Prox1 induces new lymphatic vessel formation and promotes nerve reconstruction in a mouse model of sciatic nerve crush injury.

Abstract

The peripheral nervous system lacks lymphatic vessels and is protected by the blood–nerve barrier, which prevents lymphocytes and antibodies from entering the neural parenchyma. Peripheral nerve injury results in degeneration of the distal nerve and myelin degeneration causes macrophage aggregation, T lymphocyte infiltration, major histocompatibility complex class II antigen expression, and immunoglobulin G deposition in the nerve membrane, which together result in nerve edema and therefore affect nerve regeneration. In the present paper, we show myelin expression was absent from the sciatic nerve at 7 days after injury, and the expression levels of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE‐1) and Prospero Homeobox 1 (Prox1) were significantly increased in the sciatic nerve at 7 days after injury. The lymphatic vessels were distributed around the myelin sheath and co‐localized with lymphatic endothelial cells. Prox1 induces the formation of new lymphatic vessels, which play important roles in the elimination of tissue edema as well as in morphological and functional restoration of the damaged nerve. This study provides evidence of the involvement of new lymphatic vessels in nerve repair after sciatic nerve injury.