Antioxidative Strategy in Traumatic Brain Injury: Role of Low-Molecular-Weight Antioxidants

Year 2023, Volume: 4 Issue: 4, 573 - 594, 12.02.2024

Ibrahim Bulama , Umar Faruk Saidu , Nasiru Suleiman , Abdullahi Abbas , Yusuf Saidu , Yusuf Yakubu Nasiru Jinjiri , Lawal Bilbis

https://doi.org/10.46871/eams.1346139

Cited By: 1

Abstract

Objective: Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. This study was designed to investigate the beneficial and neuroprotective role of some Low-Molecular-Weight antioxidants (LMWA) in the treatment of TBI in albino rats.
Methods: TBI was induced in adult albino rats using the weight-drop method. A total of 70 Rats was used and were divided into 12 treatment groups, a traumatized non-treated group (TNT) and a Non-traumatized non-treated group (NTNT). There were 5 rats per group. Each of the treatment groups received 22.5 or 45 mg/kg of dimethyl sulfoxide (DMSO), Alpha Lipoic acid (ALA), Uric acid (UA), vitamin C (VC), vitamin E (VE), or Mannitol. Treatment was started 30 min after the trauma and continued for 21 days. To evaluate the functional outcomes, the modified neurological severity score (mNSS) was calculated. The antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)], and malondialdehyde (MDA) were assayed to evaluate oxidative stress (OS).
Results: At 7 days post-TBI, the antioxidant-treated groups exhibited significant (p<0.05) improvements in neurological scores compared to the traumatized non-treated group (TNT). The treated groups showed a significant (p<0.05) increase in the activities of antioxidant enzymes (SOD, CAT and GPx) and a significant (p<0.05) decrease in the concentration of MDA compared with the TNT group.
Conclusion: These promising results suggest that the use of low-molecular-weight antioxidants may be a useful neuroprotective strategy in the treatment of TBI. However, further studies should investigate the molecular mechanisms of these antioxidants on TBI pathophysiology and functional outcome.

Keywords

Traumatic brain injury, Oxidative Stress, Neurological score, Low-Molecular-Weight Antioxidants, Malondialdehyde

References

• 1. Webster KM, Sun M, Crack P, O’Brien TJ, Shultz SR, Semple BD. Inflammation in epileptogenesis after traumatic brain injury. Journal of Neuroinflammation. 2017;14(1). https//doi.org/10.1186/s12974-016-0786-1
• 2. Bogoslovsky T, Gill J, Jeromin A, Davis C, Diaz-Arrastia R. Fluid Biomarkers of Traumatic Brain Injury and Intended Context of Use. Diagnostics. 2016;6(4):37. https//doi.org/10.3390/diagnostics6040037
• 3. Luca L, Rogobete AF, Bedreag OH. Oxidative Stress and Antioxidant Therapy in Critically Ill Polytrauma Patients with Severe Head Injury. The Journal of Critical Care Medicine. 2015;1(3):83-91. https//doi.org/10.1515/jccm-2015-0014
• 4. Xiong Y, Mahmood A, Chopp M. Animal models of traumatic brain injury. Nature Reviews Neuroscience. 2013;14(2):128-142. https//doi.org/10.1038/nrn3407
• 5. Hode L, Madougou S, Fatigba HO, Hounnou P, Ebassa K, Hans Moevi AA, Assouto P. The Direct Cost of Treatment of Traumatic Brain Injury in a Sub-Saharan African Country (Benin). World Neurosurgery. 2017;99:210-213. https//doi.org/10.1016/j.wneu.2016.11.083
• 6. Pearn ML, Niesman IR, Egawa J, Sawada A, Almenar-Queralt A, Shah SB, Duckworth JL, Head BP. Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics. Cellular and Molecular Neurobiology. 2016;237(4):571-585. https//doi.org/10.1007/s10571-016-0400-1
• 7. Ma MW, Wang J, Zhang Q, Wang R, Dhandapani KM, Vadlamudi RK, Brann DW. NADPH oxidase in brain injury and neurodegenerative disorders. Molecular Neurodegeneration. 2017;12(1). https//doi.org/10.1186/s13024-017-0150-7
• 8. Jyoti A, Mishra N, Dhas Y. Ageing: Consequences of Excessive Free Radicals and Inflammation. Current Science. 2016;111(11):1787. https//doi.org/10.18520/cs/v111/i11/1787-1793
• 9. Bruschetta G, Impellizzeri D, Campolo M, Casili G, Di Paola R, Paterniti I, Esposito E, Cuzzocrea S. FeTPPS Reduces Secondary Damage and Improves Neurobehavioral Functions after Traumatic Brain Injury. Frontiers in Neuroscience. 2017;11. https//doi.org/10.3389/fnins.2017.00006
• 10. Venegoni W, Shen Q, Thimmesch AR, Bell M, Hiebert JB, Pierce JD. The use of antioxidants in the treatment of traumatic brain injury. Journal of Advanced Nursing. 2017;73(6):1331-1338. https//doi.org/10.1111/jan.13259
• 11. Szwajgier D, Borowiec K, Pustelniak K. The Neuroprotective Effects of Phenolic Acids: Molecular Mechanism of Action. Nutrients. 2017;9(5):477. https//doi.org/10.3390/nu9050477
• 12. Shahim P, Blennow K, Zetterberg H, Tegner Y. Mild traumatic brain injury is associated with increased levels of axonal injury biomarkers in blood. British Journal of Sports Medicine. 2017;1(11). https//doi.org/10.1136/bjsports-2016-097270.15
• 13. Arteaga O, Álvarez A, Revuelta M, Santaolalla F, Urtasun A, Hilario E. Role of Antioxidants in Neonatal Hypoxic–Ischemic Brain Injury: New Therapeutic Approaches. International Journal of Molecular Sciences. 2017;18(2):265. https//doi.org/10.3390/ijms18020265
• 14. Borlongan C, Acosta S, De la Pena I, Tajiri N, Kaneko Y, Lozano D, Gonzales-Portillo G. Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities. Neuropsychiatric Disease and Treatment. 2015;97. https//doi.org/10.2147/ndt.s65815
• 15. Ozdemir D, Uysal N, Gonenc S, Acikgoz O, Sonmez A, Topcu A, Ozdemir N, Duman M, Semin I, Ozkan H. Effect of melatonin on brain oxidative damage induced by traumatic brain injury in immature rats. Physiological Research. 2005:631-637. Doi.org/10.33549/physiolres.930709
• 16. Zoerle T, Carbonara M, Zanier ER, Ortolano F, Bertani G, Magnoni S, Stocchetti N. Rethinking Neuroprotection in Severe Traumatic Brain Injury: Toward Bedside Neuroprotection. Frontiers in Neurology. 2017;8. https//doi.org/10.3389/fneur.2017.00354
• 17. Karsy M, Brock A, Guan J, Taussky P, Kalani MYS, Park MS. Neuroprotective strategies and the underlying molecular basis of cerebrovascular stroke. Neurosurgical Focus. 2017;42(4). https//doi.org/10.3171/2017.1.focus16522
• 18. Stocchetti N, Taccone FS, Citerio G, Pepe PE, Le Roux PD, Oddo M, Polderman KH, Stevens RD, Barsan W, Maas AI, Meyfroidt G, Bell MJ, Silbergleit R, Vespa PM, Faden AI, Helbok R, Tisherman S, Zanier ER, Valenzuela T, Wendon J, Menon DK, Vincent J-L. Neuroprotection in acute brain injury: an up-to-date review. Critical Care. 2015;19(1). https://doi.org/10.1186/s13054-015-0887-8
• 19. Marmarou A, Foda MAA-E, Brink W van den, Campbell J, Kita H, Demetriadou K. A new model of diffuse brain injury in rats. Journal of Neurosurgery. 1994;80(2):291-300. https//doi.org/10.3171/jns.1994.80.2.0291
• 20. Schallert T, Kozlowski DA, Humm JL, Cocke RR. Use-dependent structural events in recovery of function. Adv Neurol. 1997;73:229-38. PMID: 8959217
• 21. Marklund SL. Analysis of extracellular superoxide dismutase in tissue homogenates and extracellular fluids. Oxygen Radicals in Biological Systems Part B: Oxygen Radicals and Antioxidants. 1990;260-265.https://doi.org/10.1016/0076-6879(90)86117-e
• 22. Johansson LH, Håkan Borg L. A spectrophotometric method for determination of catalase activity in small tissue samples. Analytical Biochemistry. 1988;174(1):331-336. https://doi.org/10.1016/0003-2697(88)90554-4
• 23. Ursini F, Maiorino M, Gregolin C. The selenoenzyme phospholipid hydroperoxide glutathione peroxidase. Biochimica et Biophysica Acta (BBA) – General Subjects. 1985;839(1):62-70. https://doi.org/10.1016/0304-4165(85)90182-5
• 24. Goulart M, Batoréu M, Rodrigues A, Laires A, Rueff J. Lipoperoxidation products and thiol antioxidants in chromium exposed workers. Mutagenesis. 2005;20(5):311-315. https://doi.org/10.1093/mutage/gei043
• 25. Davis AE. Mechanisms of Traumatic Brain Injury: Biomechanical, Structural and Cellular Considerations. Critical Care Nursing Quarterly. 2000;23(3):1-13. https//doi.org/10.1097/00002727-200011000-00002
• 26. Denniss RJ, Barker LA. Brain Trauma and the Secondary Cascade in Humans: Review of the Potential Role of Vitamins in Reparative Processes and Functional Outcome. Behavioral Sciences. 2023;13(5):388. https://doi.org/10.3390/bs13050388
• 27. Inci S, Özcan OE, Kilinç K. Time-Level Relationship for Lipid Peroxidation and the Protective Effect of α-Tocopherol in Experimental Mild and Severe Brain Injury. Neurosurgery. 1998;43(2):330-335. https//doi.org/10.1097/00006123-199808000-00095
• 28. Ehizuelen Ebhohimen I, Stephen Okanlawon T, Ododo Osagie A, Norma Izevbigie O. Vitamin E in Human Health and Oxidative Stress Related Diseases. Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects. 2021. https://doi.org/10.5772/intechopen.99169
• 29. Rani K. Role of Antioxidants in Prevention of Diseases. Journal of Applied Biotechnology & Bioengineering. 2017;4(1). https//doi.org/10.15406/jabb.2017.04.00091
• 30. Watanabe S, Kang D-H, Feng L, Nakagawa T, Kanellis J, Lan H, Mazzali M, Johnson RJ. Uric Acid, Hominoid Evolution, and the Pathogenesis of Salt-Sensitivity. Hypertension. 2002;40(3):355-360. https//doi.org/10.1161/01.hyp.0000028589.66335.aa
• 31. Jagroop Singh, Sukhraj Kaur, Manjinder Kaur, Manpreet Kaur Verma. The Role of Uric Acid as an Antioxidant in Selected Neurodegenerative Disease Pathogenesis. International Journal of Scientific Research in Science and Technology. 2022:239-247. https://doi.org/10.32628/ijsrst229440
• 32. Hooper DC, Scott GS, Zborek A, Mikheeva T, Kean RB, Koprowski H, Spitsin SV. Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood–CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis. The FASEB Journal. 2000;14(5):691-698. https//doi.org/10.1096/fasebj.14.5.691
• 33. Patwa J, Thakur A, Flora SJS. Alpha Lipoic Acid and Monoisoamyl-DMSA Combined Treatment Ameliorates Copper-Induced Neurobehavioral Deficits, Oxidative Stress, and Inflammation. Toxics. 2022;10(12):718. https://doi.org/10.3390/toxics10120718
• 34. Jones W, Li X, Qu Z- chao, Perriott L, Whitesell RR, May JM. Uptake, recycling, and antioxidant actions of α-lipoic acid in endothelial cells. Free Radical Biology and Medicine. 2002;33(1):83-93. htpp://doi.org/10.1016/s0891-5849(02)00862-6
• 35. Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radical Biology and Medicine. 1995;19(2):227-250. https//doi.org/10.1016/0891-5849(95)00017-r
• 36. Mei X- han, Yang Y- wen. Neuroprotective effects of α-lipoic acid against hypoxic– ischemic brain injury in neonatal rats. Tropical Journal of Pharmaceutical Research. 2017;16(5):1051. https//doi.org/10.4314/tjpr.v16i5.12
• 37. Regoli F, Winston GW. Quantification of Total Oxidant Scavenging Capacity of Antioxidants for Peroxynitrite, Peroxyl Radicals, and Hydroxyl Radicals. Toxicology and Applied Pharmacology. 1999;156(2):96-105. https//doi.org/10.1006/taap.1999.8637
• 38. Kalemci O, Aydin HE, Kizmazoglu C, Kaya I, Yılmaz H, Arda NM. Effects of Quercetin and Mannitol on Erythropoietin Levels in Rats Following Acute Severe Traumatic Brain Injury. Journal of Korean Neurosurgical Society. 2017;60(3):355-361. https//doi.org/10.3340/jkns.2016.0505.015
• 39. Yilmaz N, Dulger H, Kiymaz N, Yilmaz C, Gudu BO, Demir I. Activity of mannitol and hypertonic saline therapy on the oxidant and antioxidant system during the acute term after traumatic brain injury in the rats. Brain Research. 2007;1164:132-135. https//doi.org/10.1016/j.brainres.2007.06.01737