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

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 s...

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Autores principales: Lazzarino, Giacomo, Amorini, Angela Maria, Barnes, Nicholas M., Bruce, Lars, Mordente, Alvaro, Lazzarino, Giuseppe, Pietro, Valentina Di, Tavazzi, Barbara, Belli, Antonio, Logan, Ann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555574/
https://www.ncbi.nlm.nih.gov/pubmed/32927770
http://dx.doi.org/10.3390/antiox9090850
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author Lazzarino, Giacomo
Amorini, Angela Maria
Barnes, Nicholas M.
Bruce, Lars
Mordente, Alvaro
Lazzarino, Giuseppe
Pietro, Valentina Di
Tavazzi, Barbara
Belli, Antonio
Logan, Ann
author_facet Lazzarino, Giacomo
Amorini, Angela Maria
Barnes, Nicholas M.
Bruce, Lars
Mordente, Alvaro
Lazzarino, Giuseppe
Pietro, Valentina Di
Tavazzi, Barbara
Belli, Antonio
Logan, Ann
author_sort Lazzarino, Giacomo
collection PubMed
description 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.
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spelling pubmed-75555742020-10-19 Low Molecular Weight Dextran Sulfate (ILB(®)) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat Lazzarino, Giacomo Amorini, Angela Maria Barnes, Nicholas M. Bruce, Lars Mordente, Alvaro Lazzarino, Giuseppe Pietro, Valentina Di Tavazzi, Barbara Belli, Antonio Logan, Ann Antioxidants (Basel) Article 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. MDPI 2020-09-10 /pmc/articles/PMC7555574/ /pubmed/32927770 http://dx.doi.org/10.3390/antiox9090850 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lazzarino, Giacomo
Amorini, Angela Maria
Barnes, Nicholas M.
Bruce, Lars
Mordente, Alvaro
Lazzarino, Giuseppe
Pietro, Valentina Di
Tavazzi, Barbara
Belli, Antonio
Logan, Ann
Low Molecular Weight Dextran Sulfate (ILB(®)) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat
title Low Molecular Weight Dextran Sulfate (ILB(®)) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat
title_full Low Molecular Weight Dextran Sulfate (ILB(®)) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat
title_fullStr Low Molecular Weight Dextran Sulfate (ILB(®)) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat
title_full_unstemmed Low Molecular Weight Dextran Sulfate (ILB(®)) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat
title_short Low Molecular Weight Dextran Sulfate (ILB(®)) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat
title_sort low molecular weight dextran sulfate (ilb(®)) administration restores brain energy metabolism following severe traumatic brain injury in the rat
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555574/
https://www.ncbi.nlm.nih.gov/pubmed/32927770
http://dx.doi.org/10.3390/antiox9090850
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