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Effects of axon degeneration on oligodendrocyte lineage cells: dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis.

ABSTRACT: Wallerian degeneration in the dorsal columns (DC) after spinal cord injury (SCI) is associated with microglial activation and prolonged oligodendrocyte (OL) apoptosis that may contribute to demyelination and dysfunction after SCI. But, there is an increase in OL lineage cells after SCI that may represent a reparative response, and there is evidence for remyelination after SCI. To assess the role of axonal degeneration per se in OL apoptosis and proliferation, we cut the L2-S2 dorsal roots producing massive axonal degeneration and microglial activation in the DC, and found no evidence of OL loss or apoptosis. Rather, the numbers of OL-lineage cells positive for NG2 and APC (CC1) increased, and BrdU studies suggested new OL formation. We then tested contusion SCI (cSCI) that results in comparable degeneration in the DC rostral to the injury, microglial activation, and apoptosis of DC OLs by eight days. NG2+ cell proliferation and oligodendrogenesis was seen as after rhizotomy. The net result of this combination of proliferation and apoptosis was a reduction in DC OLs, confirming earlier studies. Using an antibody to oxidized nucleic acids, we found rapid and prolonged RNA oxidation in OLs rostral to cSCI, but no evidence of oxidative stress in DC OLs after rhizotomy. These results suggest that signals associated with axonal degeneration are sufficient to induce OL proliferation, and that secondary injury processes associated with the central SCI, including oxidative stress, rather than axonal degeneration per se, are responsible for OL apoptosis.

SUBMITTER: Sun F

PROVIDER: S-EPMC3045846 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Effects of axon degeneration on oligodendrocyte lineage cells: dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis.

Sun Fang F Lin Chien-Liang Glenn CL McTigue Dana D Shan Xiu X Tovar C Amy CA Bresnahan Jacqueline C JC Beattie Michael S MS

Glia 20100801 11

Wallerian degeneration in the dorsal columns (DC) after spinal cord injury (SCI) is associated with microglial activation and prolonged oligodendrocyte (OL) apoptosis that may contribute to demyelination and dysfunction after SCI. But, there is an increase in OL lineage cells after SCI that may represent a reparative response, and there is evidence for remyelination after SCI. To assess the role of axonal degeneration per se in OL apoptosis and proliferation, we cut the L2-S2 dorsal roots produc ...[more]

PMID: 20607865

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Project description:BackgroundSelective dorsal rhizotomy (SDR) is an irreversible surgical procedure involving the division of selected sensory nerve roots, followed by intensive physiotherapy. The aim is to improve function and quality of life in children with cerebral palsy and a Gross Motor Function Classification System (GMFCS) level of II or III (walks with or without assistive devices, respectively). We assessed gross motor function before and after SDR and postoperative quality of life in a study commissioned by NHS England.MethodsWe did a prospective observational study in five hospitals in England who were commissioned to perform SDR on children aged 3-9 years with spastic diplegic cerebral palsy. The primary outcome was score changes in the 66-item Gross Motor Function Measure (GMFM-66) and seven domains of the Cerebral Palsy Quality of Life Questionnaire ([CP-QoL] social wellbeing and acceptance, feelings about functioning, participation and physical health, emotional wellbeing and self-esteem, access to services, family health, and pain and impact of disability) from before to 24 months after SDR.FindingsFrom Sept 4, 2014, to March 21, 2016, 137 children underwent SDR. The mean age was 6·0 years (SD 1·8). The mean GMFM-66 score increased after SDR with an annual change of 3·2 units (95% CI 2·9 to 3·5, n=137). Of the seven CP-QoL domains, five showed significant improvements over time: feelings about functioning mean annual change 3·0 units (95% CI 2·0 to 4·0, n=133), participation and physical health 3·9 units (2·5 to 5·3, n=133), emotional wellbeing and self-esteem 1·3 units (0·2 to 2·3, n=133), family health 2·0 units (0·7 to 3·3, n=132), and pain and impact of disability -2·5 units (-3·9 to -1·2, n=133). 17 adverse events were reported in 15 children, of which none were severe and 15 (88%) resolved.InterpretationSDR improved function and quality of life in the 24 months after surgery in children with cerebral palsy classified as GMFCS levels II and III. On the basis of these findings, an interim national policy decision was made that SDR would be funded for eligible children in England from 2018.FundingNational Institute for Health and Care Excellence, National Institute for Health Research Biomedical Research Centre, NHS England.

Dataset Information

Effects of axon degeneration on oligodendrocyte lineage cells: dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis.

Publications

Effects of axon degeneration on oligodendrocyte lineage cells: dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis.

Similar Datasets

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