Work

Capg Aggravates Neuroinflammatory Injury, Oxidative Stress, and Glial Activation After Subarachnoid Hemorrhage

Year: 2026

Type: article

Abstract: Subarachnoid hemorrhage (SAH) causes early brain injury characterized by oxidative stress and neuroinflammation, but the molecular mediators linking these processes remain unclear. We aimed to identify SAH-related biomarkers and determine the functional role of Capg in secondary brain injury. Public transcriptomic datasets were integrated, and LASSO, SVM-RFE, random forest, and SHAP analyses were used to prioritize candidate genes. Selected genes were validated in a mouse SAH model. The effects of Capg silencing were examined in vivo and in OxyHb-stimulated BV2 cells and primary mouse astrocytes by assessing neurological function, brain edema, blood-brain barrier disruption, glial activation, inflammatory mediators, oxidative stress, ferroptosis-related markers, and mitochondrial injury-associated proteins. CAPG, DSP, and PHGDH were identified as candidate SAH-related genes, with CAPG showing prominent upregulation. In mice, Capg silencing improved neurological function, reduced brain edema and blood-brain barrier permeability, and attenuated glial activation and neuronal injury. Capg knockdown also reduced IL-1β, IL-6, TNF-α, and IL-18, restored IL-10 expression, and alleviated oxidative stress and ferroptosis-associated alterations, as indicated by increased GPX4 and SOD1 and decreased ACSL4 expression. In OxyHb-stimulated BV2 cells, Capg silencing reduced BAX, tBID, BAK, and cleaved caspase-1 expression, supporting an association between Capg and mitochondrial injury-related inflammatory signaling. Capg is associated with oxidative stress, neuroinflammation, mitochondrial injury-related signaling, and cytokine release after SAH. Targeting Capg may help limit secondary brain injury, although its direct downstream mechanisms require further validation.

Source: Inflammation

DOI: 10.1007/s10753-026-02629-w