distal nerves from the site of injury, which were separated from their cell bodies in the brain stem. Waller described the disintegration of myelin, which he referred to as "medulla", into separate particles of various sizes. The degenerating axons formed droplets that could be stained, thus allowing for studies of the course of individual nerve fibres. Axonal degeneration Although most injury responses include a calcium influx signaling to promote resealing of severed parts, axonal injuries initially lead to acute axonal degeneration (AAD), which is rapid separation of the proximal (the part nearer the cell body) and distal ends within 30 minutes of injury. After separation, dystrophic bulb structures form at both terminals and the transected membranes are sealed. A brief latency phase occurs in the distal segment during which it remains electrically excitable and structurally intact. Degeneration follows with swelling of the axolemma, and eventually the formation of bead-like axonal spheroids. The process takes roughly 24 hours in the PNS, and longer in the CNS. The signaling pathways leading to axolemma degeneration are currently poorly understood. However, research has shown that this AAD process is calcium–independent. Granular disintegration of the axonal cytoskeleton and inner organelles occurs after axolemma degradation. Early changes include accumulation of mitochondria in the paranodal regions at the site of injury. Endoplasmic reticulum degrades and mitochondria swell up and eventually disintegrate. The depolymerization of microtubules occurs and is soon followed by degradation of the neurofilaments and other cytoskeleton components. The disintegration is dependent on Ubiquitin and Calpain proteases (caused by influx of calcium ion), suggesting that axonal degeneration is an active process and not a passive one as previously misunderstood. Thus the axon undergoes complete fragmentation. The rate of degradation is dependent on the type of injury and is also slower in the CNS than in the PNS. Another factor that affects degradation rate is the diameter of the axon: larger axons require a longer time for the cytoskeleton to degrade and thus take a longer time to degenerate. Myelin clearance Myelin is a phospholipid membrane that wraps around axons to provide them with insulation. It is produced by Schwann cells in the PNS, and by oligodendrocytes in the CNS. Myelin clearance is the next step in Wallerian degeneration following axonal degeneration. The cleaning up of myelin debris is different for PNS and CNS. PNS is much faster and efficient at clearing myelin debris in comparison to