We have previously shown that systemically administered leukemia inhibitory factor (LIF), following overhemisection spinal cord injury (SCI) in the mouse, prevents oligodendrocyte death and secondary demyelination. Here, we report that the prevention of oligodendrocyte death by LIF treatment reduces Nogo-A deposits above and below the transection site. This finding is associated with modulation of Nogo-A-dependent signaling whereby active RHOA (GTP-RhoA) id decreased and the levels of its downstream target, the phospho-Thr555-collapsin response mediator protein-2(p-Thr555-CRMP-2), are reduced in the white matter axons near the lesion. The potential for axonal growth in LIF-treated animals is enhanced through upregulation of the neurite grwoth-related molecules GAP-43 and GTP-Rac1. These findings suggest a mechanism by which exogenous LIF can promote axonal growth in the mammalian spinal cord following injury, by providing a permissive tissue environment for endogenous regrowth.
|Pages (from-to)||23 - 29|
|Number of pages||7|
|Journal||Journal of Neurodegeneration & Regeneration|
|Publication status||Published - 2008|