Certolizumab enhances spinal cord injury recovery in rats through inhibition of the TNF-α signaling pathway and neuronal apoptosis.

Abstract

Objective: Spinal cord injury (SCI), which is characterized by motor and/or sensory dysfunction, presents a significant health challenge resulting from mechanical trauma. Secondary injury, which follows the mechanical trauma and is driven by factors such as inflammation, plays a critical role in the SCI pathophysiology. Scientific evidence indicates that treatment strategies aimed at modulating inflammation during the acute phase of SCI alleviate the seconder injury. In this regard, the present study seeks to evaluate the effectiveness of certolizumab, a monoclonal antibody targeting TNF-α that is widely used in the treatment of various inflammatory diseases, in a SCI model.

Methods: In this study, Control, Trauma, and Trauma + Certolizumab groups were established, each comprising eight male rats. One hour after SCI induction, rats in the Trauma + Certolizumab group were administered 10 µg Certolizumab dissolved in saline intraperitoneally, while rats in the Control and Trauma groups received an equivalent volume of saline. After Modified Tarlov Scoring was performed on the seventh day of the experiment, all rats were sacrificed. The effects of certolizumab on neuroinflammation and apoptosis in the SCI model were evaluated using histological, biochemical, and molecular analyses of blood and tissue samples obtained from the rats.

Results: Certolizumab downregulated the expression of TNF-α, NF-κB, and IL-6. In addition, as evidenced by the TUNEL assay, Caspase-3 expression (an apoptotic marker), and Modified Tarlov Score results, certolizumab effectively suppressed inflammation-induced neural apoptosis and alleviated locomotor deficits.

Conclusion: Certolizumab treatment exerts a neuroprotective effect against secondary damage in SCI through the inhibition of neuroinflammation and apoptosis.