title: Dose and duration of nerve growth factor (NGF) administration determine the extent of behavioral recovery following peripheral nerve injury in the rat.
abstract: Nerve growth factor (NGF) has been previously shown to support neuron survival and direct neurite outgrowth in vitro, and to enhance axonal regeneration in vivo. However, a systematic analysis of NGF dose and dose duration on behavioral recovery following peripheral nerve injury in rodents has not been previously investigated. Here, we show that NGF promotes a bell shaped dose-response, with an optimal threshold effect occurring at 800 pg/μl. High dose NGF inhibited regeneration. However, this effect could be reversed through functional blockade of p75 receptors, thus implicating these receptors as mediators of the inhibitory response. Longer term evaluation showed that animals administered NGF at 80 ng/day for 3 weeks had greater sensorimotor recovery compared to all other treatment groups. These animals made significantly fewer errors during skilled locomotion, and displayed both increased vertical and fore-aft ground reaction forces during flat surface locomotion. Furthermore, terminal electrophysiological and myological assessments (EMG, wet gastrocnemius muscle weights) corroborated the behavioral data. Overall, these data support the hypothesis that both appropriate dose and duration of NGF are important determinants of behavioral recovery following nerve injury in the rat.
authors: Department of Clinical Neuroscience, Faculty of Medicine, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1. stephen.kemp@sickkids.ca
authors: Stephen W P
authors: SW
authors: Kemp
authors: Aubrey A
authors: AA
authors: Webb
authors: Sundeep
authors: S
authors: Dhaliwal
authors: Shahbaz
authors: S
authors: Syed
authors: Sarah K
authors: SK
authors: Walsh
authors: Rajiv
authors: R
authors: Midha
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009213:Myography; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D020932:Nerve Growth Factor