Short- and Long-Term Effects of Sodium Phenylbutyrate on White Matter and Sensorimotor and Cognitive Behavior in a Mild Murine Model of Encephalopathy of Prematurity.

Perinatal asphyxia (PA) remains a common cause of neonatal death and long-term disability, with an incidence of 20 per 1000 live births. Even mild PA, without significant neurological distress at birth, is linked to neurodevelopmental disorders. Premature babies are at high risk for both PA and long-term neurobehavioral deficits. The use of peripherally inserted central venous catheters in neonatal intensive care units has reduced mortality and morbidity in preterms. Given their prevalent use and associated complications, such as thrombosis, the present study aimed to investigate the effects of hypoxia associated with the ligation of the external jugular vein (JH model) in 5-day-old mice, whose central nervous system development shares similarities with that of human preterms. Diffuse white matter (WM) injury is associated with later neurodisabilities following very premature birth before 32 weeks of gestation. The present study aimed to investigate whether the murine JH model replicates a key phenotype of non-cystic WM injury, namely permanent hypomyelination and sensorimotor deficits. The second aim was to determine whether sodium phenylbutyrate (PBA), which is already prescribed in neonates for another indication, could prevent these disabilities. JH induced lasting dysmyelination in males, not prevented by PBA, contrary to the discrete JH-induced neurobehavioral deficits observed in both sexes in the short and long term.