Vein wrapping promotes M2 macrophage polarization in a rat chronic constriction injury model

Abstract

Although the therapeutic potential of vein wrapping (VW) for recurrent compressive neuropathy has been widely reported, the mechanisms underlying this technique have not been characterized. M2 macrophages induced by interleukin-4 (IL-4) or interleukin-10 (IL-10) have an anti-inflammatory function and play an important role in peripheral nerve repair. To evaluate whether VW promotes M2 polarization, we divided chronic constriction injury (CCI) rats into untreated and VW (CCI + VW)-treated groups. Pain withdrawal thresholds in both groups were evaluated using von Frey filaments. Expression of the anti-inflammatory cytokines IL-4 and IL-10 in vein and nerve were quantified using real time polymerase chain reaction (RT-PCR), and expression of the anti-inflammatory M2 macrophage markers CD206 and arginase-1 (Arg1) after VW was assessed by RT-PCR and immunohistochemistry. To evaluate the effect of exogenous IL-4 or IL-10 on M2 macrophage-marker expression, CD11b-positive macrophages isolated from sciatic nerve were stimulated with recombinant IL-4 and IL-10. VW significantly increased the pain withdrawal threshold. IL-4 and IL-10 mRNA expression was higher in veins than in the sciatic nerve. VW significantly increased CD206 and Arg1 mRNA expression compared to the CCI group. The number of CD206- and Arg1-immunoreactive cells in nerve bundles was twofold higher in the CCI + VW than CCI group. Application of exogenous IL-4 doubled CD206 and Arg1 mRNA expression in CD11b-positive macrophages. These results show that vein-derived IL-4 potentiates the benefit of VW through the activation of M2 macrophages in the sciatic nerve. Our results may help to optimize current procedures for treating recurrent compressive neuropathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Wrapping With Basic Fibroblast Growth Factor‐Impregnated Collagen Sheet Reduces Rat Sciatic Nerve Allodynia

“…Rats ( n = 5 per group) were subjected to the von Frey test according to our previous report on postoperative days (PODs) 1, 5, 7, and 14. Following randomization and acclimation to the test cage for 1 h, the von Frey test was performed by applying a von Frey filament (Mono‐filament Kit; Smith & Nephew, Germantown, WI) to the hind paw at 90° to the plantar surface.…”

“…The ethics committees of Chiba University approved all protocols for animal studies (reference number: 30-345), which were performed according to the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals (1996 Revision). Similar to our previous study, [13][14][15] Wistar rats (male, 8 weeks old, 240-260 g; n = 104) were kept under controlled conditions in a semi-barrier housing system (12-h light/dark cycle, 21-23°C, 45-65% humidity) and maintained on a standard rodent chow diet (CRF-1; Oriental Yeast Co., Ltd., Tokyo, Japan).…”

“…Vein wrapping was first employed in the upper extremity to avoid scarring in peripheral nerve injury . Realization that vein tissue produced several trophic factors that play an important role in the relief of pain was another important milestone . These studies suggested that collagen materials supplemented with trophic factors may be promising for recurrent compressive neuropathy not amenable to autologous vein wrapping.…”

“…3,5,6,8,9 Realization that vein tissue produced several trophic factors that play an important role in the relief of pain was another important milestone. [12][13][14][15] These studies suggested that collagen materials supplemented with trophic factors may be promising for recurrent compressive neuropathy not amenable to autologous vein wrapping. Collagen materials have since been developed as an alternative to autologous veins and to similarly decrease nerve scarring and improve nerve gliding.…”

Frozen Vein Wrapping for Chronic Nerve Constriction Injury Reduces Sciatic Nerve Allodynia in a Rat Model

“…von Frey Test Rats (n = 5 per group) were subjected to the von Frey test according to our previous report [9][10][11]23]on postoperative days (PODs) 1, 3, 5, 7, and 14. Following randomization and 1-h acclimation to the test cage, the von Frey test was conducted by applying a von Frey lament (Mono-lament Kit; Smith & Nephew, Germantown, WI) to the hind paw perpendicular to the plantar surface.…”