Journal of Neurocytology 11, 559-569 (1982) Triethyl tin-induced myelin oedema" an intermediate swelling state detected by X-ray diffraction D. A. KIRSCHNER ~ and V. S. SAPIRSTEIN 2 1Department of Neuroscience, Children's Hospital Medical Center, Boston, Mass 02115 and Department of Neuropathology, Harvard Medical School, Boston, Mass 02115, USA 2Department of Biochemistry, the Eunice Kennedy Shriver Center, Waltham, Mass 02254 and Department of Biological Chemistry, Harvard Medical School, Boston, Mass 02115, USA Received 7 December 1981; revised and accepted 16 February 1982 Summary X-ray diffraction was used to probe the effects of triethyl tin (TET) on the periodicity and amount of membrane disorientation in the lamellar myelin from respiring optic and sciatic nerves in vitro as well as from nerves of rats treated in vivo through their drinking water. The diffraction patterns show that in vitro TET at concentrations of 4-100 #M affects C,N.S. but not P.N.S. myelin structure. A planar, concentric membrane array with a 200 A period is detected in the C.N.S.; this ordered, swollen myelin contrasts with the vacuolar and vesicular structure seen in thin-sections in TET-induced oedema. No effects of short-term in vivo treatment with TET are observed in either the C. N. S. or P. N.S. The finding that carbonic anhydrase (CA) inhibitors have no effect on the TET-induced structural changes indicates that the swelling we observe is not related to a CA-dependent process. In comparison, the TET effect is prevented by replacing the mobile ions with isotonic sucrose. We conclude that TET-induced swelling in C.N.S. myelin arises from an increase in ion transport followed by obligatory fluid movement. Further, the ordered, swollen structure we detect may be an intermediate state that exists transiently in vivo in TET intoxication and that precedes the gross swelling and vacuolization usually observed. Introduction Electron microscopic studies on acute or chronic triethyl tin (TET) intoxication in adult rats (reviewed by Torack et al., 1970), adult mice (reviewed by Watanabe, 1980), the developing rat (Blaker et al., 1981), and in myelinating cultures of mouse spinal cord (Graham et al., 1975) reveal central nervous system demyelination that is characterized by a splitting of the lamellar myelin at the intraperiod line with subsequent fluid accumulation and widespread intramyelinic vacuole fgrmation. Similar effects have been reported in the peripheral nervous system after chronic TET dosage (Graham et al., 1976). Although such gross morphological changes produced by TET have been widely 0300-4864/82/040559-11503-82/0 9 1982 Chapman and Hall Ltd.