In contrast, in the caudal end of the VLT the pathology was concentrated in the outer rim of the white matter close to the pia. There are numerous reports of demyelination and remyelination following SCI. The details vary, perhaps depending upon lesion used, time after injury and selection of areas reported on. There seems to be general agreement that the process of demyelination is slower and more protracted than following peripheral nerve injuries. The process appears to involve either break-up of the Folinic acid calcium salt pentahydrate myelin sheath and gradual engulfment by invading macrophages and/or gradual thinning of the sheath to the point where some large unmyelinated axons could be observed. Their very size makes the conclusion that these are derived from previously large myelinated axons seem reasonable. Less plausible are the claims by some authors that clusters of small unmyelinated axons were derived from previously myelinated axons. In these reports, injured Tulathromycin B spinal cords show clusters of small axons of sizes corresponding to that of unmyelinated axons; it seems unlikely that groups of myelinated axons would simultaneously lose their myelin sheaths and shrink to the size normally associated with unmyelinated axons, leaving no trace of myelin debris. It appears that remyelination of demyelinated axons at chronic stages of injury may involve both Schwann cells, invading from dorsal root ganglia close to the site of injury or immature oligodendroglia. The extent to which demyelinated axons remyelinate either as part of “normal” post injury changes or in response to local application of potentially myelinating cells such as Schwann cells, olfactory ensheathing cells or progenitor oligodendroglia is important for devising and implementing repair strategies aimed at remyelination. However, in devising such strategies it will be important to have clear evidence of what constitutes demyelinated axons and their successful remyelination. Horner and colleagues have questioned the notion that there is chronic widespread demyelination in the injured cord. In their studies injured and intact axons were differentiated after SCI and they found no evidence of demyelination of intact axons but that this only occurred in injured axons. They also found substantive endogenous remyelination of injured axons albeit this results in shortened internodes and thinner myelin to normal spinal tracts. Altogether the authors contested the idea that there is a large target population of demyelinated axons to manipulate for therapeutic improvements. We found rapid loss of axon numbers after SCI in rats with little evidence of further loss beyond one week after the injury although tissue remodelling continued for much longer. Changes to oligodendrocytes could be detected even earlier and CNPase in cords predicted very well the longer-term survival of white matter tissue. We also found evidence for continuing myelination in juvenile rats, which does not seem to have been considered in previous rat studies. These processes appeared to be arrested closer to the injury site but continued at distal levels. We found progressive decrease in pathology with time but it was still detectable up to 10 weeks after the injury. Pathological changes to axons were faster in the middle of the injury and also the clearing of myelin debris, which is likely to be due to the recruitment of macrophages to this area. Altogether it appears that there is a need for early intervention to have a significant outcome for sparing of white matter following injury, however, the exact timing for an effective intervention may of course be dependent on the injury type and model in which it is studied. Recent genome-wide association studies using clinical phenotypes have identified a large number of DNA polymorphisms that convey an increased risk for common diseases.