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Antioxidant Therapies in Traumatic Brain Injury
Open AccessArticle

Low Molecular Weight Dextran Sulfate (ILB®) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat

1
UniCamillus-Saint Camillus International University of Health Sciences, Via di Sant’Alessandro 8, 00131 Rome, Italy
2
Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, Via S. Sofia 97, 95123 Catania, Italy
3
National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK
4
Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
5
Tikomed AB, 26303 Viken, Sweden
6
Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of the Sacred Heart of Rome, Largo F. Vito 1, 00168 Rome, Italy
7
Department of Laboratory Sciences and Infectious Disease, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
8
Neurotrauma and Ophthalmology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
9
Axolotl Consulting Ltd., Droitwich, Worcestershire WR9 0JS, UK
*
Authors to whom correspondence should be addressed.
These Authors equally contributed to this work.
Antioxidants 2020, 9(9), 850; https://doi.org/10.3390/antiox9090850
Received: 28 July 2020 / Revised: 6 September 2020 / Accepted: 8 September 2020 / Published: 10 September 2020
Traumatic brain injury (TBI) is the leading cause of death and disability in people less than 40 years of age in Western countries. Currently, there are no satisfying pharmacological treatments for TBI patients. In this study, we subjected rats to severe TBI (sTBI), testing the effects of a single subcutaneous administration, 30 min post-impact, of a new low molecular weight dextran sulfate, named ILB®, at three different dose levels (1, 5, and 15 mg/kg body weight). A group of control sham-operated animals and one of untreated sTBI rats were used for comparison (each group n = 12). On day 2 or 7 post-sTBI animals were sacrificed and the simultaneous HPLC analysis of energy metabolites, N-acetylaspartate (NAA), oxidized and reduced nicotinic coenzymes, water-soluble antioxidants, and biomarkers of oxidative/nitrosative stress was carried out on deproteinized cerebral homogenates. Compared to untreated sTBI rats, ILB® improved energy metabolism by increasing ATP, ATP/ adenosine diphosphate ratio (ATP/ADP ratio), and triphosphate nucleosides, dose-dependently increased NAA concentrations, protected nicotinic coenzyme levels and their oxidized over reduced ratios, prevented depletion of ascorbate and reduced glutathione (GSH), and decreased oxidative (malondialdehyde formation) and nitrosative stress (nitrite + nitrate production). Although needing further experiments, these data provide the first evidence that a single post-injury injection of a new low molecular weight dextran sulfate (ILB®) has beneficial effects on sTBI metabolic damages. Due to the absence of adverse effects in humans, ILB® represents a promising therapeutic agent for the treatment of sTBI patients. View Full-Text
Keywords: severe traumatic brain injury; low molecular weight dextran sulfate; mitochondrial dysfunction; energy metabolism; N-acetylaspartate; nicotinic coenzymes; oxidative/nitrosative stress; ascorbate; reduced glutathione (GSH); HPLC severe traumatic brain injury; low molecular weight dextran sulfate; mitochondrial dysfunction; energy metabolism; N-acetylaspartate; nicotinic coenzymes; oxidative/nitrosative stress; ascorbate; reduced glutathione (GSH); HPLC
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Lazzarino, G.; Amorini, A.M.; Barnes, N.M.; Bruce, L.; Mordente, A.; Lazzarino, G.; Pietro, V.D.; Tavazzi, B.; Belli, A.; Logan, A. Low Molecular Weight Dextran Sulfate (ILB®) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat. Antioxidants 2020, 9, 850.

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