Differential sensitivity to hypoxia of the peripheral versus central trajectory of primary afferent axons

Abstract Myelinated primary afferent fibers have both peripheral and central nervous system components. As the fibers course through peripheral nerve and dorsal roots they are myelinated by Schwann cells, but after they invade the spinal cord they become myelinated by oligodendrocytes and have associations with astrocytes. This presents the opportunity to compare the pathophysiology of PNS (Schwann cell-associated) vs. CNS (oligodendrocyte/astrocyte-associated) portions of the same axonal trunk located in the dorsal roots and dorsal columns, respectively. Dorsal spinal roots and slices of dorsal columns isolated from adult rats were studied in a sucrose gap chamber from which compound action potential and membrane potential changes could be recorded. The results indicate that the peripheral component of the afferent fibers is resistant to hypoxia as evidenced by stable action and membrane potential when O 2 in the bathing medium was completely replace with N 2 for periods up to 2 h. In contrast, the axons become sensitive to hypoxia as they project through the dorsal columns as evidenced by rapid reduction in action potential amplitude accompanied by membrane depolarization when O 2 is replaced by N 2 . This differential response to hypoxia, observed on the same axon branches but over CNS vs. PNS trajectories, suggests that differences related to the extracellular environment or in axo-glial organization in dorsal root vs. dorsal column may confer different degrees of susceptibility to anoxia.