Peripheral neuropathies which appreciably interfere with rehabilitation are frequent following severe thermal burns. Little is known of their cause. This project examines the effect of thermal injury on peripheral nerve structure, function and composition. The experiments are designed to answer in part the following questions: What are the functional, morphological and some of the compositional changes that occur in nerves of differing modality following burn injury? Is there preferential involvement and, if so, what are the determinants? Are the changes limited to nerves which have been directly injured? What is the temporal course of evolvement? Is acute nerve dysfunction from direct thermal injury aggravated by compressive extrinsic edema? What is the role of endoneurial edema? Our investigations to dat suggest that there is a differential order of susceptibility of fibers to both in vitro and in vivo injury, which may be primarily related to their functional role rather than to their dimensions or other anatomical characteristics. In this project, the response of the rat sciatic nerve to direct heat injury in vivo and/or in vitro is examined and compared to normal and to the contralateral uninjured nerve. A radio frequency generator is used to deliver all heat loads. The evolution of (motor) neuropathy is documented by percutaneous electrophysiological assessment and by clinical evaluation (distal motor, sensory deficits) in previously injured animals. At intervals following injury, the sciatic and its major branches (the mainly motor peroneal, the mainly sensory sural and the mixed posterior tibial) are harvested and the nerve action potentials examined in vitro in a Harvard chamber under carefully controlled conditions. Response to a second in vitro heat load is assessed. Nerves from similarly injured animals are harvested in parallel experiments and examined by light and electron microscopy. Nerve water content is measured and endoneurial permeability assessed by colorimetric determination of Evans blue content and, qualitatively, by the use of an electron opaque lanthanum tracer. Changes in nerve protein are assessed using polyacrylamide gel electrophoresis and high pressure liquid chromatography. The effects of intravenous fluid therapy and of surgical wound decompression on nerve structure, function and composition is evaluated. The proposed study brings together three investigators, one with expertise in the physiology and clinical management of burns, one with experience in peripheral nerve function and physiology, and one expert in neuropathological and morphological assessment of changes occurring in different experimental neurophatological conditions.
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