Proteasome Inhibition Promotes Functional Recovery After Peripheral Nerve Reperfusion Injury

Abstract

Backgrounds: The proteasome degrades NF-kappa B blocking protein (I-kappa B) and activates NF-kappa B that plays as a key transcriptional factor to regulate inflammatory factors that are involved in the tissue reperfusion injury. This study was designed to assess whether the proteasome inhibitor can attenuate peripheral nerve ischemia/reperfusion (I/R) injury and consequently promote motor functional recovery after ischemic insult. Methods: Rat sciatic nerves were exposed to 2 hour of ischemia followed by various periods of reperfusion. Rats were administered either proteasome inhibitor (bortezomib) or phosphate-buffered saline 30 minutes before reperfusion start. Results were evaluated using a walking track test, and an isolated muscle contraction test, and by muscle weight, and histology. Results: Bortezomib treatment induced an earlier improvement in sciatic functional index and a more rapid restoration of contractile force and wet weight of extensor digitorum longus muscle. Bortezomib reduced early axonal degeneration and promoted regeneration. Conclusion: This study indicates that bortezomib; a proteasome inhibitor, is effective at promoting the functional recovery of reperfused peripheral nerve. The proteasome inhibition may play a role as one of the clinical strategy in the peripheral nervous system I/R injury with further understanding its mechanism of action.