Intravenous Immunoglobulin (IVIg) are human IgG derived from plasma pools of healthy donors. Although there are studies in literature evaluating their effectiveness in different pathological animal models, there are no data about their possible role on Bortezomib (BTZ)-induced peripheral neuropathies. Female Wistar rats were treated following a preventive schedule (BTZ and IVIg co-treatment for 3 and 8 weeks) and a therapeutic schedule (4 weeks of BTZ treatment followed by a 4-week IVIg-BTZ cotreatment). Caudal nerve conduction velocity (NCV), plantar and dynamic tests were performed at different time points. Animals were sacrificed after 3ws (acute phase) or 8ws (chronic phase) and tissue samples (Dorsal Root Ganglias -DRG-, sciatic nerve, caudal nerve, skin) were collected for morphological, morphometrical and immunohistological analysis.In the preventive schedule, IVIg was not able to rescue caudal NCV reduction caused by BTZ neither after 3 nor after 8 weeks of co-treatment. Same results were observed in the therapeutic schedule. On the other hand, the evaluation of mechanical allodynia and cold hyperalgesia showed that IVIg injection protected from BTZ effect in both treatment schedules. Morphometric analysis evidenced that, even if not statistically significant only the preventive schedule has a tendency to protect the caudal nerve from BTZ damage. This result is consistent with the morphological evaluation of the nerve. Also, intraepidermal nerve fibers density was preserved in the preventive schedule but not in the therapeutic one. Finally, sciatic nerve and DRG macrophage infiltration levels tended to be reduced in the therapeutic schedule and were brought back to ctrl (rats not treated or injected with IVIg alone) levels in the preventive one. In conclusion, we were able to demonstrate for the first time that IVIg treatment especially used as preventive treatment option may reduce BTZ-induced neuropathic painful pointing out the possible role of inflammation in the pathogenesis of this invalidating pathology
Ballarini, E., Meregalli, C., Carozzi, V., Chiorazzi, A., Canta, A., Monza, L., et al. (2017). Ivig Effect In A Wistar Rat Model Of Bortezomib-Induced Peripheral Neuropathy. In 2017 PNS Annual Meeting Abstracts book (pp.238-239).
Ivig Effect In A Wistar Rat Model Of Bortezomib-Induced Peripheral Neuropathy
Ballarini, E;Meregalli, C;Carozzi, VA;Chiorazzi, A;Canta, AR;Monza, L;Fumagalli, G;Pozzi, E;Alberti, P;Rodriguez Menendez, V;Bossi, M;Marmiroli, PL;Cavaletti, GA
2017
Abstract
Intravenous Immunoglobulin (IVIg) are human IgG derived from plasma pools of healthy donors. Although there are studies in literature evaluating their effectiveness in different pathological animal models, there are no data about their possible role on Bortezomib (BTZ)-induced peripheral neuropathies. Female Wistar rats were treated following a preventive schedule (BTZ and IVIg co-treatment for 3 and 8 weeks) and a therapeutic schedule (4 weeks of BTZ treatment followed by a 4-week IVIg-BTZ cotreatment). Caudal nerve conduction velocity (NCV), plantar and dynamic tests were performed at different time points. Animals were sacrificed after 3ws (acute phase) or 8ws (chronic phase) and tissue samples (Dorsal Root Ganglias -DRG-, sciatic nerve, caudal nerve, skin) were collected for morphological, morphometrical and immunohistological analysis.In the preventive schedule, IVIg was not able to rescue caudal NCV reduction caused by BTZ neither after 3 nor after 8 weeks of co-treatment. Same results were observed in the therapeutic schedule. On the other hand, the evaluation of mechanical allodynia and cold hyperalgesia showed that IVIg injection protected from BTZ effect in both treatment schedules. Morphometric analysis evidenced that, even if not statistically significant only the preventive schedule has a tendency to protect the caudal nerve from BTZ damage. This result is consistent with the morphological evaluation of the nerve. Also, intraepidermal nerve fibers density was preserved in the preventive schedule but not in the therapeutic one. Finally, sciatic nerve and DRG macrophage infiltration levels tended to be reduced in the therapeutic schedule and were brought back to ctrl (rats not treated or injected with IVIg alone) levels in the preventive one. In conclusion, we were able to demonstrate for the first time that IVIg treatment especially used as preventive treatment option may reduce BTZ-induced neuropathic painful pointing out the possible role of inflammation in the pathogenesis of this invalidating pathology
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