Friday, 14 June 2013

Oligodendrocyte progenitor cell injury contributes to injury

Epub: Cui et al. Oligodendrocyte Progenitor Cell Susceptibility to Injury in Multiple Sclerosis. Am J Pathol. 2013 Jun 4. doi:pii: S0002-9440(13)00334-9.

Remyelination in multiple sclerosis (MS) is often incomplete. In experimental models, oligodendrocyte progenitor cells (OPCs) rather than previously myelinating oligodendrocytes (OLs) are responsible for remyelination. This study compares the relative susceptibility of adult human OPCs and mature OLs to injury in actively demyelinating MS lesions and under in vitro stress conditions. 

In all lesions (n = 20), the relative number of mature OLs (Olig2 weak/NogoA positive) was reduced compared to control white matter (mean 38 ± 4% of control value). In 11 cases, relative OPC numbers (Olig2 strong; NogoA negative) were also decreased; in eight of these, the percentage reduction was greater for OPCs than for mature OLs. In the other nine samples, relative OPC numbers were greater than control white matter, indicating ongoing OPC migration and/or proliferation. Analysis of co-cultures with rat dorsal root ganglia neurons confirmed that OPCs were more capable of contacting and ensheathing axons than mature OLs. In isolated culture under stress conditions (withdrawal of serum/glucose and/or antioxidants), OPCs showed increased cell death and reduced process extension compared to mature OLs. Under all culture conditions, OPCs up-regulated expression of genes in the extrinsic proapoptotic pathway, and had increased susceptibility to tumor necrosis factor-induced cell death as compared to OLs. Our data suggest that susceptibility of OPCs to injury within the MS lesion environment contributes to the limited remyelination in MS.

This study is self explanatory.

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