Physical interactions between activated microglia and injured axons: do all contacts lead to phagocytosis?

Abstract

Axonal injury is a pathological hallmark of both head injury and inflammatory-mediated neurological disorders, including multiple sclerosis (Schirmer et al., 2013). Such axonal disruptions and/or disconnections typically result in proximal axonal segments that remain in continuity with the neuronal soma while losing contact with their distal targets. These disconnected axonal segments contribute to loss of signal transduction and overall circuit disruption, via subsequent deafferentation. Due to the disruption of anterograde transport in this cohort of axons, immunolabeling of the normally transported protein, amyloid precursor protein (APP), in post-mortem brain tissue is the most commonly used method for the visualization of the swollen end of proximal axonal segments. While proximal axonal segments remain connected to the neuronal cell body, axonal segments distal to the point of injury progress to anterograde Wallerian degeneration, forming myelin and axonal debris that negatively affect the surrounding tissue (Vargas and Barres, 2007; Mietto et al., 2015).