Blood flow restriction training attenuates stroke-induced hippocampal ferroptosis, synaptic damage, and cognitive impairment via upregulating SIRT1 pathway.

Cognitive impairment is a common consequence of stroke that significantly impacts patients' quality of life. Blood flow restriction (BFR) training has emerged as a potential method for enhancing cognition, though its mechanisms remain unclear. Ferroptosis plays a critical role in post-stroke cognitive impairment, with silent information regulator 2 homolog 1 (SIRT1), a protein involved in ferroptosis regulation, being closely associated with this process in the central nervous system. This study aimed to investigate whether BFR training could inhibit stroke-induced ferroptosis via the SIRT1 pathway. A rat stroke model was developed through middle cerebral artery occlusion (MCAO), and BFR training was applied. Cognitive function was assessed using the Y-maze and Novel Object Recognition Test (NORT). Hippocampal morphology and synaptic integrity were evaluated with hematoxylin-eosin and Golgi staining. Western blotting and immunohistochemistry were used to measure SIRT1, synaptic markers, and ferroptosis-related proteins. MCAO rats exhibited significant synaptic damage, cognitive impairment, and ferroptosis, indicated by dysregulated ferroptosis proteins, disrupted iron homeostasis, and increased lipid peroxidation. BFR training alleviated these changes, improving synaptic damage and cognitive function. In contrast, SIRT1 inhibition worsened these effects, partially reversing the benefits of BFR training. These results suggest that BFR training mitigates hippocampal ferroptosis, synaptic damage, and cognitive impairment in stroke rats, partially through upregulation of the SIRT1 pathway.