{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:05:49Z","timestamp":1779375949871,"version":"3.53.1"},"reference-count":63,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T00:00:00Z","timestamp":1659139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tikomed AB"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In a previous study, we found that administration of ILB\u00ae, a new low molecular weight dextran sulphate, significantly improved mitochondrial functions and energy metabolism, as well as decreased oxidative\/nitrosative stress, of brain tissue of rats exposed to severe traumatic brain injury (sTBI), induced by the closed-head weight-drop model of diffused TBI. Using aliquots of deproteinized brain tissue of the same animals of this former study, we here determined the concentrations of 24 amino acids of control rats, untreated sTBI rats (sacrificed at 2 and 7 days post-injury) and sTBI rats receiving a subcutaneous ILB\u00ae administration (at the dose levels of 1, 5 and 15 mg\/kg b.w.) 30 min post-impact (sacrificed at 2 and 7 days post-injury). Additionally, in a different set of experiments, new groups of control rats, untreated sTBI rats and ILB\u00ae-treated rats (administered 30 min after sTBI at the dose levels of 1 or 5 mg\/kg b.w.) were studied for their neurocognitive functions (anxiety, locomotor capacities, short- and long-term memory) at 7 days after the induction of sTBI. Compared to untreated sTBI animals, ILB\u00ae significantly decreased whole brain glutamate (normalizing the glutamate\/glutamine ratio), glycine, serine and \u03b3-aminobutyric acid. Furthermore, ILB\u00ae administration restored arginine metabolism (preventing nitrosative stress), levels of amino acids involved in methylation reactions (methionine, L-cystathionine, S-adenosylhomocysteine), and N-acetylaspartate homeostasis. The macroscopic evidences of the beneficial effects on brain metabolism induced by ILB\u00ae were the relevant improvement in neurocognitive functions of the group of animals treated with ILB\u00ae 5 mg\/kg b.w., compared to the marked cognitive decline measured in untreated sTBI animals. These results demonstrate that ILB\u00ae administration 30 min after sTBI prevents glutamate excitotoxicity and normalizes levels of amino acids involved in crucial brain metabolic functions. The ameliorations of amino acid metabolism, mitochondrial functions and energy metabolism in ILB\u00ae-treated rats exposed to sTBI produced significant improvement in neurocognitive functions, reinforcing the concept that ILB\u00ae is a new effective therapeutic tool for the treatment of sTBI, worth being tested in the clinical setting.<\/jats:p>","DOI":"10.3390\/ijms23158460","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T02:06:42Z","timestamp":1659319602000},"page":"8460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["ILB\u00ae, a Low Molecular Weight Dextran Sulphate, Restores Glutamate Homeostasis, Amino Acid Metabolism and Neurocognitive Functions in a Rat Model of Severe Traumatic Brain Injury"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1639-0966","authenticated-orcid":false,"given":"Giacomo","family":"Lazzarino","sequence":"first","affiliation":[{"name":"Departmental Faculty of Medicine and Surgery, UniCamillus\u2014Saint Camillus International University of Health and Medical Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9430-4723","authenticated-orcid":false,"given":"Valentina","family":"Di Pietro","sequence":"additional","affiliation":[{"name":"Neurotrauma and Ophthalmology Research Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"National Institute for Health Research, Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6130-7335","authenticated-orcid":false,"given":"Marco","family":"Rinaudo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Catholic University of the Sacred Heart of Rome, Largo F. Vito 1, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6700-4829","authenticated-orcid":false,"given":"Zsuzsanna","family":"Nagy","sequence":"additional","affiliation":[{"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":"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":"Stefano","family":"Signoretti","sequence":"additional","affiliation":[{"name":"Departmental Faculty of Medicine and Surgery, UniCamillus\u2014Saint Camillus International University of Health and Medical Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"},{"name":"Division of Neurosurgery, Department of Emergency and Urgency, S. Eugenio\/CTO Hospital, A.S.L. Roma 2, Piazzale dell\u2019Umanesimo 10, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Mangione","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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam Wissam","family":"Saab","sequence":"additional","affiliation":[{"name":"Division of Medical Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-0895","authenticated-orcid":false,"given":"Barbara","family":"Tavazzi","sequence":"additional","affiliation":[{"name":"Departmental Faculty of Medicine and Surgery, UniCamillus\u2014Saint Camillus International University of Health and Medical Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Belli","sequence":"additional","affiliation":[{"name":"Neurotrauma and Ophthalmology Research Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"National Institute for Health Research, Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5917-7279","authenticated-orcid":false,"given":"Giuseppe","family":"Lazzarino","sequence":"additional","affiliation":[{"name":"Division of Medical Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, 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":"Division of Medical Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3215-5042","authenticated-orcid":false,"given":"Ann","family":"Logan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Warwick, Coventry CV4 7HL, UK"},{"name":"Axolotl Consulting Ltd., Droitwich WR9 0JS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,30]]},"reference":[{"key":"ref_1","unstructured":"Center for Disease Control and Prevention (2022, April 14). 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