An experimental model combining microdialysis with electrophysiology, histology, and neurochemistry for exploring mechanisms of secondary damage in spinal cord injury: effects of potassium.
An experimental model for characterizing effects of agents suspected to cause damage secondary to spinal cord injury is presented. Microdialysis was used to administer candidate damaging agents and to sample the release of other substances in response to administered agents. Damage was assessed by monitoring the amplitudes of evoked potentials during candidate administration and by postmortem histologic examination. This approach enabled the correlation of electrophysiologic, histologic, and neurochemical parameters in the same experiment. Potassium was chosen as a candidate damaging agent, because (1) in high extracellular concentrations it destroys neurons and (2) its extracellular concentration rises substantially following impact injury to the spinal cord. A technique using parallel administering and collecting microdialysis fibers was developed to estimate the in vivo concentration of K+ outside the administering fiber. Administration of 100 mM KCl, 50 mM K2HPO4, or 100 mM potassium glucuronate in artificial cerebrospinal fluid blocked electrical conduction and destroyed cell bodies. Release of the neurotransmitter amino acids aspartate, glutamate, glycine, and gamma-aminobutyric acid (GABA) and the possible neurotransmitter taurine were dramatically increased by administration of 100 mM KCl. Levels of non-neurotransmitter amino acids increased to lesser degrees. Impairment of conduction, destruction of cell bodies, and release of excitotoxins were all consistent with elevated K+ serving as a secondary damaging agent in spinal cord injury.
Liu
D
D
Marine Biomedical Institute, University of Texas Medical Branch, Galveston.
McAdoo
D J
DJ
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004553:Electric Conductivity; D004558:Electric Stimulation; D004594:Electrophysiology; D008297:Male; D017551:Microdialysis; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000503:physiopathology; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*
D000596:Amino Acids; D011188:Potassium