Modulation of VEGF and IL-2 in radiation-induced brain injury: neuroprotective effects of melatonin and ascorbic acid in rats

PURPOSE: This study investigates the neuroprotective effects of melatonin and ascorbic acid, alone and in combination, on radiation-induced brain injury, specifically focusing on vascular and immunological modulations. METHODS: Thirty-three male Wistar-Albino rats were assigned to five groups: Control (G1), Radiotherapy (RT) only (single dose 20 Gy) (G2), RT + Melatonin (20 mg/kg) (G3), RT + vitamin C (100 mg/kg) (G4), and RT + Melatonin + Vitamin C (G5). The treatments were administered intraperitoneally the day after RT. Brain tissues were evaluated 28 days post-irradiation for histopathological neural damage, vasocongestion, and immunohistochemical expression of vascular endothelial growth factor (VEGF) and interleukin-2 (IL-2). RESULTS: High-dose RT significantly increased vasocongestion and neuronal damage while suppressing VEGF expression and elevating IL-2 levels (p < 0.001). Both melatonin and ascorbic acid effectively reduced histopathological injury, maintained VEGF levels, and balanced IL-2 expression compared to the RT-only group (p < 0.05). However, combining both agents provided no significant synergistic advantage over monotherapies. Notably, single-fraction high-dose RT resulted in a marked suppression of VEGF expression, suggesting an impaired vascular synthetic capacity rather than a compensatory angiogenic response. CONCLUSION: Melatonin and ascorbic acid provide substantial neuroprotection against radiation-induced brain injury by preserving vascular integrity and modulating local immune responses. These antioxidants represent potential therapeutic strategies for minimizing RT-induced neurotoxicity.