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Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular disease with high rates of morbidity and mortality and a paucity of effective therapies. The development of early brain injury (EBI) is closely related to prognosis in SAH, and inflammation plays an important role in its pathophysiology. A previous experiment showed that ST2825, a selective inhibitor of MyD88, could alleviate EBI in vivo. However, this protective effect in vivo is affected by a variety of pathophysiology processes making the result to some extent uncertain. whether there is a coincident result in vitro ruling out the effect of other factors remains unknown, and further investigation using cultured neurons is necessary. Primary neuronal cells were cultured to construct an in vitro model of SAH. The cells were cultured and then divided into three groups: (1) a blank control group, (2) an oxygenated hemoglobin + vehicle group, and (3) an oxygenated hemoglobin + ST2825 group. In each group, apoptosis of neuronal cells along with changes in the expression of proteins including MyD88, p-JNK, p-Erk, p-p38, NFκB, Bcl-2, and P53 were measured. Results showed that after stimulating neurons with oxygenated hemoglobin, the expression of the MyD88 protein in the vehicle group increased significantly. The quantity of p-JNK, p-p38, and p-Erk also increased significantly, as did the quantity of p65 in the nucleus. Expression of the antiapoptotic protein Bcl-2 was markedly reduced, while that of the cleaved caspase-3 protein was significantly increased. In addition, in this group, the apoptosis rate of neurons was significantly increased. In the ST2825 group, the expression of p-JNK, p-p38, p-Erk, cleaved caspase-3, and p65 in the nucleus was significantly decreased, the expression of Bcl-2 was significantly increased, and the apoptosis rate of neurons was significantly reduced. The results of this study suggest that in an experimental in vitro SAH model, ST2825, a selective inhibitor of MyD88, can have a neuroprotective effect by inhibiting neuronal apoptosis mediated by the MAPK and NFκB signaling pathways, and this has a certain protective effect on EBI after SAH. [ABSTRACT FROM AUTHOR]