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.

The therapeutic role of interleukin-10 after spinal cord injury.

Spinal cord injury (SCI) is a devastating condition affecting 270,000 people in the United States. A potential treatment for decreasing the secondary inflammation, excitotoxic damage, and neuronal apoptosis associated with SCI, is the anti-inflammatory cytokine interleukin-10. The best characterized effects of IL-10 are anti-inflammatory-it downregulates pro-inflammatory species interleukin-1ß (IL-1ß), interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-α, interferon-γ, matrix metalloproteinase-9, nitric oxide synthase, myeloperoxidase, and reactive oxygen species. Pro-apoptotic factors cytochrome c, caspase 3, and Bax are downregulated by IL-10, whereas anti-apoptotic factors B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X, B-cell lymphoma-extra large (Bcl-xl) are upregulated by IL-10. IL-10 also provides trophic support to neurons through the IL-10 receptor. Increased tissue sparing, functional recovery, and neuroprotection are seen with an immediate post-SCI systemic administration of IL-10. Treatment of SCI with IL-10 has been used successfully in combination with Schwann cell and olfactory glial cell grafts, as well as methylprednisolone. Minocycline, tetramethylpyrazine, and hyperbaric oxygen treatment all increase IL-10 levels in a SCI models and result in increased tissue sparing and functional recovery. A chronic systemic administration of IL-10 does not appear to be beneficial to SCI recovery and causes increased susceptibility to septicemia, pneumonia, and peripheral neuropathy. However, a localized upregulation of IL-10 has been shown to be beneficial and can be achieved by herpes simplex virus gene therapy, injection of poliovirus replicons, or surgical placement of a slow-release compound. IL-10 shows promise as a treatment for SCI, although research on local IL-10 delivery timeline and dosage needs to be expanded.