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 characterize 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. was generated in vivo by pumping H2O2 and FeCl2/EDTA through parallel microdialysis 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 these chemicals, electrical conduction was recorded as one test for deterioration. OH. blocked conduction completely in 2.5-5 h and Fe2+/EDTA partly blocked conduction, but H2O2 alone did not cause detectable blockage. Histological examination supported the hypothesis that neurons were killed by OH., as Fe2+/EDTA and H2O2 alone did not destroy significant numbers of neurons. OH., H2O2, and Fe2+ all caused gradual increases in extracellular amino acid levels. These results are consistent with Fe(2+)-catalyzed free radical generation playing a role in tissue damage upon spinal cord injury.
Liu
D
D
Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77555.
Yang
R
R
Yan
X
X
McAdoo
D J
DJ
D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D013997:Time Factors
D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007501:Iron