Peasley, Melissa A., and Riyi Shi. Resistance of isolated mammalian spinal cord white matter to oxygen-glucose deprivation. Am J Physiol Cell Physiol 283: C980-C989, 2002. First published May 22, 2002 10.1152/ajpcell.00591.2001We found that isolated guinea pig spinal cord white matter is resistant to acute oxygen-glucose deprivation. Sixty minutes of oxygen-glucose deprivation resulted in a 60% reduction of compound action potential (CAP) conductance, and there was a near complete recovery after 60 min reperfusion. Corresponding horseradish peroxidase-exclusion assay showed little axonal membrane damage. To further deprive the axons of metabolic substrate, we added 2 mM sodium cyanide or 2 mM sodium azide, both mitochondrial suppressors, to the ischemic medium, which completely abolished CAP and resulted in a 15 to ϳ30% recovery postreperfusion. Both compounds preferentially reduced the conductance of large diameter axons. We suggest the residual ATP in our ischemic model can protect anatomic integrity and physiological functioning of spinal axons following ischemic insult. This further suggests that oxygen-glucose deprivation alone cannot be solely responsible for short-term functional and anatomic damage. The damaging effects of ischemia in vivo may be mediated by factors originating from the gray matter of the cord or other systemic factors; both were largely eliminated in our in vitro white matter preparation.axons; neurotrauma; reperfusion; mitochondria; membrane OXYGEN-GLUCOSE DEPRIVATION, or ischemia, can produce or exacerbate many devastating insults to the central nervous system (CNS), such as stroke and paralysis (1,21,29,31,35,36). In the case of spinal cord injury, paralysis can be a consequence of even brief ischemic episodes such as result from clamping of the aorta during life-saving surgeries (1,7,12,13,19). Furthermore, ischemia can arise secondary to physical insults when the integrity of blood vessels is compromised (20,35,36). Altogether, it is widely recognized that ischemia plays a critical role in the neuropathology of the CNS in general and the spinal cord in particular (20,29,31).Although there is little doubt that ischemia causes cellular damage, the mechanism of just how ischemia can produce such damage at the cell and tissues level of organization is not fully understood. This is because ischemia has been shown to activate many physiological and/or chemical pathways, such as prolonging neurotransmitter release, elevation of reactive oxygen species, and the increase of calcium influx due to membrane depolarization (6,16,18,35). It is possible that these secondary effectors, not oxygen-glucose deprivation alone, are the real culprits in causing cellular damage. It is also possible that there is a hierarchy of importance when each of these mechanisms acts in concert to cause cell damage, though some mechanisms may be more damaging to the cell than others. In our opinion, it is difficult to investigate these possibilities in the absence of a model where the overall condition of the cord,...