EntireAxon: Deep learning deciphers four distinct patterns of axonal degeneration

Different axonal degeneration (AxD) patterns have been described depending on the biological condition. Until now, it remains unclear whether they are restricted to one specific condition or can occur concomitantly. Here, we present a novel microfluidic device in combination with a deep learning tool, the EntireAxon, for the high-throughput analysis of AxD. We evaluated the progression of AxD in an in vitro model of hemorrhagic stroke and observed that axonal swellings preceded axon fragmentation. We further identified four distinct morphological patterns of AxD (granular, retraction, swelling, and transport degeneration) that occur concomitantly. These findings indicate a morphological heterogeneity of AxD under pathophysiologic conditions. The newly developed microfluidic device along with the EntireAxon deep learning tool enable the systematic analysis of AxD but also unravel a so far unknown intricacy in which AxD can occur in a disease context.