Artikel
Soft alginate hydrogel alters scar formation and promotes locomotor recovery after spinal cord injury in a rat hemimyelonectomy model
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Veröffentlicht: | 4. Juni 2012 |
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Gliederung
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Objective: Regeneration after spinal cord injury (SCI) is very limited, since secondary cellular events enlarge the lesion and lead to impenetrable scar formation. Both restoration of the cellular pool by transplantation and provision of a suitable matrix for axonal extension through the lesion represent concepts to enhance a functional regeneration. We have introduced a novel alginate that promoted a substantial outgrowth of neurites and neurons in vitro. The purpose of the present study was to assess the effects of alginate hydrogel on locomotor recovery in rats after SCI in a hemimyelonectomy model.
Methods: 42 adult Wistar-rats weighing 210–230 g underwent a laminectomy at the level of Th9/10 and a left sided hemimyelonectomy of 2–4 mm length. The cavity was filled with alginate in the therapy group or left unfilled in the control group. The animals were examined at weekly intervals to assess the functional locomotor recovery using the open field test (Basso-Beattie-Bresnahan BBB), Louisville Swim Scale (LSS) and narrow beam walking. In 10 animals, DiI-crystals were inserted in the precentral area to accomplish an anterograde neuronal labeling and axonal tracing. The animals were sacrificed after 6 months and the lesion site processed for HE staining and immunohistochemistry (GFAP, GAP 43, β-III-Tubulin, IBA 1).
Results: Alginate was partially degraded in vivo. We observed β-III-tubulin and GAP-43 labelled neurites in fragments found directly in the lesion and at the immediate vicinity to the spinal cord tissue. Sprouting neurites were randomly oriented. Neither in the alginate nor in the control group DiI-labeled axons were observed that passed the lesion. In the control group lesions were filled with excess of fibrous connective tissue (fibrous scar), whereas in the alginate group no scarring was seen. From an early time point, the animals in the alginate group scored higher in the BBB (12,06±3,4 vs 10.31±2.5, p=0,038), LSS (9,4±2,7 vs. 4,6±1,3 p=0.0059) tests.
Conclusions: β-III-tubulin and GAP 43-labeled neurites in fragments of alginate indicate that alginate provides an adhesive surface for regenerating spinal cord neurons in vivo. However, axons did not transverse the graft. Alginate inhibits the formation of connective tissue scar. Lack of GFAP labelled astrocytes and microglia depicts also the absence of glial scar formation in the therapy group. To allow for axonal reconnections, directional modifications of the alginate construct are under development.