RESUMO
Peripheral nerve injury (PNI) triggers a complex multi-cellular response involving the injured neurons, Schwann cells (SCs), and immune cells, often resulting in poor functional recovery. The aim of this study was to investigate the effects of the treatment with vitamin B (B1, B2, B3, B5, B6, and B12) complex on the interaction between macrophages and SCs during the recovery period after PNI. Transection of the motor branch of the femoral nerve followed by reconstruction by termino-terminal anastomosis was used as an experimental model. Isolated nerves from the sham (S), operated (O), and operated groups treated with the B vitamins (OT group) were used for immunofluorescence analysis. The obtained data indicated that PNI modulates interactions between macrophages and SCs in a time-dependent manner. The treatment with B vitamins complex promoted the M1-to M2-macrophage polarization and accelerated the transition from the non-myelin to myelin-forming SCs, an indicative of SCs maturation. The effect of B vitamins complex on both cell types was accompanied with an increase in macrophage/SC interactions, all of which correlated with the regeneration of the injured nerve. Clearly, the capacity of B vitamins to modulate macrophages-SCs interaction may be promising for the treatment of PNI.
Assuntos
Inflamação/patologia , Macrófagos/patologia , Traumatismos dos Nervos Periféricos/patologia , Células de Schwann/patologia , Complexo Vitamínico B/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Comunicação Celular/efeitos dos fármacos , Nervo Femoral/efeitos dos fármacos , Nervo Femoral/patologia , Nervo Femoral/fisiopatologia , Proteína GAP-43 , Mediadores da Inflamação/metabolismo , Interleucina-10/farmacologia , Macrófagos/efeitos dos fármacos , Masculino , Traumatismos dos Nervos Periféricos/fisiopatologia , Ratos , Recuperação de Função Fisiológica/efeitos dos fármacos , Células de Schwann/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Complexo Vitamínico B/administração & dosagemRESUMO
Peripheral nerve injury (PNI) leads to a series of cellular and molecular events necessary for axon regeneration and reinnervation of target tissues, among which inflammation is crucial for the orchestration of all these processes. Macrophage activation underlies the pathogenesis of PNI and is characterized by morphological/phenotype transformation from proinflammatory (M1) to an anti-inflammatory (M2) type with different functions in the inflammatory and reparative process. The aim of this study was to evaluate influence of the vitamin B (B1, B2, B3, B5, B6, and B12) complex on the process of neuroinflammation that is in part regulated by l-type CaV1.2 calcium channels. A controlled transection of the motor branch of the femoral peripheral nerve was used as an experimental model. Animals were sacrificed after 1, 3, 7, and 14 injections of vitamin B complex. Isolated nerves were used for immunofluorescence analysis. Treatment with vitamin B complex decreased expression of proinflammatory and increased expression of anti-inflammatory cytokines, thus contributing to the resolution of neuroinflammation. In parallel, B vitamins decreased the number of M1 macrophages that expressed the CaV1.2 channel, and increased the number of M2 macrophages that expressed this channel, suggesting their role in M1/M2 transition after PNI. In conclusion, B vitamins had the potential for treatment of neuroinflammation and neuroregeneration and thereby might be an effective therapy for PNI in humans.