Tetramethylpyrazine protects mitochondrial function by up-regulation of TFAM and inhibition of neuronal apoptosis in a rat model of surgical brain injury

Document Type : Original Article


Department of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China


Objective(s): 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.
Materials and Methods: One hour after the occurrence of SBI, tetramethylpyrazine (TMP) was injected into the abdominal cavity of rats, and the brain was collected 48 hr 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. 
Results: After SBI, the content of TFAM on the ipsilateral side increased and reached a peak at about 48 hr. After intraperitoneal injection of TMP in rats, 48 hr after SBI, the concentration of TFAM, Bcl-2, and adenosine triphosphate (ATP) increased; the content of caspase-3, reactive oxygen species (ROS), and cerebral edema decreased; and the nerve function significantly improved. 
Conclusion: TMP inhibited cell apoptosis after SBI in rats by up-regulating TFAM and protecting brain tissues.


Main Subjects

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