Simvastatin and Simvastatin-Ezetimibe Improve the Neurological Function and Attenuate the Endothelial Inflammatory Response after Spinal Cord Injury in Rat.

During a spinal cord injury (SCI), mechanical trauma rapidly leads to a blood-spinal cord barrier (BSB) disruption, neural cell damage, axonal damage, and demyelination, followed by a cascade of secondary inflammatory reactions. These inflammatory responses spread the damage to the neural cells and impair the recovery of neurological functions. In the present study, we evaluated the efficacy of simvastatin and a simvastatin-ezetimibe combination therapy in managing the endothelial inflammatory response in an SCI rat model. Adult male Sprague-Dawley rats were group-housed and SCI was induced by using the modified weight-drop method. The animals were divided into 4 groups: (1) sham group, laminectomy only (n=6); (2) no-treatment group, SCI without therapy (n=8); (3) simvastatin group (n=8), and (4) ezetimibe and simvastatin combination therapy group (n=8). A high dose (15 mg/kg) of simvastatin was given to the simvastatin group, and 10 mg/kg simvastatin and 10 mg/kg ezetimibe were given to the combination group. Neurological function was assessed using the Basso, Beattie, and Bresnahan locomotor scale score. Intercellular adhesion molecule-1 (ICAM-1) level was used as an SCI biomarker. ICAM-1 level was the highest at 72 hours after SCI in the no-treament group. The treatment groups showed significant reduction in ICAM-1 levels at 72 hours. The treatment groups, especially the combination treatment group, showed better neurological function scores. Simvastatin and simvastatin- ezetimibe all could improve the neurological function and attenuate the endothelial inflammatory response after spinal cord injury in rat.