Development of a robust animal model for periventricular leukomalacia

Abstract

The objective of the study was to develop a robust animal model for periventricular leukomalacia The animal model was developed using a combination of three insults Prenatal inflammation by intraperitoneal injection of lipopolysaccharide to the dam on embryonic day 18 Prenatal near total ischemia by clamping of bilateral uterine and ovarian arteries for 30 minutes on E19 and Postnatal recurrent hypoxia with 6 percent oxygen for 40 minutes on days 2 to 4 The pups were assessed for neuromotor and neurocognitive functions Pathological analysis of pup brains was performed on day 28 Immunohistochemical analysis was performed using antibodies to MBP to assess myelination NeuN to assess neuronal density and organization and GFAP to assess gliosis We had 33 pups in experimental LIH group and 34 normal pups as controls Histopathological analysis of rat pup brains showed white matter injury in 58 percent pups with findings such as ventricular dilatation suggestive of periventricular white matter loss and thinning and rarefaction of corpus callosum Immunohistochemistry with MBP showed myelin loss in corpus callosum or periventricular white matter in 100 percent pups in LIH group Nissl stain showed focal to generalized cortical disorganization in LIH pups without neuronal loss On functional assessment LIH pups had prolonged escape latency in morris water maze test suggestive of cognitive and memory impairment and less rearings in actiphototmeter suggestive of reduced exploratory behavior We have successfully developed a robust animal model for PVL The animal model resembles non cystic PVL in both pathological and functional analysis newline newline newline