Remyelination of cortical lesions may not always repair

Rodriguez EG, Wegner C, Kreutzfeldt M, Neid K, Thal DR, Jürgens T, Brück W, Stadelmann C, Merkler D. Oligodendroglia in cortical multiple sclerosis lesions decrease with disease progression, but regenerate after repeated experimental demyelination. Acta Neuropathol. 2014 Feb 25. [Epub ahead of print]

Cerebral cortex shows a high endogenous propensity for remyelination. Yet, widespread subpial cortical demyelination (SCD) is a common feature in progressive multiple sclerosis (MS) and can already be found in early MS. In the present study, we compared oligodendroglial loss in SCD in early and chronic MS. Furthermore, we addressed in an experimental model whether repeated episodes of inflammatory SCD could alter oligodendroglial repopulation and subsequently lead to persistently demyelinated cortical lesions. NogoA+ mature oligodendrocytes and Olig2+ oligodendrocyte precursor cells were examined in SCD in patients with early and chronic MS, normal-appearing MS cortex, and control cortex as well as in the rat model of repeated targeted cortical experimental autoimmune encephalomyelitis (EAE). NogoA+ and Olig2+ cells were significantly reduced in SCD in patients with chronic, but not early MS. Repeated induction of SCD in rats resulted only in a transient loss of NogoA+, but not Olig2+ cells during the demyelination phase. This phase was followed by complete oligodendroglial repopulation and remyelination, even after four episodes of demyelination. Our data indicate efficient oligodendroglial repopulation in subpial cortical lesions in rats after repeated SCD that was similar to early, but not chronic MS cases. Accordingly, four cycles of experimental de- and remyelination were not sufficient to induce sustained remyelination failure as found in chronic cortical MS lesions. This suggests that alternative mechanisms contribute to oligodendrocyte depletion in chronic cortical demyelination in MS.

So you can repeatedly demyelinate a rat and it will remyelinate its grey matter, in MS it is suggested that early lesions. Likewise remyelinate but chronic (older) ones may not and some of the myelin forming precursors were reduced in the chronic lesions. At some point the repair potential becomes exhausted. However yet again we have pathologists who can’t agree. 

Cortical remyelination: a new target for repair therapies in multiple sclerosis. Chang A, Staugaitis SM, Dutta R, Batt CE, Easley KE, Chomyk AM, Yong VW, Fox RJ, Kidd GJ,Trapp BD.Ann Neurol. 2012;72(6):918-26. Endogenous remyelination of the cerebral cortex occurs in individuals with MS regardless of disease duration or chronological age of the patient

The truth is likely to be somewhere between the two. Some people will repair very well and others will not and they maybe at risk to more cognitive problems. Maybe if they used a different strain or age of rat they may have got a different result. However the commonality with the white matter is if there are not myelinating precursors in the lesions then they don’t repair as well.In rats repeated demyelination was met with repair and so in support of ProfG’s view that one of the best early repair strategies is get rid of the inflammation and the brain will repair itself.

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