Cognition, Neurology, Neurologie, Toxicology, Toxicologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Toxicologie, Toxicology, Agent alkylant, Alkylating agent, Agente alquilante, Analogue, Analog, Análogo, Antimitotique, Antimitotic, Antimitótico, Dipeptide, Dipeptides, Dipéptido, Dérivé du taxane, Taxane derivatives, Taxane derivado, Inhibiteur du protéasome, Proteasome inhibitor, Inhibidor proteasome, Pathologie du système nerveux, Nervous system diseases, Sistema nervioso patología, Platine II Complexe, Platinum II Complexes, Platino II Complejo, Traitement, Treatment, Tratamiento, Anticancéreux, Antineoplastic agent, Anticanceroso, Bortézomib, Bortezomib, Chimiothérapie, Chemotherapy, Quimioterapia, Cisplatine, Cisplatin, Cisplatino, Diffraction RX, X ray diffraction, Difracción RX, Microscopie électronique, Electron microscopy, Microscopía electrónica, Myéline, Myelin, Mielina, Paclitaxel, Pathologie du système nerveux périphérique, Peripheral nerve disease, Nervio periférico patología, Structure, Estructura, Acide boronique, Myelin structure, Peripheral neuropathy, and X-ray diffraction
Purpose: Alterations in mRNA for myelin proteins are reported in animal models of chemotherapy-induced peripheral neuropathies (CIPN); however, ultrastructural changes in aldehyde-fixed and plastic-embedded myelin are not evident by electron microscopy. Therefore, we used X-ray diffraction (XRD) to investigate more subtle changes in myelin sheath structure from unfixed nerves. Experimental design: We used in vivo chronic animal models of CIPN in female Wistar rats, administering cisplatin (CDDP 2 mg/kg, i.p. twice/week), paclitaxel (PT 10 mg/kg, i.v. once/week) or bortezomib (0.20 mg/kg, i.v. three times/week) over a total period of 4 weeks. Animal weights were monitored, and tail nerve conduction velocity (NCV) was determined at the end of the treatments to assess the occurrence of peripheral neuropathy. Sciatic nerves were collected and the myelin structure was analyzed using electron microscopy (EM) and XRD. Results: All the rats treated with the chemotherapy agents developed peripheral neuropathy, as indicated by a decrease in NCV values; however, light and electron microscopy indicated no severe pathological alterations of the myelin morphology. XRD also did not demonstrate significant differences between sciatic nerves in treated vs. control rats with respect to myelin period, relative amount of myelin, membrane structure, and regularity of membrane packing. Conclusions: These results indicate that experimental peripheral neuropathy caused by CDDP, PT, and bortezomib—which are among the most widely used chemotherapy agents—does not significantly affect the structure of internodal myelin in peripheral nerve.