Ultrastructural evidence of myelinopathy in 5-FU-treated animals. Electron micrographs were taken from the midline transverse sections of the CC (cross-sections of the axons). (a) A representative image from a sham-treated control animal, showing normal myelinated axons; (b-f) representative images from a 5-FU-treated animal, showing multiple pathological changes of both the myelin and axonal structures. Single asterisks indicate demyelinated axons with rarefaction (that is, decreased density of the axoplasm staining possibly due to disruptions in cytoskeletal structures and organelles); double asterisks indicate an abnormal axon with partially destructed myelin sheaths; single arrows indicate inter-laminar splitting of the myelin sheaths; and double arrows indicate myelin debris. (b) Two axons with damaged myelin sheaths (asterisks), myelin debris (double arrows) and a smaller axon that seems to be detaching from its myelin sheath (single arrow) can be seen. (c) A large demyelinated axon with rarefaction of the axoplasm (asterisk) and two axons with collapsed centers and inter-laminar splitting of the myelin sheaths (arrows) can be seen, indicating on-going myelin degeneration. (d) Two large axons with completely (asterisk) or partially (double asterisks) damaged myelin can be seen, the axoplasm of which shows altered cytoskeleton and organelles. One axon has a collapsed center and inter-laminar splitting (arrow). (e) Myelin debris can be seen, possibly from a degenerating axon (double arrows) and an axon with inter-laminar splitting (arrow). (f) A demyelinated axon with rarefaction of the axoplasm and possible axonal swelling (asterisk) and two neighboring axons with inter-laminar splitting (arrows) can be seen.