The neuroimmunology of degeneration and regeneration in the peripheral nervous system

Abstract

Peripheral nerves regenerate following injury due to the effective activation of the intrinsic growth capacity of the neurons and the formation of a permissive pathway for outgrowth due to Wallerian degeneration. Wallerian degeneration and subsequent regeneration are significantly influenced by various immune cells and the cytokines they secrete. Although macrophages have long been known to play a vital role in the degenerative process, recent work has pointed to their importance in influencing the regenerative capacity of peripheral neurons. In this review, we focus on the various immune cells, cytokines, and chemokines that make regeneration possible in the peripheral nervous system, with specific attention placed on the role macrophages play in this process.

Overexpression of the monocyte chemokine CCL2 in dorsal root ganglion neurons causes a conditioning-like increase in neurite outgrowth and does so via a STAT3 dependent mechanism

“…Studies on the immune consequences of nerve injury have focused on actions at or distal to the injury site, in particular the role of macrophages in Wallerian degeneration (for reviews see Bruck, 1997; DeFrancesco-Lisowitz et al, 2014). The actions of multiple immune cells in the distal nerve also may have bearing on the process of regeneration (e.g., Brown et al, 1991; Schmid et al, 2013; Vargas et al, 2010).…”

“…Injury to peripheral nerves activates an inflammatory response that plays a significant role in axonal regeneration and functional recovery (Bastien and Lacroix, 2014; DeFrancesco-Lisowitz et al, 2014; Popovich and Longbrake, 2008). In response to axotomy, both injured peripheral neuronal cell bodies and Schwann cells distal to the injury site upregulate and release the C-C class chemokine 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1; Schreiber et al, 2001; Subang and Richardson, 2001; Tanaka et al, 2004; Toews et al, 1998).…”

Microglia density decreases in the rat rostral nucleus of the solitary tract across development and increases in an age-dependent manner following denervation

“…This may explain why the robust microglia response to adult CTX across all rNTS zones, such as noted here, is accompanied by a preservation of the CT terminal fields despite temporary loss of afferent input (Reddaway et al, 2012). Microglia have been associated with peripheral nerve regeneration in other systems (DeFrancesco-Lisowitz et al, 2015) and the protective effect of microglia following adult CTX is implicated by studies which impact microglia function. Minocycline has been used to inhibit microglial inflammatory response while leaving anti-inflammatory and protective functions intact (Kobayashi et al, 2013).…”

Miconazole alleviates peripheral nerve crush injury by mediating a macrophage phenotype change through the NF‐κB pathway

“…PNI around the damaged microenvironment causes a series of local responses, which to a certain extent, affects the degenerated nerve regeneration (Freria et al, 2016). However, PNS is not completely isolated, and the injured axons trigger a complex multi-cellular response that involves multiple components (DeFrancesco-Lisowitz, Lindborg, Niemi, & Zigmond, 2015;Gaudet, Popovich, & Ramer, 2011). Wallerian degeneration is one of the most important processes involved in PNI.…”