Bone marrow mononuclear cells and lithium salts: combined therapy in the treatment of sciatic nerve reversible demyelination.

GONZALO PIÑERO; VANINA USACH; PAULA A, SOTO; PAULA V. MONJE; CLARA P. SETTON

CABA

Congreso; The role of Glia in Health and Disease of the Nervous System; 2017

Lithium salts have been the conventional pharmacological treatment for bipolar and major depressive disorders for over six decades. Additional benefits of lithium therapy include neuroprotective, anti-inflammatory, and anti-apoptotic effects, which have been exploited to treat central nervous system trauma and chronic neurodegenerative diseases. In the peripheral nervous system, it has been shown that lithium administration can foster functional recovery and remyelination after injury. Evidence from in vitro studies has been provided, indicating that lithium enhances Schwann cell (SC) proliferation and myelin gene expression. We particularly performed a comprehensive study of the bioactivity, specificity, and reversibility of lithium?s action on the growth, survival, proliferation and differentiation of cultured Schwann cells. Also, we analyzed basal lamina and myelin formation in SC-neuron cultures. Bone marrow mononuclear cells (BMMC) constitute a heterogeneous population with potential to promote tissue regeneration. For this reason, this cell type has recently become a therapeutic alternative to mesenchymal stem cells, as culture is not required and phenotypic transformations can be hence avoided. In order to assess the effect of bone marrow cell transplantation in peripheral nerve demyelination-remyelination process, we have used two models of Wallerian degeneration: sciatic nerve ligation as an irreversible model and sciatic nerve crush as a reversible one. In both models, systemically transplanted BMMC spontaneously migrated to and remained in the injured nerve for as long as 60 days post injury (dpi). In the reversible model, once the cells arrived at the ipsilateral nerve, some of them colocalized with SC markers. Also, BMMC were shown to exert a beneficial effect on regeneration and remyelination and prevent hyperalgesia induced by sciatic nerve crush. Based on our results and bibliographical evidence, in the present work we combined these two potential treatments. After sciatic nerve crush, animals received an intravenous transplantation of BMMC and orally administered LiCl. Fourteen days post injury, axonal regeneration, remyelination and functional recovery were analyzed.