Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (9): 1573-1582.doi: 10.4103/1673-5374.255972

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Polydatin prevents the induction of secondary brain injury after traumatic brain injury by protecting neuronal mitochondria

Li Li 1, 2, 6 , Hong-Ping Tan 3 , Cheng-Yong Liu 1 , Lin-Tao Yu 4 , Da-Nian Wei 1 , Zi-Chen Zhang 1 , Kui Lu 4 , Ke-Sen Zhao 2 , Marc Maegele 1, 5 , Dao-Zhang Cai 6 , Zheng-Tao Gu 1, 2
   

  1. 1 Department of Treatment Center for Traumatic Injuries, the Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics · Guangdong Province, Guangzhou, Guangdong Province, China
    2 Department of Pathophysiology, Southern Medical University, Guangdong Provincial Key Laboratory of Shock and Microcirculation Research, Guangzhou, Guangdong Province, China
    3 Department of Epilepsy Surgery, Guangdong Sanjiu Brain Hospital, Guangzhou, Guangdong Province, China
    4 Department of Emergency, the Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics · Guangdong Province, Guangzhou, Guangdong Province, China
    5 Department of Traumatology and Orthopedic Surgery, Cologne-Merheim Medical Center (CMMC), University Witten/Herdecke (UW/H), Campus Cologne-Merheim, Cologne, Germany
    6 Department of Orthopedics, the Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics · Guangdong Province, Guangzhou, Guangdong Province, China
  • Online:2019-09-15 Published:2019-09-15
  • Contact: Zheng-Tao Gu, PhD, guzhengtao@126.com; Dao-Zhang Cai, PhD, cdz@smu.edu.cn.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81501690 (to ZTG); the Scientific Research Staring Foundation for Talent Introduction for Southern Medical University (to MM).

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Abstract:

Polydatin is thought to protect mitochondria in different cell types in various diseases. Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury. To investigate the protective effect of polydatin after traumatic brain injury, a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults. Rat models were intra¬peritoneally injected with polydatin (30 mg/kg) or the SIRT1 activator SRT1720 (20 mg/kg, as a positive control to polydatin). At 6 hours post-traumatic brain injury insults, western blot assay was used to detect the expression of SIRT1, endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side. Flow cytometry was used to analyze neuronal mitochondrial su¬peroxide, mitochondrial membrane potential and mitochondrial permeability transition pore opened. Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy. Our results showed that after treatment with polydatin, release of reactive oxygen species in neuronal mitochondria was markedly reduced; swelling of mitochondria was alleviated; mitochondrial membrane poten¬tial was maintained; mitochondrial permeability transition pore opened. Also endoplasmic reticulum stress related proteins were inhibited, including the activation of p-PERK, spliced XBP-1 and cleaved ATF6. SIRT1 expression and activity were increased; p38 phosphorylation and cleaved caspase-9/3 activation were inhibited. Neurological scores of treated rats were increased and the mortality was reduced com¬pared with the rats only subjected to traumatic brain injury. These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria. The mechanisms may be linked to increased SIRT1 ex¬pression and activity, which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway. This study was approved by the Animal Care and Use Committee of the Southern Medical University, China (approval number: L2016113) on January 1, 2016.

Key words: nerve regeneration, traumatic brain injury, polydatin, mitochondria, endoplasmic reticulum stress, SIRT1, reactive oxygen species, p38, mitochondrial membrane potential, mitochondrial permeability transition pore, lateral fluid percussion, neural regeneration