Sodium butyrate attenuates early brain injury and neuronal apoptosis after subarachnoid hemorrhage in rats via GPR41/PI3K/Akt pathway

Objective Butyrate, a short-chain fatty acid produced by intestinal microbial fermentation of dietary fiber, serves as an endogenous ligand for the G protein-coupled receptors. Previous studies have confirmed the neuroprotective effects of sodium butyrate (NaB) in ischemic stroke, but its role in subarachnoid hemorrhage (SAH) remains unclear. Here, we investigated the potential therapeutic efficacy and underlying mechanisms of NaB in a rat SAH model. Methods NaB was administered intranasally 1 h post-SAH, and neurological function and neuronal apoptosis were evaluated 24 h post-SAH. Results During the early brain injury (EBI) phase after SAH, GPR41 was predominantly expressed in neuronal cells, and its expression levels increased significantly, peaking at 24 h post-SAH. NaB treatment attenuated neurological deficits after SAH, reduced brain edema, and alleviated neuronal damage and apoptosis. Furthermore, NaB elevated the levels of GPR41, phosphorylated Akt, and the antiapoptotic protein Bcl-2, while suppressing the expression of the proapoptotic protein Bax. Notably, the neuroprotective effects of NaB were partially reversed by GPR41 siRNA knockdown and pharmacological inhibition of PI3K with LY294002. Conclusions These findings suggest that NaB may mitigate EBI after SAH by inhibiting neuronal apoptosis, with the underlying mechanism potentially involving activation of the GPR41/PI3K/Akt signaling pathway.