Long-term dysfunction following diffuse traumatic brain injury in the immature rat

Abstract

Children often suffer sustained cognitive dysfunction after severe diffuse traumatic brain injury (TBI). To study the effects of diffuse injury in the immature brain, we developed a model of severe diffuse impact (DI) acceleration TBI in immature rats and previously described the early motor and cognitive dysfunction posttrauma. In the present study, we investigated the long-term functional ability after DI (150 gm/2 m) compared to sham in the immature (PND 17) rat. Beam balance and inclined plane latencies were measured daily for 10 days after injury to assess gross vestibulomotor function. The Morris water maze (MWM) paradigm was evaluated monthly up to 3 months after DI and sham injuries. Reduced latencies on the balance beam and inclined plane were observed in DI rats (p < 0.05 vs. sham [n = 10 per group]) at 24 h and persisted for 10 days postinjury. DI produced sustained MWM performance deficits (p < 0.05 vs. sham) as indicated by the greater latencies to find the hidden platform remarkably through 90 days after injury. Lastly, the brain and body weights of the injured animals were less than sham (p < 0.05) after 3 months. We conclude that a diffuse TBI in the immature rat: (a) created a consistent, marked, but reversible motor deficit up to 10 days following injury; (b) produced a long-term, sustained performance deficit in the MWM up to 3 months posttrauma; and (c) affected body and brain weight gain in the developing rat through 3 months after injury. This TBI model should be useful for the testing of novel therapies and their effect on long-term outcome and development in the immature rat.