Posthemorrhagic ventricular dilation in the neonate: Development and characterization of a rat model

Abstract

Intraventricular hemorrhage is a common complication of prematurity. Posthemorrhagic ventricular dilation (PHVD) has a high rate of disability and no safe and effective treatment. Its pathogenesis is poorly understood, largely because of the lack of a satisfactory animal model. We have developed a model of neonatal PHVD in the rat. Seven-day-old (P7) Wistar rat pups were given 80-μl injections of citrated rat blood or artificial cerebrospinal fluid (CSF) into alternate lateral ventricles on P7 and P8. Intracranial pressure was monitored and increased briefly by over 8-fold. Some rats received further 10-μl intraventricular injections of India ink on P21. Animals were weighed daily and simple neurologic tests performed. On P21 (or P22 if India ink had been injected), the rats were perfusion-fixed and blocks processed for paraffin histology. Sixty-five percent of pups injected with blood and 50% injected with artificial CSF developed dilated lateral ventricles, with patchy loss of ependyma, marked astrocytic gliosis, and rarefaction of periventricular white matter, India ink injection revealed slow transit of CSF from the dilated lateral ventricles but eventual passage into the subarachnoid space. Pups that had received intraventricular injections but did not develop ventricular dilation nonetheless had lighter brains than littermate controls (p < 0.001). Body weights were not significantly different from controls. Hydrocephalic animals had reduced motor performance as assessed by a grip traction test (p = 0.0002). This model is well suited to studying the pathogenesis of PHVD.