Nerve growth factor and the recovery of behavioral function after focal cortical infarction

The focus of the dissertation was to assess the efficacy of NGF treatment on the recovery of behavioral functions affected by cortical focal ischemia. Forty adult male rats (Sprague-Dawley, 220-260 grams), were randomly assigned to the following four groups: (a) NGF-treated ischemic group (b) Saline-treated ischemic group (c) NGF-treated sham group (d) Saline-treated sham group. Brain ischemia was produced by a permanent occlusion of the left MCA and the ligation of the left CCA, combined with clamping of the right CCA for 60 minutes (MCAo + CCAo). Surgery was performed using a stereo-microscope, a dental drill, microscissors, and bipolar radiofrequency forceps. Immediately after surgery, and during the following three days, rats received an intraventricular injection of either 10ug of NGF dissolved in 5ul of saline or saline alone. Rats were tested in four sensori-motor tasks (tail-hang test, prehensile-traction test, pole latency test, and inclined plane test) and in an activity chamber two weeks post surgery. Spatial reversal learning in a two lever operant chamber started 15 days post surgery and continued for 10 testing days. Results indicate that ischemia produced by the MCAo + CCAo procedure induces behavioral deficits that are task-specific. The ischemic injury resulted in sensory-motor deficits but did not affect spontaneous motor activity or cognitive function. Acute NGF treatment during the early stages of brain ischemia resulted in improved performances on the majority of those behaviors that were affected by the ischemic insult. Results suggest that the MCAo + CCAo model of ischemia is a suitable model to explore NGF effects due to its acute effects on behavior and responsiveness to treatment.