Ethyl pyruvate shields the brain from oxidative damage: a Keap1-Nrf2-dependent mechanism in subarachnoid hemorrhage

Early brain damage (EBI) is a serious consequence of subarachnoid hemorrhage (SAH). It has been demonstrated that ethyl pyruvate (EP) reduces the early brain damage brought on by SAH. This study investigates the role of the kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in the protective effects of EP on SAH-induced early brain injury.

In this study, we examined the effects of EP on brain damage in a rat model of SAH, including SAH grading, brain water content measurement, neurological function scoring, reactive oxygen species (ROS) levels, and apoptosis. Additionally, we analyzed the involvement of the Keap1-Nrf2 pathway using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Nrf2 knockdown was performed to assess its impact on the therapeutic effects of EP in SAH.

EP treatment significantly alleviated SAH-induced brain damage, including reducing brain water content, ROS levels, and apoptosis, while improving neurological function scores. Furthermore, EP modulated the Keap1-Nrf2 pathway by decreasing Keap1 expression and increasing Nrf2 and HO-1 expression in the brain. Nrf2 knockdown attenuated the protective effects of EP, indicating that Nrf2 activation plays a crucial role in EP's neuroprotective effects.

EP alleviates oxidative stress and neuronal damage following SAH by regulating the Keap1-Nrf2 signaling pathway. These results demonstrate EP's potential as a treatment approach that shows promise for enhancing patient outcomes in SAH.