Taurine attenuates neuronal ferroptosis by regulating GABAB/AKT/GSK3β/β-catenin pathway after subarachnoid hemorrhage.

Ferroptosis, characterized by lipid peroxidation and intracellular iron accumulation, has been reported to be involving in the pathophysiological of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Although taurine reportedly yields neuroprotective effects in multiple central neurological diseases and can attenuated neuron damage after stroke, its role in EBI after SAH remains unclear. The present study indicated that taurine levels in cerebrospinal fluid were significantly reduced in SAH patients, which suggested that taurine treatment after SAH could improve neurological impairment, oxidative stress, iron accumulation, BBB integrity and neuronal ferroptosis in the SAH model in vivo. Taurine could attenuate MDA levels and ROS accumulation and regulate the expression of SLC7A11 and GPX4 and the AKT/GSK3β pathway in vitro. GABA B receptor inhibition and Ly294002 could reverse the therapeutic effects of taurine and significantly downregulate the levels of p-AKT, p-GSK3β, β-catenin, SLC7A11 and GPX4. The protective effects of taurine on SLC7A11 and GPX4 expression were reversed by ICG001 treatment in vitro. Taken together, our findings revealed that taurine could improve neurological function and alleviate cerebral edema, oxidative stress and BBB disruption after SAH, which reduced neuronal ferroptosis by regulating the GABA B /AKT/GSK3β/β-catenin signaling pathway. SAH: subarachnoid hemorrhage; ROS: reactive oxygen species; GABA B : gamma aminobutyric acid type B; PI3K: phosphoinositol 3 kinase; AKT: protein kinase B; GSK3β: glucogen synthase kinase 3 bate; SLC7A11: solute carrier family 7 member 11; GSH: glutathione; GPX4: glutathione peroxidase-4; Glu: glutamate; Cys: cystine. [Display omitted] • Taurine levels in cerebrospinal fluid of SAH patients was significantly reduced. • Taurine could reduce early brain injury and ferroptosis by Akt/GSK3β/β-catenin signaling pathway in SAH. • GABA B receptors were potential upstream targets of AKT/GSK3β/β-catenin pathway regulated by taurine after SAH. [ABSTRACT FROM AUTHOR]