Research advances in cuproptosis during cerebral ischemia-reperfusion injury and the therapeutic potential of traditional Chinese medicine.

Cerebral ischemia-reperfusion injury (CIRI) involves oxidative stress, mitochondrial dysfunction, and various cell death mechanisms. Recently, the concept of cuproptosis has revealed that an imbalance in physiological copper (Cu) homeostasis may serve as a contributing factor to neuronal damage in CIRI. This process is characterized by Cu accumulation, proteotoxic stress, oxidative stress, and inflammatory responses. Notably, the observation that Cu chelators can attenuate this damage suggests that cuproptosis is implicated in the pathological progression of CIRI. Traditional Chinese medicine (TCM) offers the unique advantage of multi-target regulation. It shows promise in restoring metal homeostasis, clearing reactive oxygen species (ROS), protecting mitochondrial function, and inhibiting inflammation. Therefore, TCM may provide alternative insights for neuroprotective strategies targeting Cu homeostasis. In this review, we systematically summarize the molecular mechanisms of cuproptosis in CIRI and explore the potential of TCM to provide neuroprotection by targeting this pathway. Ultimately, we aim to offer fresh perspectives for the clinical prevention and management of ischemic stroke.