TFAM signaling molecule alleviates mitochondrial damage of cerebral ischemia-reperfusion

In the present study, we aimed to investigate the antioxidant and therapeutic protective effects of carvacryl acetate (CAA) on Mitochondrial damage of cerebral ischemia-reperfusion through mitochondrial transcription factor A (TFAM) signaling molecules.SD rats were used to establish the middle cerebral artery occlusion (MCAO) model in vivo, and PC12 cells were stimulated with H₂O₂ in vitro. Longa neurological score and triphenyltetrazolium chloride (TTC) staining was used to observe the ischemic infarction. Transmission electron microscope (TEM) was used to observe the mitochondria. Reactive Oxygen Species/ Superoxide Dismuptase/Malondialdehyde/Adenosine Triphosphate (ROS/SOD/MDA/ATP) detection kit was used to detect. RT-qPCR was used to detect the mRNA level of target gene and mitochondrial DNA (mtDNA) copy number changes. Immunofluorescence and Western blot were used to detect the expression of protein. After oxidative stress in the MCAO model of SD rats, the neurological score increased, the volume of ischemic area of cerebral infarction increased, the morphology of nerve cells in brain tissue and PC12 cells was disordered, the mitochondria appeared vacuolated, the contents of ROS and MDA increased, and the activity of SOD decreased. Oxidative stress causes mitochondrial dysfunction, resulting in the reduction of mtDNA copy number and the decreased expression of TFAM in brain tissue nerve cells and PC12 cells, which in turn affects mitochondrial transcription biogenesis and decreases the expression of POLRMT and TFB₂M molecules. CAA promotes intracellular TFAM expression and activates its antioxidant pathway, thereby protecting mtDNA and alleviating oxidative stress and mitochondrial damage caused by MCAO in vivo and H₂O₂ stimulation in vitro. Lentivirus downregulates the expression of TFAM, and under its action, the antioxidant and mitochondrial protection effects of CAA are weakened. When TFAM was disrupted, the protective effect of CAA on mitochondria was inhibited. Compared to edaravone, a positive control, CAA exhibited similar therapeutic effects. These findings suggest that CAA alleviates CIRI through TFAM signaling pathways, offering potential therapeutic implications for ischemic stroke treatment.