Persistent motor deficit following infusion of autologous blood into the periventricular region of neonatal rats

Abstract

Periventricular hemorrhage (PVH) in the brain of premature infants is often associated with developmental delay and persistent motor deficits. Our goal is to develop a rodent model that mimics the behavioral phenotype. We hypothesized that autologous blood infusion into the periventricular germinal matrix region of neonatal rats would lead to immediate and long-term behavioral changes. Tail blood or saline was infused into the periventricular region of 1-day-old rats. Magnetic resonance (MR) imaging was used to demonstrate the hematoma. Rats with blood infusion, as well as saline and intact controls, underwent behavior tests until 10 weeks age. Blood-infused rats displayed significant delay in motor development (ambulation, righting response, and negative geotaxis) to 22 days of age. As young adults, they exhibited impaired ability to stay on a rotating rod and to reach for food pellets. MR imaging at 10 weeks demonstrated subsets of rats with normal appearing brains, focal cortical infarcts, or mild hydrocephalus. There was a good correlation between MR imaging and histological findings. Some rats exhibited periventricular heterotopia and/or subtle striatal abnormalities not apparent on MR images. We conclude that autologous blood infusion into the brain of neonatal rats successfully models some aspects of periventricular hemorrhage that occurs after premature birth in humans.