Tetramethylpyrazine protects mitochondrial function by upregulating TFAM and alleviating nerve cell apoptosis in SBI rats

Abstract

Abstract Mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) damage and mutation is widely accepted as one of the pathological processes of neurodegenerative diseases. As an mtDNA binding protein, mitochondrial transcription factor A (TFAM) maintains the integrity of mtDNA through transcription, replication, nucleoid formation, damage perception, and DNA repair. In recent works, the overexpression of TFAM increased the mtDNA copy count, promoted mitochondrial function, and improved the neurological dysfunction of neurodegenerative diseases. The role of TFAM in neurodegenerative diseases has been well explained. However, the role of TFAM after surgical brain injury (SBI) has not been studied. In this work, we aimed to study the role of TFAM in the brain after SBI and its mechanism of action. One hour after the occurrence of SBI, tetramethylpyrazine (TMP) was injected into the abdominal cavity of rats, and the brain was collected 48 hours later for testing. The evaluation included neurobehavioral function test, brain water content measurement, immunofluorescence, western blot, TUNEL staining, FJC staining, ROS test, and ATP test. The results showed that after SBI, the content of TFAM on the ipsilateral side increased and reached a peak at about 48 h. After intraperitoneal injection of TMP in rats, 48 hours after SBI, the concentration of TFAM, Bcl-2, and ATP increased; the content of caspase-3, ROS, and cerebral edema decreased; and the nerve function significantly improved. We conclude that TMP inhibited cell apoptosis after surgical brain injury in rats by upregulating TFAM and protecting brain tissues.