Abstract
Erythropoietin (EPO) has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide) (PLGA) microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery.
Highlights
Despite the application of modern and sophisticated techniques in the treatment, peripheral nerve injury remains challenging to surgeons
The mechanism of EPO-mediated recovery is not fully understood, it has been demonstrated that the EPO receptor (EPOR) expressed by Schwann cells was the major target for EPO in peripheral nerve injury
By recruiting β1 integrin to the surface of Schwann cells, EPO promotes the migration of Schwann cells and facilitates the assembly of the provisional extracellular matrix in the injured peripheral nerve and improves injury recovery [2]
Summary
Despite the application of modern and sophisticated techniques in the treatment, peripheral nerve injury remains challenging to surgeons. Erythropoietin (EPO), which was best known as a hematopoietic cytokine, has recently been proven to have neuroprotective effects on the peripheral nerve system [1]. By recruiting β1 integrin to the surface of Schwann cells, EPO promotes the migration of Schwann cells and facilitates the assembly of the provisional extracellular matrix in the injured peripheral nerve and improves injury recovery [2]. The optimal dosage of EPO for the treatment of peripheral nerve injury is still unknown. No optimal duration of EPO administration was suggested in that study. It has been shown that the functional recovery of peripheral nerve was rapidly deteriorated when EPO administration was discontinued [3]. Continuous injection regime is usually advised for EPO application
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