Necroptosis inhibitor necrostatin-1 promotes cell protection and physiological function in traumatic spinal cord injury

• Nec-1 reduces ischemia lesions, inhibits inflammation and ROS after SCI.
• Nec-1 inhibits necroptosis by inhibiting RIP1/3–MLKL recruitment after SCI.
• Nec-1 inhibits apoptosis by down-regulation of Caspase 3 and Bax/Bcl-2 ratio.
• Nec-1 protects neurons, promotes functional recovery and ethological improvement.
• Nec-1 might be a potential drug with high protection effects and low toxicity for SCI.

Spinal cord injury (SCI) is a common and serious trauma which lacks efficient treatment. Inhibition of cell death in the trauma area is important for spinal cord protection during this process. In this study, necroptosis inhibitor necrostatin-1 (Nec-1) was used to treat SCI rats, to investigate the role of Nec-1 in the recovery of SCI. Nec-1 was found to reduce lesions, cytokines and reactive oxygen species (ROS), improve pathological conditions and blood supply in the spinal cord trauma area. Further study indicated that Nec-1 could inhibit necroptosis by inhibiting RIP1/3–MLKL recruitment and inhibit apoptosis by inhibiting Caspase 3 and Bax while activating Bcl-2. Ethological performance of SCI rats confirmed improvement and protection of physiological function by Nec-1. Nec-1 as a potential treatment for SCI warrants further study. To our knowledge, this is the first study on the role of Nec-1 in the treatment of traumatic SCI. Our research also found inhibition effects of Nec-1 on apoptosis, not only necroptosis – as reported by most publications.