BACH1 inhibition confers neuroprotection after subarachnoid hemorrhage through activation of the Nrf2 signaling pathway

Subarachnoid hemorrhage (SAH) remains one of the most severe forms of stroke, yet effective therapeutic options remain limited. The BTB domain and CNC homolog 1 (BACH1), a transcription factor widely distributed across mammalian tissues, has been implicated in regulating diverse cellular functions. Nevertheless, its role in early brain injury after SAH remains incompletely understood. In this study, we found that BACH1 expression rose rapidly and peaked at 24h after SAH. Both neurons and microglia exhibited detectable BACH1 expression. Silencing BACH1 with siRNA markedly alleviated neuroinflammation and oxidative stress, and improved neurological performance. Additionally, BACH1 suppression shifted microglial phenotypes by diminishing the M1 response and enhancing M2 polarization. Further analysis revealed that inhibiting BACH1 activated the Nrf2-dependent pathway, whereas Nrf2 depletion with ML385 diminished the protective effects associated with BACH1 knockdown. Collectively, these results identify BACH1 as a promising candidate for alleviating brain damage associated with SAH.