Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury

Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury（SCI） and is currently in clinical trials.In our continuing efforts to improve Schwann cell transplantation strategies,we sought to determine the combined effects of Schwann cell transplantation with macrophage depletion.Since macrophages are major inflammatory contributors to the acute spinal cord injury,and are the major phagocytic cells,we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after SCI.To test this hypothesis,rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or not.In rat subjected to macrophage depletion,liposomes filled with clodronate were intraperitoneally injected at 1,3,6,11,and 18 days post injury.Rats not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered saline.Schwann cells were transplanted 1 week post injury in all rats.Biotinylated dextran amine（BDA） was injected at thoracic level 5 to evalute axon regeneration.The Basso,Beattie,and Bresnahan locomotor test,Gridwalk test,and sensory test using von Frey filaments were performed to assess functional recovery.Immunohistochemistry was used to detect glial fibrillary acidic protein,neurofilament,and green fluorescent protein（GFP）,and also to visulize BDA-labelled axons.The GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained slides.The numbers of BDA-positive axons were also quantified.At 8 weeks after Schwann cell transplantation,there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation alone.These changes were not associated,however,with improved Schwann cell survival,axon growth,or locomotor recovery.Although combining Schwann cell transplantation with macrophage depletion does improve histopathology of the injury site,the effect on axon growth and behavioral recovery appears no better than what can be achieved with Schwann cell transplants alone.

Schwann cells and fibronectin treating lesioned spinal cord of adult rats

Objective: To determine whether Schwann cells (SCs) and fibronectin (FN) support the growth of damaged axons and their conductive function. Methods: Thirty adult Sprague Dawley (SD) rats were randomized into 3 groups (n=10), and the following grafts: both SCs and FN, FN, and basal medium were implanted respectively into the lumbar of spinal cords hemisected at vertebra T 12 . Results: At 6 weeks postoperation, the latencies of spinal cord evoked potential (SCEP) P 1 wave in the three groups were 1.57 ms, 1.84 ms, and 2.03 ms, respectively. The differences between SCs/FN group and the other two groups were statistically significant. The number of regenerated axons in SCs/FN group was significantly greater than that in FN group. The number of survival neurons in L 4 and L 5 left dorsal root ganglia (DRG) in SCs/FN group was significantly greater than that in the rest two groups respectively. The latencies of P 1 wave were significantly correlated with axon counts in both SCs/FN and FN groups. Conclusions: SCs/FN grafted to the hemisected lumbar of spinal cords can produce robust axon regeneration and promote partial repair of their conduction. Surface recording of SCEP technique has been proved to be a reliable and less traumatic method for assessment of recovery of afferent conduction in hemisected spinal cord.