Background and Purpose-Intraventricular hemorrhage (IVH) is a common complication of prematurity that results in neurological sequelae, including cerebral palsy, posthemorrhagic hydrocephalus, and cognitive deficits. Despite this, there is no standardized animal model exhibiting neurological consequences of IVH in prematurely delivered animals. We asked whether induction of moderate-to-severe IVH in premature rabbit pups would produce long-term sequelae of cerebral palsy, posthemorrhagic hydrocephalus, reduced myelination, and gliosis. Methods-The premature rabbit pups, delivered by cesarean section, were treated with intraperitoneal glycerol at 2 hours postnatal age to induce IVH. The development of IVH was diagnosed by head ultrasound at 24 hours of age. Neurobehavioral, histological, and ultrastructural evaluation and diffusion tensor imaging studies were performed at 2 weeks of age. Results-Although 25% of pups with IVH (IVH pups) developed motor impairment with hypertonia and 42% developed posthemorrhagic ventriculomegaly, pups without IVH (non-IVH) were unremarkable. Immunolabeling revealed reduced myelination in the white matter of IVH pups compared with saline-and glycerol-treated non-IVH controls. Reduced myelination was confirmed by Western blot analysis. There was evidence of gliosis in IVH pups. Ultrastructural studies in IVH pups showed that myelinated and unmyelinated fibers were relatively preserved except for focal axonal injury. Diffusion tensor imaging showed reduction in fractional anisotropy and white matter volume confirming white matter injury in IVH pups. Conclusion-The

Objective Absence epilepsy is a common seizure disorder in children which can produce chronic psychosocial sequelae. Human patients and rat absence models show bilateral spike-wave discharges (SWD) in cortical regions. We employed diffusion tensor imaging (DTI) in rat absence models to detect abnormalities in white matter pathways connecting regions of seizure activity. Methods We studied Wistar albino Glaxo rats of Rijswijk (WAG/Rij), genetic absence epilepsy rats of Strasbourg (GAERS), and corresponding nonepileptic control strains. Ex vivo DTI was performed at 9.4T with diffusion gradients applied in 16 orientations. We compared fractional anisotropy (FA), perpendicular (λ⊥) and parallel (λ∥) diffusivity between groups using t-maps and region of interest (ROI) measurements. Results Adult epileptic WAG/Rij rats exhibited a localized decrease in FA in the anterior corpus callosum. This area was confirmed by tractography to interconnect somatosensory cortex regions most intensely involved in seizures. This FA decrease was not present in young WAG/Rij rats before onset of SWD. GAERS, which have more severe SWD than WAG/Rij, exhibited even more pronounced callosal FA decreases. Reduced FA in the epileptic animals originated from an increased λ⊥ with no significant changes in λ∥. Interpretation Reduced FA with increased λ⊥ suggests that chronic seizures cause reduction in myelin or decreased axon fiber density in white matter pathways connecting regions of seizure activity. These DTI abnormalities may improve the understanding of chronic neurological difficulties in children suffering with absence epilepsy, and may also serve as a noninvasive biomarker for monitoring beneficial effects of treatment.