Release of neurotransmitters is thought to cause substantial secondary damage upon injury to CNS tissue, a major health care issue. This project will examine the role of released neurotransmitters in secondary damage accompanying injury to the spinal cord. We have previously demonstrated release of several neurotransmitters upon injury to the spinal cord.
Specific aims are to examine the release of additional neurotransmitters, to determine whether damaging compounds released cause further release of deleterious substances, to determine by histological and electrophysiological methods if candidate substances are damaging, to determine the effect of blocking agents on the release of damaging substances, to evaluate the contributions of reversed membrane transport as opposed to synaptic processes on neurotransmitter release during injury, and to determine whether there are changes in extracellular Mg2+ that could influence the severity of secondary injury processes. The cord will be injured by a weight drop method. In some experiments, the effect of blocking agents on neurotransmitter release during injury will be established. Damage of the cord by administering candidate damaging substances will be determined by histology and electrophysiology. Fluid from within the cord will be sampled and drugs administered through a microdialysis fiber implanted into the cord. Chemical assays will be performed, chiefly by high pressure liquid chromatography, on fluid so collected.
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