Fig. 3

Schematic summary of the inflammatory process taking place in the peripheral axon. Monocyte recruitment and ROS production are common pathological mechanisms in many peripheral neuropathies of various causes. Several mechanisms take place simultaneously. Activated Schwann cells (SC) transdifferentiate to clear debris and recruit blood monocytes through the secretion of monocyte chemoattractant protein 1 (MCP-1/CCL2). In addition, repair SC and local fibroblasts express and secrete colony stimulating factor 1 (CSF1) to mobilize resident macrophages. Damage associated molecular patterns (DAMPs) also polarize macrophages. The on-site macrophages present a spectrum of phenotypes between M1-like macrophages and M2-like macrophages. Resolution of neuroinflammation (in a critical time-window) through intrinsic regulation or management of the external insult (e.g. correcting hyperglycaemia or withdrawing neurotoxins), likely results in reversible damage that only mildly affects nerve functionality. However, unresolved inflammation can cause tissue remodelling and fibrosis, severely affecting nerve function. AGE: advanced glycation end-products. ER: endoplasmic reticulum. UPR: unfolded protein response