Experimental Spinal Cord Injury: Spatiotemporal Characterization of Elemental Concentrations and Water Contents in Axons and Neuroglia

1 Department of Anesthesiology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York 10467; 2 Department of Anesthesiology, Nihon University Hikarigaoka Hospital, Tokyo 179-0072, Japan; and 3 Division of Neurosurgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7060 LoPachin, Richard M., Christopher L. Gaughan, Ellen J. Lehning, Yoshiro Kaneko, Thomas M. Kelly, and Andrew Blight. Experimental Spinal Cord Injury: Spatiotemporal Characterization of Elemental Concentrations and Water Contents in Axons and Neuroglia. J. Neurophysiol. 82: 2143-2153, 1999. To examine the role of axonal ion deregulation in acute spinal cord injury (SCI), white matter strips from guinea pig spinal cord were incubated in vitro and were subjected to graded focal compression injury. At several postinjury times, spinal segments were removed from incubation and rapidly frozen. X-ray microanalysis was used to measure percent water and dry weight elemental concentrations (mmol/kg) of Na, P, Cl, K, Ca, and Mg in selected morphological compartments of myelinated axons and neuroglia from spinal cord cryosections. As an index of axon function, compound action potentials (CAP) were measured before compression and at several times thereafter. Axons and mitochondria in epicenter of severely compressed spinal segments exhibited early (5 min) increases in mean Na and decreases in K and Mg concentrations. These elemental changes were correlated to a significant reduction in CAP amplitude. At later postcompression times (15 and 60 min), elemental changes progressed and were accompanied by alterations in compartmental water content and increases in mean Ca. Swollen axons were evident at all postinjury times and were characterized by marked element and water deregulation. Neuroglia and myelin in severely injured epicenter also exhibited significant disruptions. In shoulder areas (adjacent to epicenter) of severely injured spinal strips, axons and mitochondria exhibited modest increases in mean Na in conjunction with decreases in K, Mg, and water content. Following moderate compression injury to spinal strips, epicenter axons exhibited early (10 min postinjury) element and water deregulation that eventually recovered to near control values (60 min postinjury). Na + channel blockade by tetrodotoxin (TTX, 1 µM) perfusion initiated 5 min after severe crush diminished both K loss and the accumulation of Na, Cl, and Ca in epicenter axo