Tulated that when we inoculated Japanese white EW-7197 web rabbits with 2.5 mg of a BBG mixture (GM1 21 PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/20116414 , GD1a 40 , GD1b 16 , GT1b 19 ; CronassialTM) according to the protocol by Kusunoki et al,66) at the least some rabbits could possibly create flaccid paralysis or ataxia linked with anti-GD1a or -GD1b antibodies because the mixture contained 0.5 mg of GM1, 1 mg of GD1a or 0.four mg of GD1b. When we began our animal experiments in 1998, I was extremely skeptical as to no matter whether the rabbits would create muscle weakness. Surprisingly, all 13 rabbits inoculated together with the ganglioside mixture created flaccid paralysis.26) Limb weakness progressed for four to 13 days (median, five days) following onset, indicating acute onset (Fig. three). A few of the rabbits began to recover spontaneously, suggesting a monophasic course with the illness as shown in GBS sufferers. Unexpectedly, all the diseased rabbits created higher titers of IgG anti-GM1 antibodies, but not anti-GD1a antibodies. The antibody titers did not differ beforeNo. 7]Anti-ganglioside antibody-mediated neuropathiesGMGalactose GlucoseN -Acetylgalactosamine N -Acetylneuraminic acidL-Glycero -D-manno -heptoseCeramidePhosphoethanolamine 3-Deoxy-D-manno -2-octulosonic acid Glucosamine or 2,3-Diamino-dideoxy-D-glucoseGM1-like lipo-oligosaccharideOuter coreInner coreLipid AFig. two. Carbohydrate mimicry between gangliosides and Campylobacter jejuni lipo-oligosaccharide. The terminal tetrasaccharide of GM1-like lipo-oligosaccharide is identical to that of GM1 (shown by dashed lines). (Modified from ref. 179) with permission in the American Association of Immunologists.)Fig. three. Characteristic findings of the acute motor axonal neuropathy rabbit model. (A) Rabbit with flaccid limb weakness induced by sensitization with Campylobacter jejuni lipo-oligosaccharide. Its body is splayed, all extremities extended, head on the floor not sitting upright inside the usual compact, hunched posture. (B) Longitudinal section in the cauda equina. The nodes of Ranvier are stained selectively with protein G (arrowheads). Scale bar, ten . (C) Electron micrograph of a nerve fiber with macrophage infiltration. A macrophage [M] occupies the periaxonal space among the atrophic axon [A] and surrounding myelin sheath, which seems nearly standard. Scale bar, five . (D) Wallerian-like degeneration of nerve fibers within a paralyzed rabbit killed 39 days following onset. Sciatic nerve cross-section with toluidine blue stain. Myelin ovoids developed by Wallerian-like degeneration of myelinated fibers are present (arrowheads). Scale bar, 10 . (Reproduced from ref. 183) with permission from John Wiley Sons, Inc.)N. YUKI[Vol. 88,and after the disease onset, but high affinity antibodies were detected only at the illness onset.67) This suggested that high affinity of anti-GM1 antibodies was important for the disease improvement. In contrast, none with the 10 rabbits inoculated with keyhole limpet hemocyanin and total Freund’s adjuvant alone developed anti-GM1 antibodies and flaccid paralysis. We started inoculating rabbits with SygenTM (isolated GM1) when a number of rabbits created IgG anti-ganglioside antibodies and acute flaccid paralysis.26) Nine of 11 rabbits developed IgG anti-GM1 antibodies and acute flaccid paralysis. Pathological findings in the rabbit peripheral nerves have been predominantly Wallerian-like degeneration with neither lymphocytic infiltration nor demyelination. GM1 is expressed in both central and peripheral nervous systems, however the pathological changes are se.
