Oleuropein Reduces Secondary Injury Pathways After Experimental Spinal Cord Injury Via HMGB1-Associated Signaling.

Abstract

OBJECTIVE: Spinal cord injury (SCI) can cause profound disability and substantial morbidity and mortality. Oleuropein (OLE) is a phenolic compound with anti-inflammatory and antioxidant effects. High mobility group box 1 (HMGB1), released extracellularly after tissue injury, can amplify inflammatory signaling. This study investigated the effects of OLE administration following experimental SCI. METHODS: Twenty-four female rats were randomly assigned to sham, SCI, and SCI+OLE groups (n=8 each). The sham group underwent T9-T10 laminectomy without SCI. In the SCI and SCI+OLE groups, SCI was induced by 30-second extradural compression with a temporary aneurysm clip. OLE was administered intraperitoneally immediately after injury and again 1 h later. Animals were euthanized 24 h after surgery. Levels of HMGB-1, NF-κB, RAGE, TLR4, and Nrf2 were measured in spinal cord tissue samples by immunohistochemistry and Western blotting. Apoptosis-related protein levels were detected by Western blot. The TUNEL assay was used to quantify apoptotic cells. Oxidative status was assessed using the total oxidant status, the total antioxidant status, and the oxidative stress index. RESULTS: Levels of HMGB1, RAGE, TLR4, and NF-κB increased after SCI, whereas OLE reduced their levels. Nrf2 expression increased after SCI and was further upregulated by OLE. OLE also significantly reduced apoptosis, as evidenced by changes in apoptosis-related protein expression. CONCLUSIONS: OLE exerted anti-apoptotic, anti-inflammatory, and antioxidant effects in this experimental SCI model, as demonstrated by analyses of spinal cord tissue and serum.

Key Findings

• Oleuropein (OLE) administration after spinal cord injury (SCI) reduced levels of HMGB1, RAGE, TLR4, and NF-κB, which are associated with inflammatory signaling.
• Nrf2 expression increased after SCI and was further upregulated by OLE treatment, indicating enhanced antioxidant response.
• OLE significantly reduced apoptosis in spinal cord tissue, as shown by changes in apoptosis-related protein expression and TUNEL assay results.

Clinical Significance

Citation

Çalış Fatih, Akkaya Enes, Evran Şevketet al.. Oleuropein Reduces Secondary Injury Pathways After Experimental Spinal Cord Injury Via HMGB1-Associated Signaling. Medeniyet medical journal. 2026-Sep-18.