model Of Preterm Birth

Background and aims Neurodevelopmental seqeulae of premature birth involve cognitive and motor deficits, often persisting into adult life. The molecular mechanisms involved remain yet to be elucidated, but certain regions e.g. cerebellum and neocortex appear particularly sensitive. The current study aimed to evaluate the relevance of Brain derived neurotropic factor (BDNF), involved in the formation of synaptic connexions, and Sonic Hedgehog (SHH), important for perinatal neuronal differentiation, as potential biomarkers of brain development. Methods Piglets were born via planned C-section either at full term (gestational age 118d) or 12 days preterm. Euthanization and brain dissection was performed at postnatal day 5 (n = 11, n = 33) and day 26 (n = 22, n = 18), for terms and preterms respectively. BDNF and SHH levels were analysed by ELISA in pig cerebellar homogenates. Western blotting (WB) of downstream targets for BDNF (TrkB) and SHH (Patched, Smoothened, Gli-1) were included together with qPCR-array of 84 neurogenesis pathway related genes (including Bdnf and Shh) on cerebellar and prefrontal cortical tissue. Results Overall BDNF analysis showed no differences between term and preterm brains but levels were significantly different between day 5 and 26 in preterms only. SHH appeared to be lower in preterms compared to terms, but only significantly on Day 26. Conclusions The reduced levels of SHH, specifically at day 26, suggest that SSH may be a useful biomarker for delayed brain development and indicate that the pig may provide a relevant model to study the premature brain.