The Potential Therapeutic Approaches to Improve Peripheral Nerve Functional Recovery from Injury PDF Download

Author: Kuang-Ching Chris Tseng
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Languages : en
Pages : 167

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Book Description
"Traumatic peripheral nerve crush injuries contribute a great deal of morbidity in patients and little improvement has been made in the treatment of these injuries in many years. Diagnosis and treatment of traumatic peripheral nerve damage suffer from a lack of means of accurately diagnosing the reasons for loss of nerve function and a lack of means of enhancing the time course of repair in injuries in which nerve function is lost for reasons other than axonal transection. In the current work, we demonstrate that administration of erythropoietin (EPO) shortens the time course of recovery after experimental crush injury to the mouse sciatic nerve. We found that systemic EPO administration maintained more myelinated axons at the site of injury in vivo following sciatic nerve crush. In vitro, EPO treatment promotes myelin formation and protects myelin from the effects of nitric oxide exposure in co-cultures of Schwann cells and dorsal root ganglion (DRG) neurons. These results suggested local EPO application might also be effective in promoting functional recovery, which would avoid potential systemic side effects of systemic EPO administration. We therefore developed a novel local treatment for peripheral nerve injury of EPO delivered in a fibrin glue matrix at the site of injury. Local delivery was as effective as systemic EPO administration, and thus may provide a potentially useful approach to enhancing recovery in peripheral nerve injuries. We also demonstrate that a single administration of 4-aminopyridine (4-AP), which enables impulse conduction in demyelinated axons, transiently restores function and allows identification of injuries in which axons are intact but not functional. We further demonstrate that repeated 4-AP administration markedly improves the time course of recovery from crush injuries in the peripheral nerve as determined by behavioral and electophysiological analyses. Equal or greater efficacy is provided by localized delivery of slow-release formulations of 4-AP at the lesion site. In addition, we provide biochemical and ultrastructural evidence to show that repeated systemic 4-AP delivery and localized slow-release delivery enhance remyelination after injury. Thus, we provide a single therapeutic approach that addresses critical issues in diagnosing peripheral nerve injury and enhancing repair, and provides the first pharmacological approach to enhancing myelin repair. As 4-AP is already used in the clinic for treatment of multiple sclerosis, our approaches are highly suitable for rapid translation from the laboratory to clinical analysis"--Pages v-vi.