K. KADOYA1, K. NGUYEN1, M. TUSZYNSKI1,2;
1Neurosciences, UCSD, LA JOLLA, CA; 2VAMC, La Jolla, CA
Environment of chronic stage of spinal cord injury (SCI) is more refractory to adult axonal growth, at least due to additional obstacles, including myelin debris and developed scar formation at lesion sites consisting of reactive astrocytes and chondroitin sulfate glycosaminoglycans (CSPGs). At the previous SFN meeting, we reported a great axonal extension from 6 months delayed NPC grafts (chronic) placed in T3 complete transection sites. But, there was a significant reduction in their number of axons, compared to 2 weeks delayed NPC grafts (subacute) placed in the same lesion. Because size of graft/lesion, presence of fibrous tissue separating the graft, and the extent of atrophy of host spinal cord were different, the undiluted effect of chronically injured spinal cord on axonal growth from NPCs remains to be clarified. To ask this question, in the present study, GFP expressing NPCs were grafted into sites of rat C4 dorsal column injury at a time point 2 weeks (subacute) or 6 months (chronic) after the initial injury. Six weeks later, lesion sites were filled with mature neurons and glia without fibrous tissue, and there was no difference of graft/lesion size in both groups. GFP-labeled, graft-derived axons emerged from the lesion site in high numbers and extended over long distances of up to 2cm. Of note, there was no significant difference in the number of emerging GFP axons in host white matter when quantified 3mm caudal and rostral to grafts. In both grafted groups, GFAP and CSPG expression around the lesion site was attenuated compared to control lesioned, non-grafted groups. In another group of subjects, we examined whether degenerating white matter in chronic SCI inhibits NPC-derived axon outgrowth. Lesions were placed in the C5 dorsal columns, and GFP expressing NPCs were micro-grafted subacutely or chronically into dorsal column sensory tract at the C4 level, where axons were undergoing Wallerian degeneration after injury. While numerous myelin debris were present from 1 week to 6 weeks after injury, clearance of much debris had occurred by 6 months. Extending axons from NPCs in this degenerating tract were in equal numbers in both groups at a point 3 mm rostral to grafts, when examined 6 weeks later, indicating that NPCs can extend axons robustly in degenerating white matter at the both of chronic and subacute stage of SCI. Collectively, these findings indicate that NPCs exhibit a remarkable ability to extend axons over chronic scar formation around injury site and through degenerating white matter.
Full Abstract at SfN 2014
Read the full story at THE SCIENTIST: Neurons Regenerate in Rat Spinal Cord