American Society for Peripheral Nerve

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Macrophage Activation to Skeletal Muscle After Nerve Injury
Katherine Bernadette Santosa, MD; Anja G. Fuchs, PhD; Albina Jablonka-Shariff, PhD; Isaiah R Turnbull, MD, PhD; Alexandra Marie Keane, BA; Alison Kay Snyder-Warwick, MD
Washington University, Saint Louis, MO

Introduction: The skeletal muscle is a unique immunologic tissue that is particularly dynamic following muscle injury. Immune cells such as macrophages, normally few in number during physiologic conditions, are quickly recruited to the muscle following injury to assist in inflammatory and reparative processes. In response to their microenvironment, macrophages are able to change their phenotypes during these processes. Although macrophage recruitment and activation have been demonstrated in direct muscle injury models, this dynamic process has not been described in muscle after nerve injury. The goal of this study was to determine if acute nerve injury resulted in the recruitment of macrophages to the distal muscle target, and to characterize the phenotype of these activated macrophages.

Materials & Methods: Eight (n=4 per time point) adult wildtype C57BL/6 mice underwent right sciatic nerve transection without repair. At one or five days after neve injury, the animal was sacrificed, and all muscles of the hindlimb innervated by the sciatic nerve were harvested from the right injured and left uninjured sides. Following muscle digestion, total cells present in muscle after sciatic nerve injury were isolated for flow cytometry.

Results: Overall, there was a higher number of CD45+ hematopoietic cells isolated from denervated muscle than uninjured controls. Moreover, preliminary data demonstrate that there were significantly more Ly6C+F480- cells, a classic marker for monocytes, and CD206+MerTK+ cells, specific markers for macrophages, recruited to the muscle following acute nerve injury. At postoperative day 5, CD206+MerTK+ macrophages had decreased CD11c expression, suggesting activation of these immune cells.

Conclusions: Our studies demonstrate that acute nerve injury induces recruitment of macrophages to the distal target muscle. Moreover, recruited macrophages have an altered phenotype, which may suggest a functional transformation of these important inflammatory and regenerative immune cells. Further studies are ongoing to determine the functional impact of this macrophage phenotypic change on reinnervation of the muscle following acute nerve injury. Knowledge of this process may allow new therapeutic targets to improve functional recovery following nerve injury.


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