Effect of necrostatin-1 on sciatic nerve crush injury in rat models

Abstract

Background: Necrostatin-1 (Nec-1) is an inhibitor of the receptor interacting protein (RIP)1 kinase, which acts as an inhibitor of necroptosis, a special form of necrosis. In the present study, the effect of Nec-1 on peripheral nerve injury (PNI) was investigated. Methods: The PNI model was established by inducing sciatic nerve injury. Hematoxylin–eosin and immunofluorescence staining techniques were used to assess the extent of injury to nerve fibers and necrosis of Schwann cells (SCs). Western blotting was performed to detect the expression of necroptosis-related factors (RIP1 and RIP3). The concentrations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and the oxidative stress-related enzyme malondialdehyde (MDA) were determined to indicate the degree of inflammation and oxidative stress. Results: Nec-1 could decrease the degree of peripheral nerve lesions after PNI and protect SCs and axons by inhibiting necroptosis. Furthermore, Nec-1 could reduce necroptosis by inhibiting RIP1 and effectively reduce inflammation and reactive oxygen species production at the early stage of PNI. Conclusions: Alleviation of necroptosis by Nec-1 may provide new insights into therapies for the early stages of peripheral nerve repair after PNI.