HYDROXYL RADICALS GENERATED IN-VIVO KILL NEURONS IN THE RAT SPINAL-CORD - ELECTROPHYSIOLOGICAL, HISTOLOGICAL, AND NEUROCHEMICAL RESULTS

We have used microdialysis to establish an experimental model to chara cterize mechanisms whereby released substances cause secondary damage in spinal cord injury. We use this model here to characterize damaging effects of the hydroxyl radical (OH) in vivo in the spinal cord. OH w as generated in vivo by pumping H2O2 and FeCl2/EDTA through parallel m icrodialysis fibers inserted into the spinal cord. These agents mixed in the tissue to produce OH by Fenton's reaction. Two types of control experiments were also conducted, one administering only 5 mM H2O2 and the other only 0.5 mM FeCl2/0.82 mM EDTA. During administration of th ese chemicals, electrical conduction was recorded as one test for dete rioration. OH blocked conduction completely in 2.5-5 h and Fe2+/EDTA p artly blocked conduction, but H2O2 alone did not cause detectable bloc kage. Histological examination supported the hypothesis that neurons w ere killed by OH, as Fe2+/EDTA and H2O2 alone did not destroy signific ant numbers of neurons. OH, H2O2, and Fe2+ all caused gradual increase s in extracellular amino acid levels. These results are consistent wit h Fe2+-catalyzed free radical generation playing a role in tissue dama ge upon spinal cord injury.