Recovery of function after vagus nerve stimulation initiated 24 hours after fluid percussion brain injury

Recent evidence from our laboratory demonstrated in laboratory rats that stimulation of the vagus nerve (VNS) initiated 2 h after lateral fluid percussion brain injury (FPI) accelerates the rate of recovery on a variety of behavioral and cognitive tests. VNS animals exhibited a level of performance comparable to that of sham-operated uninjured animals by the end of a 2-week testing period. The effectiveness of VNS was further evaluated in the present study in which initiation of stimulation was delayed until 24 h post-injury. Rats were subjected to a moderate FPI and tested on the beam walk, skilled forelimb reaching, locomotor placing, forelimb flexion and Morris water maze tasks for 2 weeks following injury. VNS (30 sec trains of 0.5 mA, 20.0-Hz biphasic pulses) was initiated 24 h post-injury and continued at 30-min intervals for the duration of the study, except for brief periods when the animals were detached for behavioral assessments. Consistent with our previous findings when stimulation was initiated 2 h post-injury, VNS animals showed significantly faster rates of recovery compared to controls. By the last day of testing (day 14 post-injury), the FPI-VNS animals were performing significantly better than the FPI-no-VNS animals and were not significantly different from shams in all motor and sensorimotor tasks. Performance in the Morris water maze indicated that the VNS animals acquired the task more rapidly on days 11-13 post-injury. On day 14, the FPI-VNS animals did not differ in the latency to find the platform from sham controls, whereas the injured controls did; however, the FPI-VNS animals and injured controls were not significantly different. Despite the lack of significant histological differences between the FPI groups, VNS, when initiated 24 h following injury, clearly attenuated the ensuing behavioral deficits and enhanced acquisition of the cognitive task. The results are discussed with respect to the norepinephrine hypothesis.