Effects of Daily versus Weekly Testing and Pre-Training on the Assessment of Neurologic Impairment following Diffuse Traumatic Brain Injury in Rats

Abstract

A number of test paradigms have been used to determine acute and chronic motor and cognitive deficits after experimental traumatic brain injury (TBI). Some involve daily testing of either trained or untrained animals whereas others utilize periodic testing over extended time periods. Which test paradigm is the most appropriate for the assessment of motor and cognitive deficits is, however, unclear. In the current study, we have used both daily and weekly testing in trained and untrained animals to ascertain which assessment protocol is most suited for the detection of functional deficits after diffuse TBI in rats. Animals were subjected to severe injury using the impact-acceleration model of diffuse TBI. An equal number of animals were also prepared surgically but not subject to injury (shams). The rotarod device and the Barnes Maze were used for motor and cognitive assessment respectively, with half of the animals being pre-trained on each test for 10 days prior to injury. The open field test was used to assess spontaneous exploratory activity (stress). Following injury, animals were assessed for neurologic deficits either on a daily basis (for 10 days) or a weekly basis (for 4 weeks). In trained animals, the greatest differences in neurologic outcome between injured and sham animals were observed early after injury. In contrast, in untrained animals, greatest differences between injured and sham animals were observed at later time points. Pre-injury training did not improve the rate of cognitive recover, or the rate of motor recovery in the weekly test paradigm, but did improve the rate of motor recovery in the daily assessment paradigm. Daily assessment promoted rapid functional recovery whereas weekly assessments did not significantly affect outcome in injured animals over the 4-week assessment period. Spontaneous exploratory activity was decreased after TBI and was not influenced by task exposure. These studies demonstrate that the functional assessment paradigm needs to be considered when quantifying functional deficits following diffuse TBI in rats.