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Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury

Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality in adults under 40 years old. Once primary injury occurs after TBI, neuroinflammation and oxidative stress (OS) are triggered, contributing to the development of many TBI-induced neurological deficits, and reducing the p...

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Autores principales: Montivero, Agustín. J., Ghersi, Marisa. S., Silvero C, M. Jazmín, Artur de la Villarmois, Emilce, Catalan-Figueroa, Johanna, Herrera, Macarena, Becerra, María Cecilia, Hereñú, Claudia. B., Pérez, Mariela. F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255687/
https://www.ncbi.nlm.nih.gov/pubmed/34234671
http://dx.doi.org/10.3389/fphar.2021.672392
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author Montivero, Agustín. J.
Ghersi, Marisa. S.
Silvero C, M. Jazmín
Artur de la Villarmois, Emilce
Catalan-Figueroa, Johanna
Herrera, Macarena
Becerra, María Cecilia
Hereñú, Claudia. B.
Pérez, Mariela. F.
author_facet Montivero, Agustín. J.
Ghersi, Marisa. S.
Silvero C, M. Jazmín
Artur de la Villarmois, Emilce
Catalan-Figueroa, Johanna
Herrera, Macarena
Becerra, María Cecilia
Hereñú, Claudia. B.
Pérez, Mariela. F.
author_sort Montivero, Agustín. J.
collection PubMed
description Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality in adults under 40 years old. Once primary injury occurs after TBI, neuroinflammation and oxidative stress (OS) are triggered, contributing to the development of many TBI-induced neurological deficits, and reducing the probability of critical trauma patients´ survival. Regardless the research investment on the development of anti-inflammatory and neuroprotective treatments, most pre-clinical studies have failed to report significant effects, probably because of the limited blood brain barrier permeability of no-steroidal or steroidal anti-inflammatory drugs. Lately, neurotrophic factors, such as the insulin-like growth factor 1 (IGF-1), are considered attractive therapeutic alternatives for diverse neurological pathologies, as they are neuromodulators linked to neuroprotection and anti-inflammatory effects. Considering this background, the aim of the present investigation is to test early IGF-1 gene therapy in both OS markers and cognitive deficits induced by TBI. Male Wistar rats were injected via Cisterna Magna with recombinant adenoviral vectors containing the IGF-1 gene cDNA 15 min post-TBI. Animals were sacrificed after 60 min, 24 h or 7 days to study the advanced oxidation protein products (AOPP) and malondialdehyde (MDA) levels, to recognize the protein oxidation damage and lipid peroxidation respectively, in the TBI neighboring brain areas. Cognitive deficits were assessed by evaluating working memory 7 days after TBI. The results reported significant increases of AOPP and MDA levels at 60 min, 24 h, and 7 days after TBI in the prefrontal cortex, motor cortex and hippocampus. In addition, at day 7, TBI also reduced working memory performance. Interestingly, AOPP, and MDA levels in the studied brain areas were significantly reduced after IGF-1 gene therapy that in turn prevented cognitive deficits, restoring TBI-animals working memory performance to similar values regarding control. In conclusion, early IGF-1 gene therapy could be considered a novel therapeutic approach to targeting neuroinflammation as well as to preventing some behavioral deficits related to TBI.
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spelling pubmed-82556872021-07-06 Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury Montivero, Agustín. J. Ghersi, Marisa. S. Silvero C, M. Jazmín Artur de la Villarmois, Emilce Catalan-Figueroa, Johanna Herrera, Macarena Becerra, María Cecilia Hereñú, Claudia. B. Pérez, Mariela. F. Front Pharmacol Pharmacology Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality in adults under 40 years old. Once primary injury occurs after TBI, neuroinflammation and oxidative stress (OS) are triggered, contributing to the development of many TBI-induced neurological deficits, and reducing the probability of critical trauma patients´ survival. Regardless the research investment on the development of anti-inflammatory and neuroprotective treatments, most pre-clinical studies have failed to report significant effects, probably because of the limited blood brain barrier permeability of no-steroidal or steroidal anti-inflammatory drugs. Lately, neurotrophic factors, such as the insulin-like growth factor 1 (IGF-1), are considered attractive therapeutic alternatives for diverse neurological pathologies, as they are neuromodulators linked to neuroprotection and anti-inflammatory effects. Considering this background, the aim of the present investigation is to test early IGF-1 gene therapy in both OS markers and cognitive deficits induced by TBI. Male Wistar rats were injected via Cisterna Magna with recombinant adenoviral vectors containing the IGF-1 gene cDNA 15 min post-TBI. Animals were sacrificed after 60 min, 24 h or 7 days to study the advanced oxidation protein products (AOPP) and malondialdehyde (MDA) levels, to recognize the protein oxidation damage and lipid peroxidation respectively, in the TBI neighboring brain areas. Cognitive deficits were assessed by evaluating working memory 7 days after TBI. The results reported significant increases of AOPP and MDA levels at 60 min, 24 h, and 7 days after TBI in the prefrontal cortex, motor cortex and hippocampus. In addition, at day 7, TBI also reduced working memory performance. Interestingly, AOPP, and MDA levels in the studied brain areas were significantly reduced after IGF-1 gene therapy that in turn prevented cognitive deficits, restoring TBI-animals working memory performance to similar values regarding control. In conclusion, early IGF-1 gene therapy could be considered a novel therapeutic approach to targeting neuroinflammation as well as to preventing some behavioral deficits related to TBI. Frontiers Media S.A. 2021-06-21 /pmc/articles/PMC8255687/ /pubmed/34234671 http://dx.doi.org/10.3389/fphar.2021.672392 Text en Copyright © 2021 Montivero, Ghersi, Silvero C, Artur de la Villarmois, Catalan-Figueroa, Herrera, Becerra, Hereñú and Pérez. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Montivero, Agustín. J.
Ghersi, Marisa. S.
Silvero C, M. Jazmín
Artur de la Villarmois, Emilce
Catalan-Figueroa, Johanna
Herrera, Macarena
Becerra, María Cecilia
Hereñú, Claudia. B.
Pérez, Mariela. F.
Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury
title Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury
title_full Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury
title_fullStr Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury
title_full_unstemmed Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury
title_short Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury
title_sort early igf-1 gene therapy prevented oxidative stress and cognitive deficits induced by traumatic brain injury
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255687/
https://www.ncbi.nlm.nih.gov/pubmed/34234671
http://dx.doi.org/10.3389/fphar.2021.672392
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