Cortexin modulates OPG/RANK/RANKL and TRPC1 expression in cerebral ischemia-reperfusion injury

Biomarkers such as Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor κ-B (RANK), its ligand RANKL, and Transient Receptor Potential Canonical 1 (TRPC1) have been implicated in the neuroprotective response to neuronal injury, with their expression potentially influenced by antioxidant treatments. The objective of this study was to investigate the effects of Cortexin on the expression of these biomarkers in brain tissue following cerebral ischemia-reperfusion (I/R) injury.

Thirty-five male Wistar albino rats were divided into five groups: control, ischemia (45 minutes), I/R (7 days), I/R + 1 mg/kg Cortexin, and I/R + 2 mg/kg Cortexin. On day 8, rats were euthanized, and brain and serum samples were collected. Immunohistochemical staining was used to assess biomarker expression in brain tissue, while serum total oxidant status (TOS) and total antioxidant status (TAS) were measured using ELISA.

Oxidative stress analysis showed significantly increased TOS levels (p = 0.012; p = 0.005) and decreased TAS levels (p = 0.000; p = 0.000) in the ischemia and I/R groups compared to control. Cortexin significantly reduced TOS (p < 0.01) and increased TAS, with 2 mg/kg Cortexin producing TAS levels higher than control (p < 0.05). Immunohistochemical analysis revealed significantly elevated OPG, RANK, RANKL, and TRPC1 expression in ischemia and I/R groups (p < 0.001). Cortexin treatment significantly decreased expression of all markers (p < 0.01). No significant difference was found between ischemia and I/R groups (p > 0.05), suggesting a sustained inflammatory response.

These findings suggest that Cortexin may exert neuroprotective effects by modulating oxidative stress and biomarker expression involved in inflammation and calcium signaling.