SCD1-Mediated Lipid Metabolism Alleviates Neuronal Ferroptosis in Subarachnoid Hemorrhage: Role of Oleic Acid Supplementation
Subarachnoid hemorrhage (SAH) can cause severe neuronal damage and trigger multiple cell death mechanisms, among which ferroptosis has garnered significant attention due to its dependence on lipid peroxidation. In this study, ferroptosis-related markers were found to be significantly dysregulated in an in vitro SAH model, confirming the ferroptotic phenotype of neurons under SAH conditions. Transcriptomic sequencing results indicated a marked downregulation of stearoyl-CoA desaturase 1 (SCD1), which was further validated by Western blot and immunofluorescence, demonstrating its colocalization with the neuronal marker NeuN. Functional experiments showed that overexpression of SCD1 effectively reduced ferroptosis-related markers and mitigated intracellular lipid accumulation. Additionally, supplementation with oleic acid (OA) significantly alleviated hemoglobin (Hb)-induced ferroptosis. Further lipid intervention experiments revealed that the ratio of saturated fatty acids (stearic acid, SA) to unsaturated fatty acids (OA) had a significant impact on neuronal survival. When the proportion of OA was increased (SA:OA = 1:2), ferroptosis was markedly inhibited. In conclusion, this study elucidates the close association between neuronal ferroptosis, SCD1 downregulation, and lipid metabolism dysregulation in SAH, providing novel insights into potential lipid metabolism-based therapeutic strategies for mitigating secondary injury following SAH.