Foetal Growth Restriction Effects on Grey and White Matter in the Prefrontal Cortex and Basal Ganglia of Postnatal Day 10 Piglets

Foetal growth restriction (FGR) is commonly caused by placental insufficiency and increases the risk of perinatal morbidity and mortality. The developing brain is vulnerable to FGR, which can result in adverse long-term neurodevelopmental outcomes. Newborn pigs with spontaneous FGR (<10th centile body weight) and normally grown (NG) littermates were reared to postnatal day 10 (P10; n = 8 FGR and n = 9 NG). Neuropathology was assessed in the prefrontal cortex (PFC) and basal ganglia (BG), which play a key role in cognitive and motor functions. FGR piglets show decreased neuronal count (NeuN) and structural integrity (MAP2) associated with increased apoptotic activity (Casp-3 and -9) in the PFC and BG. Hypomyelination was consistently observed in the white matter of the FGR brain. There was increased microglial activation (Iba-1) and GFAP-positive astrocytes in both the grey and white matter of the PFC and BG, along with increased apoptotic activity in the FGR brain. These findings suggest that the FGR piglet brain shows impaired grey and white matter associated with increased apoptosis in the PFC and BG that persists at P10. Increased glial activation and apoptotic astrocytes may impact neuronal survival and potentially contribute to adverse long-term neurodevelopmental outcomes, highlighting the need for targeted therapeutic interventions to promote effective brain repair in infants with FGR.