Nature. 1973 Aug 17; 244(5416):443-4. PMID: 4582500.Abstract
Suggested By Alastair Compston and alasdair coles
Today’s hope of remyelinating therapies depends on the demonstrations that remyelination is possible in the central nervous system, that this process is mediated by the oligodendrocyte precursor, and that it is accompanied by functional improvement. This paper definitively demonstrated remyelination in the adult mammalian central nervous system, and—perhaps most importantly—showed how to identify demyelinated fibres. The investigators compressed the spinal cords of three adult cats, which causes early demyelination with retained axons; remyelination starts 3 weeks later. Their main discovery, using electron microscopy, was that the remyelinated sheath is abnormally thin and has an intermodal distance reduced by 50% compared to control fibres of the same diameter. Under the light microscope, no evidence emerged for the presence of Schwann cells, so the team concluded that oligodendrocytes had been responsible for the remyelination. These ultrastructural characteristics—reduced internode distance and inappropriately thin myelin—have become the defining features used to recognise remyelinated axons (as opposed to the partially demyelinated axons) in experimental and human pathological studies. The next important step was the demonstration that such remyelinated axons could restore function (Smith, Blakemore, and McDonald, 1979; Smith, Blakemore, and McDonald, 1981).
Suggested By Alastair Compston and alasdair coles
Today’s hope of remyelinating therapies depends on the demonstrations that remyelination is possible in the central nervous system, that this process is mediated by the oligodendrocyte precursor, and that it is accompanied by functional improvement. This paper definitively demonstrated remyelination in the adult mammalian central nervous system, and—perhaps most importantly—showed how to identify demyelinated fibres. The investigators compressed the spinal cords of three adult cats, which causes early demyelination with retained axons; remyelination starts 3 weeks later. Their main discovery, using electron microscopy, was that the remyelinated sheath is abnormally thin and has an intermodal distance reduced by 50% compared to control fibres of the same diameter. Under the light microscope, no evidence emerged for the presence of Schwann cells, so the team concluded that oligodendrocytes had been responsible for the remyelination. These ultrastructural characteristics—reduced internode distance and inappropriately thin myelin—have become the defining features used to recognise remyelinated axons (as opposed to the partially demyelinated axons) in experimental and human pathological studies. The next important step was the demonstration that such remyelinated axons could restore function (Smith, Blakemore, and McDonald, 1979; Smith, Blakemore, and McDonald, 1981).