The Effects of Glial Cell Line-Derived Neurotrophic Factor after Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating condition affecting 270,000 people in the United States. The use of growth factors is a potential treatment for reducing secondary damage, promoting axon growth, and restoring some of the lost function post-SCI. Glial cell line-derived neurotrophic factor (GDNF) is an important growth factor, because it can affect both neurons and support cells. Here, we give an in-depth review of the previously published literature where GDNF was used to treat SCI. The effects of GDNF have been shown to decrease lesion size, improve allodynia, and regenerate axons in the central nervous system and peripheral nervous system. GDNF is necessary for early development, and lack of GDNF can lead to abnormal development of the autonomic nervous system or death. Exogenous administration of GDNF either before or immediately after SCI is most effective. Even though GDNF can be directly administered, genetically modified cells are often used as a delivery vehicle. Several different types of genetically modified cells have been used with varying success. Although GDNF is effective when used alone, it has been shown to be more effective when used in combination with other neurotrophic factors. Overall, GDNF significantly improved functional recovery, increased the number of sprouting neurons, reduced lesion size at the injury site, and had minimal adverse effects.

Immunohistochemical assessment of rat nerve isografts and immunosuppressed allografts.

OBJECTIVE: Autologous peripheral nerve grafts are commonly used clinically as a treatment for peripheral nerve injuries. However, in research using an autologous graft is not always feasible due to loss of function, which in many cases is assessed to determine the efficacy of the peripheral nerve graft. In addition, using allografts for research require the use of an immunosuppressant, which creates unwanted side effects and another variable within the experiment that can affect regeneration. The objective of this study was to analyze graft rejection in peripheral nerve grafts and the effects of cyclosporine A (CSA) on axonal regeneration. METHODS: Peripheral nerve grafts in inbred Lewis rats were compared with Sprague-Dawley (SD) rats to assess graft rejection, CSA side effects, immune responses, and regenerative capability. Macrophages and CD8+ cells were labeled to determine graft rejection, and neurofilaments were labeled to determine axonal regeneration. RESULTS: SD rats without CSA had significantly more macrophages and CD8+ cells compared to Lewis autografts, Lewis isografts, and SD allografts treated with CSA. Lewis autografts, Lewis isografts, and SD autografts had significantly more regenerated axons than SD rat allografts. Moreover, allografts in immunosuppressed SD rats had significantly less axons than Lewis rat autograft and isografts. DISCUSSION: Autografts have long been the gold standard for treating major nerve injuries and these data suggest that even though CSA is effective at reducing graft rejection, axon regeneration is still superior in autografts versus immunosuppressed allografts.