2. Academic Validation
  3. Ethyl pyruvate shields the brain from oxidative damage: a Keap1-Nrf2-dependent mechanism in subarachnoid hemorrhage

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

  • Brain Res. 2025 Nov 1:1866:149939. doi: 10.1016/j.brainres.2025.149939.
Mei Zhang 1,  Xiaojiao Deng 2,  Zhenfei Teng 2,  Hai Yu 2,  Zelin Hao 2,  Haisong Xu 2,  Wusi Qiu 2,  Jun Cheng 2,  Jianyue Wu 2
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China. Electronic address: [email protected].
  • 2 Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China.
PMID: 40935310 DOI: 10.1016/j.brainres.2025.149939
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

Brain injury; Ethyl pyruvate; Nuclear factor erythroid 2-related factor 2; Oxidative stress; Subarachnoid hemorrhage.

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