AIM2 Promotes Neuronal Apoptosis Through NF-κB Activation in an OxyHb-Induced In Vitro Subarachnoid Hemorrhage

Background: Subarachnoid hemorrhage (SAH) induces early brain injury (EBI) characterized by neuronal apoptosis, inflammation, and neurological dysfunction, yet the underlying mechanisms remain incompletely understood. Although absent in melanoma 2 (AIM2) has been implicated in post-SAH pathology, its role in neuronal injury remains unclear. Methods: Transcriptomic analyses of Gene Expression Omnibus (GEO) datasets (GSE36791 and GSE73378) were performed to investigate the association between AIM2 and nuclear factor κB (NF-κB)-related signaling. An oxyhemoglobin (OxyHb)-induced in vitro SAH model, Aim2 knockdown, and Rela co-silencing experiments were used to evaluate neuronal apoptosis, viability, and NF-κB activation. In vivo validation was performed in SAH brain tissues. Results: Transcriptomic analyses showed a positive association between AIM2 expression and NF-κB signaling. In OxyHb-treated neurons, AIM2 expression and p65 phosphorylation were increased, accompanied by enhanced neuronal apoptosis and reduced viability. Aim2 knockdown attenuated NF-κB activation, reduced neuronal apoptosis, and improved cell viability, whereas co-silencing of Aim2 and Rela exerted stronger neuroprotective effects. Aim2 silencing showed limited effects on pyroptosis-related responses, and in vivo analyses further supported a positive association between AIM2 expression and NF-κB activation after SAH. Conclusions: AIM2 contributes to OxyHb-induced neuronal apoptosis, at least in part, through NF-κB signaling. These findings provide new insight into the molecular mechanisms underlying EBI after SAH.