Effect of CTLA-4 Inhibition on Inflammation and Apoptosis After Spinal Cord Injury.

Abstract

Spinal cord injury (SCI) encompasses various pathological processes, notably neuroinflammation and apoptosis, both of which play significant roles. CTLA-4, a well-known immune molecule that suppresses T cell-mediated immune responses, is a key area of research and a focal point for targeted therapy development in treating tumors and autoimmune disorders. Despite its prominence, the impact of CTLA-4 inhibition on inflammation and apoptosis subsequent to SCI remains unexplored. This study aimed to investigate the influence of CTLA-4 on SCI. A weight-drop technique was used to establish a rat model of SCI. To examine the safeguarding effect of CTLA-4 on the restoration of motor function in rats with SCI, the Basso-Beattie-Bresnahan (BBB) scale and inclined plane test were employed to assess locomotion. Neuronal degeneration and apoptosis were assessed using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) and Fluoro-Jade B labeling, respectively, and the activity of microglial cells was examined by immunofluorescence. To evaluate the impact of CTLA4 on SCI, the levels of inflammatory markers were measured. After treatment with the CTLA-4 inhibitor ipilimumab, the rats showed worse neurological impairment and more severe neuroinflammation after SCI. Furthermore, the combination therapy with ipilimumab and durvalumab after SCI had more pronounced effects than treatment with either inhibitor alone. These findings indicate that CTLA-4 contributes to neuroinflammation and apoptosis after SCI, presenting a promising new therapeutic target for this traumatic condition.