PMID:14507967

Citation	Dong, H, Fazzaro, A, Xiang, C, Korsmeyer, SJ, Jacquin, MF and McDonald, JW (2003) Enhanced oligodendrocyte survival after spinal cord injury in Bax-deficient mice and mice with delayed Wallerian degeneration. J. Neurosci. 23:8682-91
Abstract	Mechanisms of oligodendrocyte death after spinal cord injury (SCI) were evaluated by T9 cord level hemisection in wild-type mice (C57BL/6J and Bax+/+ mice), Wlds mice in which severed axons remain viable for 2 weeks, and mice deficient in the proapoptotic protein Bax (Bax-/-). In the lateral white-matter tracts, substantial oligodendrocyte death was evident in the ipsilateral white matter 3-7 mm rostral and caudal to the hemisection site 8 d after injury. Ultrastructural analysis and expression of anti-activated caspase-3 characterized the ongoing oligodendrocyte death at 8 d as primarily apoptotic. Oligodendrocytes were selectively preserved in Wlds mice compared with C57BL/6J mice at 8 d after injury, when severed axons remained viable as verified by antereograde labeling of the lateral vestibular spinal tract. However, 30 d after injury when the severed axons in Wlds animals were already degenerated, the oligodendrocytes preserved at 8 d were lost, and numbers were then equivalent to control C57BL/6J mice. In contrast, oligodendrocyte death was prevented at both time points in Bax-/- mice. When cultured oligodendrocytes were exposed to staurosporine or cyclosporin A, drugs known to stimulate apoptosis in oligodendrocytes, those from Bax-/- mice but not from Bax+/+ or Bax+/- mice were resistant to the apoptotic death. In contrast, the three groups were equally vulnerable to excitotoxic necrosis death induced by kainate. On the basis of these data, we hypothesize that the Wallerian degeneration of white matter axons that follows SCI removes axonal support and induces apoptotic death in oligodendrocytes by triggering Bax expression.
Links	PubMed
Keywords	Animals; Apoptosis/genetics; Axons/pathology; Axotomy; Cell Count; Cell Death; Cell Survival/drug effects; Cell Survival/genetics; Cells, Cultured; Disease Models, Animal; Disease Progression; Enzyme Inhibitors/pharmacology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Neurologic Mutants; Necrosis; Neurotoxins/pharmacology; Oligodendroglia/cytology; Oligodendroglia/drug effects; Oligodendroglia/physiology; Proto-Oncogene Proteins/deficiency; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins c-bcl-2; Spinal Cord Injuries/pathology; Spinal Cord Injuries/physiopathology; Time Factors; Wallerian Degeneration/genetics; Wallerian Degeneration/pathology; bcl-2-Associated X Protein
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