Vitamin B Complex Treatment Attenuates Local Inflammation after Peripheral Nerve Injury

Abstract

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.

Effect of Vitamin B Complex Treatment on Macrophages to Schwann Cells Association during Neuroinflammation after Peripheral Nerve Injury

“…Previously, we have shown that the vitamin B complex treatment effectively promotes PNI-induced M1-to-M2 macrophage polarization and suppresses inflammation, by reducing the expression of proinflammatory and up-regulating the expression of anti-inflammatory cytokines [ 20 ]. Herewith, we address the relationship between macrophages and SCs, the most fundamental cell-to-cell interaction during the PNI-triggered neuroinflammation.…”

“…IL-10, whose up-regulation was shown from 7 up to 28 days post-injury [ 44 , 45 ], was proposed to modulate the proinflammatory cytokines expression and axonal plasticity [ 46 ]. In two different PNI models [ 42 , 43 ], the expression of IL-10 mRNA underwent gradual increase during Wallerian degeneration, while the recent results [ 20 ] imply the prevalence of macrophages expressing IL-10, which represents the M2-(anti-inflammatory)-phenotype marker [ 47 , 48 , 49 , 50 ] at the 14th dpo. Remarkably, fractions of ED1 + /IL-10 + cells in total ED1 + population were equivalent between O and OT animals.…”

“…Remarkably, fractions of ED1 + /IL-10 + cells in total ED1 + population were equivalent between O and OT animals. Moreover, some IL-10 + cells lacking ED1 immunoreactivity, with SCs-like morphology were observed as well [ 20 ]. In the present study, at the 14th dpo bulk of IL-10 immunoreactivity was detected in ED1 + M2-like-morphology macrophages, and in IL-10 + /S100 + cells, which were also abundantly present.…”

“…Vitamins of the B complex act as coenzymes in a plethora of enzymatic reactions, critically affecting vital cellular functions. Numerous studies clearly revealed therapeutic potential of the B complex vitamins in peripheral nerve recovery [ 18 , 19 , 20 ]. For example, the sciatic nerve injury has been associated to decreased levels of the vitamin B complex and vitamin B12 [ 18 ], indicating that the administration of these vitamins may improve the nerve regeneration process.…”

“…In addition, the same vitamins have been found to promote neurite outgrowth and enhance the velocity of nerve conduction in rat acrylamide-induced neuropathy [ 23 ]. In our previously published papers we have reported that treatment with vitamin B (B1, B2, B3, B5, B6, and B12) complex could improve the recovery of the motor nerve [ 19 ], and this progress was caused by effective transition from M1-proinflammatory to M2-anti-inflammatory/reparatory macrophage phenotype, followed by the inflammatory response suppression [ 20 ]. Consistently, the aim of the present study was to demonstrate whether the same B vitamins cocktail (B1, B2, B3, B5, B6, and B12) could affect the relationship between macrophages and SCs, the essential constituents of PNI-triggered processes of neuroinflammation/neuroregeneration; thus, ultimately promoting enhanced nerve repair.…”