Could Etanercept Hold Promise for Treating Spinal Cord Injuries?

After spinal cord injury, oxidative stress, inflammation, and mitochondrial dysfunction can cause neural damage that was once believed to be both immediate and irreversible. However, neuronal death is now believed to proceed over a period of several days after initial trauma, and to include cellular, molecular, and biochemical cascades, including local inflammatory responses. Tumor necrosis factor (TNF) is believed to be involved in the local production of cytokines at the site of the injury.

In a study recently published in the Asian Journal of Neurosurgery, researchers sought to assess whether the anti-TNF agent etanercept could have neuroprotective effects following spinal cord injury.

The investigators conducted their study in 54 rats, randomly assigned to undergo either skin incision (from which nonischemic spinal cord samples were obtained), spinal cord trauma followed by spinal cord sampling, or spinal cord trauma followed by immediate administration of a single dose of etanercept (at a dose of 5 mg/kg) and spinal cord sampling. Samples were obtained from the rats in each of the 3 groups at 1 hour (n = 6), 6 hours (n = 6), and 24 hours (n = 6).

The researchers found that levels of the pro-inflammatory cytokine interleukin1-beta (IL-1β) levels were lower in rats in the etanercept group at 1 hour and 6 hours after injury, and spinal tissue catalase (an antioxidative enzyme) levels were significantly higher in the etanercept group at 6 hours, versus the trauma-only group. Spinal tissue levels of TNF alpha and malondialdehyde (a lipid peroxidation product that increases immediately after spinal cord injury) were significantly lower in the etanercept group than in the trauma group at hours 1 and 6.

Histopathological grades of trauma in the etanercept group were improved versus the trauma-alone group, though the histopathological grades of the etanercept group were higher at 24 hours than they were at 6 hours. Thus, say the authors, a single dose of etanercept may not be sufficient to maintain its benefits through 24 hours post-injury.

The authors conclude that etanercept decreased TNF and IL-1β levels while increasing antioxidative enzymes at 1 hour and 6 hours, and that early administration of etanercept may help to reduce histopathological damage that occurs after spinal cord injury.

Reference

Hasturk AE, Baran C, Yilmaz ER, et al. Etanercept prevents histopathological damage after spinal cord injury in rats. Asian J Neurosurg. 2018;13(1):37-45. doi: 10.4103/ajns.AJNS_307_16.