Development of a New Animal Model for Non-Cystic Periventricular Leukomalacia

Periventricular leukomalacia (PVL) is a major cause of cerebral palsy in preterm neonates. Though many interventions are being explored as therapeutic options in PVL, all these therapies are still in preclinical phase. This emphasizes the need for the development of robust animal models for PVL. We aimed to develop a new animal (rat) model for PVL using natural pattern of perinatal insults as in humans. The animal model was developed using a combination of three insults: prenatal inflammation, prenatal near total ischemia and postnatal recurrent hypoxia. Pathological and immunohistochemical analysis of pup brains was performed on day 28. We had 33 pups in experimental (inflammation, ischemia and hypoxia, LIH) group and 34 normal pups as controls. Histopathological analysis and immunohistochemistry with anti myelin basic protein (MBP) antibody showed myelin loss in corpus callosum or periventricular white matter in all pups in LIH group. Nissl's stain showed focal to generalized cortical disorganization. On functional assessment, LIH pups had prolonged escape latency in morris water maze test suggestive of cognitive/memory impairment. To conclude, we have developed a new animal model for PVL in rat, using a similar pattern of perinatal insults as in human preterm neonates. The model resembles non-cystic PVL in both pathological and functional analysis.