Effects of tDCS on Cognitive Function in MCAO/R Rats by Regulating Mitochondrial Autophagy Mediated by the PINK1/Parkin Signaling Pathway.

Cognitive dysfunction is a common and disabling consequence of stroke. Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique, has shown promise in rehabilitation; however, its molecular mechanisms remain unclear, and the lack of standardized stimulation parameters limits its clinical application. This study aimed to investigate the effects of tDCS with different intensities on cognitive function in rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and to elucidate the underlying mechanisms. A male Sprague-Dawley rat MCAO/R model was established, and animals were treated with varying intensities of anodal tDCS (a-tDCS). Cognitive function was assessed using the Morris water maze and a novel object recognition test, while neurological deficits were evaluated through neurological scoring and 2,3,5-triphenyltetrazolium chloride staining. Mitochondrial autophagy was examined by transmission electron microscopy, and the expression of PINK1/Parkin-mediated autophagy pathway proteins was analyzed by Western blot and immunohistochemistry. The results showed that 0.2 mA medium-intensity a-tDCS produced the most significant therapeutic effect, alleviating mitochondrial damage, reducing excessive mitochondrial accumulation, and attenuating neuronal apoptosis. Mechanistically, these effects were associated with activation of the PINK1/Parkin pathway, ultimately leading to improved learning and memory function. Mechanistically, these effects were associated with PINK1/Parkin pathway activation, and were attenuated when PINK1 was knocked down. Medium-intensity a-tDCS exerts neuroprotective effects in MCAO/R rats by enhancing mitophagy through the PINK1/Parkin signaling pathway, which providing a potential experimental basis for optimizing clinical rehabilitation strategies.