Melatonin Provides Neuroprotection Following Traumatic Brain Injury-Promoted Mitochondrial Perturbation in Wistar Rat

Abstract

Excessive mitochondrial fission has been implicated in the etiology of neuronal cell death in traumatic brain injury (TBI). In the present study, we examined the efficacy of melatonin (Mel) as a neuroprotective agent against TBI-induced oxidative damage and mitochondrial dysfunction. We assessed the impact of Mel post-treatment (10 mg/kg b.wt., i.p.) at different time intervals in TBI-subjected Wistar rats. We found that the Mel treatment significantly attenuated brain edema, oxidative damage, mitochondrial fission, and promoted mitochondrial fusion. Additionally, Mel-treated rats showed restoration of mitochondrial membrane potential and oxidative phosphorylation with a concomitant reduction in cytochrome-c release. Further, Mel treatment significantly inhibited the translocation of Bax and Drp1 proteins to mitochondria in TBI-subjected rats. The restorative role of Mel treatment in TBI rats was supported by the mitochondrial ultra-structural analysis, which showed activation of mitochondrial fusion mechanism. Mel enhanced mitochondrial biogenesis by upregulation of PGC-1α protein. Our results demonstrated the remedial role of Mel in ameliorating mitochondrial dysfunctions that are modulated in TBI-subjected rats and provided support for mitochondrial-mediated neuroprotection as a putative therapeutic agent in the brain trauma.

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Acknowledgements

Mohd Salman is a recipient of the Senior Research Fellowship from ICMR [F.No.3/1/2/4/Trauma/2009-NCD-1], and Pooja Kaushik is a recipient of the Senior Research Fellowship from University Grant Commission [F.No.-25-1/2014-15(BSR)/7-91/2017/(BSR)]. Dr. Heena Tabassum is grateful to the Department of Science and Technology, Government of India, for financial grant (DST Cognitive Science Initiative Program, sanction no. SR/CSI/PDF-76/2012). The Grant no.[2016/001070/HS)], received as Extramural Research Grant from the Science and Engineering Research Board, New Delhi, Government of India, to Prof. Suhel Parvez is also thankfully acknowledged. The Grant no.[SR/FST/LS-I/2017/05(C)] and [SR/PURSE Phase2/39 (C)] received from the Ministry of Science & Technology, Government of India, to Jamia Hamdard under DST-FIST and DST-PURSE programs are also thankfully acknowledged. The authors would like to thank Dr. Pradeep K. Rai, BD-JH FACS Academy, BD Biosciences, India for his help in flow cytometry analysis.

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MS, HT and SP designed the study. MS, PK, and HT conducted the experiments and analyzed the data. MS, HT and SP wrote the manuscript. SP and HT critically revised the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Suhel Parvez.

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All Surgical and experimental procedures were performed in accordance with the Institutional Animal Ethics Committee of Jamia Hamdard, New Delhi, India.

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Salman, M., Kaushik, P., Tabassum, H. et al. Melatonin Provides Neuroprotection Following Traumatic Brain Injury-Promoted Mitochondrial Perturbation in Wistar Rat. Cell Mol Neurobiol (2020). https://doi.org/10.1007/s10571-020-00884-5

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Keywords

  • Traumatic brain injury
  • Melatonin
  • Drp1
  • Mitochondria dysfunction
  • Neuroprotection
  • Repair