Demyelination is the main pathological hallmark of MS. There are different theories that seems underlying of this demyelination in MS. For instance, the outside-in theory where MS pathology is initiated by peripherally activated CD4+ T-lymphocytes infiltrating the CNS. Or the inside-out theory, that posits that MS autoimmunity occurs subsequently to primary CNS cytodegeneration. All in all, the underlying mechanism is poorly understood.
The study by Antonio Luchicchi and colleagues shows new evidence for the inside-out theory. Which has previously been addressed by Jeroen Geurts, chair of the dept. of Anatomy & Neurosciences at Amsterdam UMC. In the new Annals of Neurology publication, the researchers describe a number of subtle changes to the myelin that could generate the harmful inflammatory responses, referred to as blister-like swellings formed by myelin detachment from axons. The impaired adhesion of myelin can lead defective expression of glutamate receptors and tethering/adhesion molecules and other morphological alterations. The body wants to clean up these harmful substances, causing an inflammatory response. In the follow-up study, Luchicchi will investigate whether the blisters can indeed cause an inflammatory reaction.
Read the article by Antonio Luchicchi et al. Axon-myelin unit blistering as early event in MS normal appearing white matter.