Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (12): 2438-2445.doi: 10.4103/1673-5374.313047

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Protein profiling identified mitochondrial dysfunction and synaptic abnormalities after dexamethasone intervention in rats with traumatic brain injury

Fei Niu1, #, Bin Zhang2, #, Jie Feng3, Xiang Mao4, Xiao-Jian Xu1, Jin-Qian Dong2, Bai-Yun Liu1, 2, 5, 6, *   

  1. 1Department of Neurotrauma, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; 2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 3Key Laboratory of Central Nervous System Injury Research, Center for Brain Tumor, Beijing Institute of Brain Disorders, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; 4Department of Neurosurgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China; 5Center for Nerve Injury and Repair, Beijing Institute of Brain Disorders, Beijing, China; 6China National Clinical Research Center for Neurological Diseases, Beijing, China
  • Online:2021-12-15 Published:2021-05-15
  • Contact: Bai-Yun Liu, MD, liubaiyun@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81771327 (to BYL), the Platform Construction of Basic Research and Clinical Translation of Nervous System Injury, China, No. PXM2020_026280_000002 (to BYL); and the Scientific Research and Cultivation Fund of Beijing Neurosurgical Institute of China, No. 2020002 (to FN).

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Abstract: Dexamethasone has been widely used after various neurosurgical procedures due to its anti-inflammatory property and the abilities to restore vascular permeability, inhibit free radicals, and reduce cerebrospinal fluid production. According to the latest guidelines for the treatment of traumatic brain injury in the United States, high-dose glucocorticoids cause neurological damage. To investigate the reason why high-dose glucocorticoids after traumatic brain injury exhibit harmful effect, rat controlled cortical impact models of traumatic brain injury were established. At 1 hour and 2 days after surgery, rat models were intraperitoneally administered dexamethasone 10 mg/kg. The results revealed that 31 proteins were significantly upregulated and 12 proteins were significantly downregulated in rat models of traumatic brain injury after dexamethasone treatment. The Ingenuity Pathway Analysis results showed that differentially expressed proteins were enriched in the mitochondrial dysfunction pathway and synaptogenesis signaling pathway. Western blot analysis and immunohistochemistry results showed that Ndufv2, Maob and Gria3 expression and positive cell count in the dexamethasone-treated group were significantly greater than those in the model group. These findings suggest that dexamethasone may promote a compensatory increase in complex I subunits (Ndufs2 and Ndufv2), increase the expression of mitochondrial enzyme Maob, and upregulate synaptic-transmission-related protein Gria3. These changes may be caused by nerve injury after traumatic brain injury treatment by dexamethasone. The study was approved by Institutional Ethics Committee of Beijing Neurosurgical Institute (approval No. 201802001) on June 6, 2018.

Key words: dexamethasone, Gria3, Maob, mass spectrometry, mitochondrial dysfunction, Ndufs2, Ndufv2, proteomics, synaptic abnormalities, traumatic brain injury

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