{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:00:10Z","timestamp":1790362810117,"version":"4.1.0"},"reference-count":79,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tikomed AB, Sweden","award":["78\/2018-PR"],"award-info":[{"award-number":["78\/2018-PR"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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\u00ae, 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\u00ae 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\u00ae) has beneficial effects on sTBI metabolic damages. Due to the absence of adverse effects in humans, ILB\u00ae represents a promising therapeutic agent for the treatment of sTBI patients.<\/jats:p>","DOI":"10.3390\/antiox9090850","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T09:10:09Z","timestamp":1599729009000},"page":"850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Low Molecular Weight Dextran Sulfate (ILB\u00ae) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat"],"prefix":"10.3390","volume":"9","author":[{"given":"Giacomo","family":"Lazzarino","sequence":"first","affiliation":[{"name":"UniCamillus-Saint Camillus International University of Health Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-9955","authenticated-orcid":false,"given":"Angela Maria","family":"Amorini","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, Via S. Sofia 97, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"Barnes","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK"},{"name":"Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Bruce","sequence":"additional","affiliation":[{"name":"Tikomed AB, 26303 Viken, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Mordente","sequence":"additional","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of the Sacred Heart of Rome, Largo F. Vito 1, 00168 Rome, Italy"},{"name":"Department of Laboratory Sciences and Infectious Disease, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5917-7279","authenticated-orcid":false,"given":"Giuseppe","family":"Lazzarino","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, Via S. Sofia 97, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina Di","family":"Pietro","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK"},{"name":"Neurotrauma and Ophthalmology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-0895","authenticated-orcid":false,"given":"Barbara","family":"Tavazzi","sequence":"additional","affiliation":[{"name":"UniCamillus-Saint Camillus International University of Health Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"},{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of the Sacred Heart of Rome, Largo F. Vito 1, 00168 Rome, Italy"},{"name":"Department of Laboratory Sciences and Infectious Disease, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Belli","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK"},{"name":"Neurotrauma and Ophthalmology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Logan","sequence":"additional","affiliation":[{"name":"Axolotl Consulting Ltd., Droitwich, Worcestershire WR9 0JS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.23736\/S0390-5616.18.04532-0","article-title":"Epidemiology of severe traumatic brain injury","volume":"62","author":"Iaccarino","year":"2018","journal-title":"J. Neurosurg. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1111\/trf.15171","article-title":"Management of moderate and severe traumatic brain injury","volume":"59","author":"Abdelmalik","year":"2019","journal-title":"Transfusion"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"574","DOI":"10.23736\/S0390-5616.18.04462-4","article-title":"Standard of care, controversies, and innovations in the medical treatment of severe traumatic brain injury","volume":"62","author":"Scerrati","year":"2018","journal-title":"J. Neurosurg. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12974-016-0555-1","article-title":"The effect of concomitant peripheral injury on traumatic brain injury pathobiology and outcome","volume":"13","author":"McDonald","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1007\/s00701-014-2127-4","article-title":"Clinical applications of intracranial pressure monitoring in traumatic brain injury: Report of the Milan consensus conference","volume":"156","author":"Stocchetti","year":"2014","journal-title":"Acta Neurochir."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1605215","article-title":"Trial of decompressive craniectomy for traumatic intracranial hypertension","volume":"375","author":"Hutchinson","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"450","DOI":"10.2310\/6650.2001.33790","article-title":"Early onset of lipid peroxidation after human traumatic brain injury: A fatal limitation for the free radical scavenger pharmacological therapy?","volume":"49","author":"Cristofori","year":"2001","journal-title":"J. Investig. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.wneu.2019.07.039","article-title":"A review of the molecular mechanisms of traumatic brain injury","volume":"131","author":"Ladak","year":"2019","journal-title":"World Neurosurg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.expneurol.2015.03.020","article-title":"Astrocyte roles in traumatic brain injury","volume":"275","author":"Burda","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"222","DOI":"10.3389\/fnmol.2019.00222","article-title":"Silencing of A20 aggravates neuronal death and inflammation after traumatic brain injury: A potential trigger of necroptosis","volume":"12","author":"Bao","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_11","unstructured":"Lorente, L., Mart\u00edn, M.M., P\u00e9rez-Cejas, A., Gonz\u00e1lez-Rivero, A.F., Argueso, M., Ramos, L., Sol\u00e9-Viol\u00e1n, J., C\u00e1ceres, J.J., Jim\u00e9nez, A., and Garc\u00eda-Mar\u00edn, V. (2019). Serum caspase-3 levels during the first week of traumatic brain injury. Med. Intensiva."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1227\/01.NEU.0000156715.04900.E6","article-title":"Cerebral oxidative stress and depression of energy metabolism correlate with severity of diffuse brain injury in rats","volume":"56","author":"Tavazzi","year":"2005","journal-title":"Neurosurgery"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kumar Sahel, D., Kaira, M., Raj, K., Sharma, S., and Singh, S. (2019). Mitochondrial dysfunctioning and neuroinflammation: Recent highlights on the possible mechanisms involved in traumatic brain injury. Neurosci. Lett., 710.","DOI":"10.1016\/j.neulet.2019.134347"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1089\/neu.2019.6439","article-title":"Hypertension exacerbates cerebrovascular oxidative stress induced by mild traumatic brain injury: Protective effects of the mitochondria-targeted antioxidative peptide ss-31","volume":"36","author":"Czigler","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1089\/neu.2018.6266","article-title":"Testosterone administration after traumatic brain injury reduces mitochondrial dysfunction and neurodegeneration","volume":"36","author":"Carteri","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s12028-009-9328-3","article-title":"Detectable levels of cytochrome C and activated caspase-9 in cerebrospinal fluid after human traumatic brain injury","volume":"12","author":"Darwish","year":"2010","journal-title":"Neurocrit. Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.3892\/mmr.2017.7040","article-title":"Lutein protects against severe traumatic brain injury through anti-inflammation and antioxidative effects via ICAM-1\/Nrf-2","volume":"16","author":"Tan","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.freeradbiomed.2018.01.031","article-title":"Deletion of NADPH oxidase 4 reduces severity of traumatic brain injury","volume":"117","author":"Ma","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3389\/fnmol.2019.00202","article-title":"EK7 regulates NLRP3 inflammasome activation and neuroinflammation post-traumatic brain injury","volume":"12","author":"Chen","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kerr, N., Lee, S.W., Perez-Barcena, J., Crespi, C., Iba\u00f1ez, J., Bullock, M.R., Dietrich, W.D., Keane, R.W., and de Rivero Vaccari, J.P. (2018). Inflammasome proteins as biomarkers of traumatic brain injury. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0210128"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s00401-018-1944-6","article-title":"The complexity of neuroinflammation consequent to traumatic brain injury: From research evidence to potential treatments","volume":"137","author":"Semple","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.bbadis.2016.01.023","article-title":"Metabolic, enzymatic and gene involvement in cerebral glucose dysmetabolism after traumatic brain injury","volume":"1862","author":"Amorini","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1227\/01.NEU.0000280002.41696.D8","article-title":"Temporal window of metabolic brain vulnerability to concussions: Mitochondrial-related impairment\u2014Part I","volume":"61","author":"Vagnozzi","year":"2007","journal-title":"Neurosurgery"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9189","DOI":"10.1038\/s41598-017-09587-2","article-title":"Fusion or fission: The destiny of mitochondria in traumatic brain injury of different severities","volume":"7","author":"Lazzarino","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.freeradbiomed.2014.01.032","article-title":"Neuroglobin expression and oxidant\/antioxidant balance after graded traumatic brain injury in the rat","volume":"69","author":"Lazzarino","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1227\/01.NEU.0000255525.34956.3F","article-title":"Temporal window of metabolic brain vulnerability to concussions: Oxidative and nitrosative stresses\u2014Part II","volume":"61","author":"Tavazzi","year":"2007","journal-title":"Neurosurgery"},{"key":"ref_27","first-page":"1286","article-title":"Temporal window of metabolic brain vulnerability to concussion: A pilot 1H-magnetic resonance spectroscopic study in concussed athletes\u2014part III","volume":"62","author":"Vagnozzi","year":"2008","journal-title":"Neurosurgery"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3232","DOI":"10.1093\/brain\/awq200","article-title":"Assessment of metabolic brain damage and recovery following mild traumatic brain injury: A multicentre, proton magnetic resonance spectroscopic study in concussed patients","volume":"133","author":"Vagnozzi","year":"2010","journal-title":"Brain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1089\/neu.1999.16.903","article-title":"Changes of cerebral energy metabolism and lipid peroxidation in rats leading to mitochondrial dysfunction after diffuse brain injury","volume":"16","author":"Vagnozzi","year":"1999","journal-title":"J. Neurotrauma"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2119\/molmed.2013.00153","article-title":"The molecular mechanisms affecting N-acetylaspartate homeostasis following experimental graded traumatic brain injury","volume":"20","author":"Amorini","year":"2014","journal-title":"Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"658786","DOI":"10.1155\/2012\/658786","article-title":"Development of an inflammation-associated colorectal cancer model and its application for research on carcinogenesis and chemoprevention","volume":"2012","author":"Tanaka","year":"2012","journal-title":"Int. J. Inflamm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.toxlet.2019.08.012","article-title":"Critical role of toll-like receptor 4 (TLR4) in dextran sulfate sodium (DSS)-Induced intestinal injury and repair","volume":"315","author":"Shi","year":"2019","journal-title":"Toxicol. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/imm.13093","article-title":"Upregulation of PD-1 follows tumour development in the AOM\/DSS model of inflammation-induced colorectal cancer in mice","volume":"158","author":"Yassin","year":"2019","journal-title":"Immunology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.1600-6143.2005.01186.x","article-title":"Low molecular weight dextran sulfate: A strong candidate drug to block IBMIR in clinical islet transplantation","volume":"6","author":"Johansson","year":"2006","journal-title":"Am. J. Transplant."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1097\/TP.0000000000002425","article-title":"Open randomized multicenter study to evaluate safety and efficacy of low molecular weight sulfated dextran in islet transplantation","volume":"103","author":"Lundgren","year":"2019","journal-title":"Transplantation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1161\/01.RES.83.3.287","article-title":"Importance of E-selectin for firm leukocyte adhesion in vivo","volume":"83","author":"Ley","year":"1998","journal-title":"Circ. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0024-3205(98)00546-3","article-title":"Dextran sulfate inhibits E-selectin-mediated neutrophil adhesion to endotoxin-activated vascular endothelial cells","volume":"64","author":"Matsumiya","year":"1999","journal-title":"Life Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1097\/00001813-199710000-00011","article-title":"Prevention of peritoneal metastasis of cancer with dextran sulfate\u2014An experimental study in mice","volume":"8","author":"Hagiwara","year":"1997","journal-title":"Anticancer Drugs"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1177\/000331978603700702","article-title":"Controlled trial of combined urokinase and dextran sulfate therapy in patients with acute cerebral infarction","volume":"37","author":"Fujishima","year":"1986","journal-title":"Angiology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3171\/jns.1994.80.2.0291","article-title":"A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics","volume":"80","author":"Marmarou","year":"1994","journal-title":"J. Neurosurg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.mito.2014.09.002","article-title":"ATP\/ADP ratio, the missed connection between mitochondria and the Warburg effect","volume":"19","author":"Maldonado","year":"2014","journal-title":"Mitochondrion"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Froese, L., Batson, C., Gomez, A., Dian, J., and Zeiler, F.A. (2020). the limited impact of current therapeutic interventions on cerebrovascular reactivity in traumatic brain injury: A narrative overview. Neurocrit. Care.","DOI":"10.1007\/s12028-020-01003-4"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"528","DOI":"10.3389\/fncel.2019.00528","article-title":"Traumatic brain injuries: Pathophysiology and potential therapeutic targets","volume":"13","author":"Ng","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1089\/neu.2007.0481","article-title":"Early and sustained alterations in cerebral metabolism after traumatic brain injury in immature rats","volume":"25","author":"Casey","year":"2008","journal-title":"J. Neurotrauma"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3171\/JNS\/2008\/108\/01\/0042","article-title":"Assessment of mitochondrial impairment in traumatic brain injury using high-resolution proton magnetic resonance spectroscopy","volume":"108","author":"Signoretti","year":"2008","journal-title":"J. Neurosurg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.1074\/jbc.M116.726752","article-title":"Mitochondrial O-GlcNAc transferase (mOGT) regulates mitochondrial structure, function, and survival in HeLa cells","volume":"292","author":"Sacoman","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Akella, N.M., Ciraku, L., and Reginato, M.J. (2019). Fueling the fire: Emerging role of the hexosamine biosynthetic pathway in cancer. BMC Biol., 17.","DOI":"10.1186\/s12915-019-0671-3"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.pep.2015.11.001","article-title":"Purification and characterization of aspartate N-acetyltransferase: A critical enzyme in brain metabolism","volume":"119","author":"Wang","year":"2016","journal-title":"Protein Expr. Purif."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1042\/BJ20111179","article-title":"Determinants of the enzymatic activity and the subcellular localization of aspartate N-acetyltransferase","volume":"441","author":"Tahay","year":"2012","journal-title":"Biochem. J."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lazzarino, G., Amorini, A.M., Signoretti, S., Musumeci, G., Lazzarino, G., Caruso, G., Pastore, F.S., di Pietro, V., Tavazzi, B., and Belli, A. (2019). Pyruvate dehydrogenase and tricarboxylic acid cycle enzymes are sensitive targets of traumatic brain injury induced metabolic derangement. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225774"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1134\/S0006297918070040","article-title":"The regulatory role of NAD in human and animal cells","volume":"83","author":"Kulikova","year":"2018","journal-title":"Biochem. Mosc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1016\/j.bbapap.2016.06.014","article-title":"NAD+ metabolism: Bioenergetics, signaling and manipulation for therapy","volume":"1864","author":"Yang","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1089\/ars.2019.7803","article-title":"Metabolic responses to reductive stress","volume":"32","author":"Xiao","year":"2020","journal-title":"Antioxid. Redox Signal"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.ejphar.2017.10.048","article-title":"Nicotinamide prevents sweet beverage-induced hepatic steatosis in rats by regulating the G6PD, NADPH\/NADP+ and GSH\/GSSG ratios and reducing oxidative and inflammatory stress","volume":"818","author":"Gutman","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.jns.2017.02.043","article-title":"Mitochondrial dysfunction\u2013Silent killer in cerebral ischemia","volume":"375","author":"Bakthavachalam","year":"2017","journal-title":"J. Neurol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.brainres.2016.02.007","article-title":"Mitochondrial specific therapeutic targets following brain injury","volume":"1640","author":"Yonutas","year":"2016","journal-title":"Brain Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.redox.2018.03.005","article-title":"NADPH oxidases in traumatic brain injury-Promising therapeutic targets?","volume":"16","author":"Ma","year":"2018","journal-title":"Redox Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"113310","DOI":"10.1016\/j.expneurol.2020.113310","article-title":"Microglia and macrophage metabolism in CNS injury and disease: The role of immunometabolism in neurodegeneration and neurotrauma","volume":"329","author":"Devanney","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1089\/neu.2013.3102","article-title":"The presence and role of iron in mild traumatic brain injury: An imaging perspective","volume":"31","author":"Nisenbaum","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Di Pietro, V., Yakoub, K.M., Caruso, G., Lazzarino, G., Signoretti, S., Barbey, A.K., Tavazzi, B., Lazzarino, G., Belli, A., and Amorini, A.M. (2020). Antioxidant therapies in traumatic brain injury. Antioxidants, 9.","DOI":"10.3390\/antiox9030260"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1002\/jnr.23848","article-title":"Microstructural and microglial changes after repetitive mild traumatic brain injury in mice","volume":"95","author":"Robinson","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s11010-005-9081-7","article-title":"Evaluating the effect of sulphated polysaccharides on cyclosporine a induced oxidative renal injury","volume":"287","author":"Josephine","year":"2006","journal-title":"Mol. Cell Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.ijbiomac.2018.12.261","article-title":"Antioxidant activities of sulfated pumpkin polysaccharides","volume":"126","author":"Chen","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Presa, F.B., Marques, M.L.M., Viana, R.L.S., Nobre, L.T.D.B., Costa, L.S., and Rocha, H.A.O. (2018). The protective role of sulfated polysaccharides from green seaweed udotea flabellum in cells exposed to oxidative damage. Mar. Drugs, 16.","DOI":"10.3390\/md16040135"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2542950","DOI":"10.1155\/2017\/2542950","article-title":"Effect of content of sulfate groups in seaweed polysaccharides on antioxidant activity and repair effect of subcellular organelles in injured HK-2 cells","volume":"2017","author":"Ma","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.bbi.2017.04.012","article-title":"Transforming growth factor-beta 1 signaling regulates neuroinflammation and apoptosis in mild traumatic brain injury","volume":"64","author":"Patel","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s10719-016-9744-5","article-title":"RGTA\u00ae or ReGeneraTing Agents mimic heparan sulfate in regenerative medicine: From concept to curing patients","volume":"34","author":"Barritault","year":"2017","journal-title":"Glycoconj. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1097\/TP.0b013e3181890593","article-title":"Low molecular weight dextran sulfate is well tolerated in humans and increases endogenous expression of islet protective hepatocyte growth factor","volume":"86","author":"Schmidt","year":"2008","journal-title":"Transplantation"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6537","DOI":"10.1523\/JNEUROSCI.22-15-06537.2002","article-title":"Overexpression of HGF retards disease progression and prolongs life span in a transgenic mouse model of ALS","volume":"22","author":"Sun","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"13700","DOI":"10.1074\/jbc.M707551200","article-title":"Hepatocyte growth factor is a novel stimulator of glucose uptake and metabolism in skeletal muscle cells","volume":"283","author":"Perdomo","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ijbiomac.2018.11.104","article-title":"Attenuation of oxidative stress induced mitochondrial dysfunction and cytotoxicity in fibroblast cells by sulfated polysaccharide from Padina gymnospora","volume":"124","author":"Vasantharaja","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1002\/mnfr.200700127","article-title":"Beneficial effects of sulfated polysaccharides from Sargassum wightii against mitochondrial alterations induced by Cyclosporine A in rat kidney","volume":"51","author":"Josephine","year":"2007","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1007\/s10571-015-0323-2","article-title":"Low-molecular-weight fucoidan attenuates mitochondrial dysfunction and improves neurological outcome after traumatic brain injury in aged mice: Involvement of Sirt3","volume":"36","author":"Wang","year":"2016","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1089\/neu.2013.2965","article-title":"Correlations between blood-brain barrier disruption and neuroinflammation in an experimental model of penetrating ballistic-like brain injury","volume":"31","author":"Cunningham","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.3171\/jns.1996.85.6.1113","article-title":"Magnetic resonance imaging-monitored acute blood-brain barrier changes in experimental traumatic brain injury","volume":"85","author":"Marmarou","year":"1996","journal-title":"J. Neurosurg."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.npep.2003.12.003","article-title":"Neurogenic inflammation is associated with development of edema and functional deficits following traumatic brain injury in rats","volume":"38","author":"Nimmo","year":"2004","journal-title":"Neuropeptides"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.lfs.2015.01.013","article-title":"Ellagic acid prevents cognitive and hippocampal long-term potentiation deficits and brain inflammation in rat with traumatic brain injury","volume":"124","author":"Farbood","year":"2015","journal-title":"Life Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.3892\/etm.2014.1840","article-title":"Progesterone protects blood-brain barrier function and improves neurological outcome following traumatic brain injury in rats","volume":"8","author":"Si","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ultrasmedbio.2009.08.006","article-title":"Molecules of various pharmacologically-relevant sizes can cross the ultrasound-induced blood-brain barrier opening in vivo","volume":"36","author":"Choi","year":"2010","journal-title":"Ultrasound Med. Biol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/9\/850\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:08:45Z","timestamp":1760177325000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/9\/850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,10]]},"references-count":79,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["antiox9090850"],"URL":"https:\/\/doi.org\/10.3390\/antiox9090850","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,10]]}}}