Subchronic Intranasal Administration of NeuroEPO Reduces Long-Term Consequences of Severe Traumatic Brain Injury in Male Rats

Current treatments fail to prevent long-term consequences induced by a severe traumatic brain injury (TBI). This study aimed to evaluate the efficacy of repetitive intranasal administration of NeuroEPO (a derivative of erythropoietin) on long-term alterations after a severe TBI induced by the applic...

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Main Authors: Félix Iván López-Preza, Maria de los Angeles Nuñez-Lumbreras, Iliana Sosa-Testé, Alonso Fernández-Guasti, Luis Concha, Teresita Rodríguez-Obaya, Luisa Rocha
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/14/6/710
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author Félix Iván López-Preza
Maria de los Angeles Nuñez-Lumbreras
Iliana Sosa-Testé
Alonso Fernández-Guasti
Luis Concha
Teresita Rodríguez-Obaya
Luisa Rocha
author_facet Félix Iván López-Preza
Maria de los Angeles Nuñez-Lumbreras
Iliana Sosa-Testé
Alonso Fernández-Guasti
Luis Concha
Teresita Rodríguez-Obaya
Luisa Rocha
author_sort Félix Iván López-Preza
collection DOAJ
description Current treatments fail to prevent long-term consequences induced by a severe traumatic brain injury (TBI). This study aimed to evaluate the efficacy of repetitive intranasal administration of NeuroEPO (a derivative of erythropoietin) on long-term alterations after a severe TBI induced by the application of a lateral fluid percussion in male rats. A otal of 30–31 days after the trauma, TBI+vehicle group showed sensorimotor dysfunction (Neuroscore, <i>p</i> < 0.0009; beam walking test, <i>p</i> < 0.0001 vs. Sham+vehicle group) and depressive-like behavior suggested by increased immobility (<i>p</i> = 0.0009 vs. baseline) during the forced swim test. Rats also showed increased production of malondialdehyde (a marker of oxidative damage), increased catalase activity (an antioxidant enzyme), and atrophy of brain areas evaluated with Magnetic Resonance Imaging 31 days after the trauma. TBI+NeuroEPO group received intranasal administration of NeuroEPO (0.136 mg/kg) starting 3 h post-TBI and continued every 8 h for four days. This group showed less sensorimotor dysfunction (Neuroscore, <i>p</i> = 0.020; beam walking test, <i>p</i> = 0.001, vs. TBI+vehicle group) and normal immobility behavior (<i>p</i> = 0.998 vs. Sham+vehicle group). Levels of malondialdehyde and catalase as well as the volume of brain structures of this group were like the Sham+vehicle group. These findings support the potential of NeuroEPO as a therapeutic agent to reduce long-term consequences of TBI.
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spelling doaj-art-65939863e2154b05be86c99e1ab7f58d2025-08-20T03:32:26ZengMDPI AGAntioxidants2076-39212025-06-0114671010.3390/antiox14060710Subchronic Intranasal Administration of NeuroEPO Reduces Long-Term Consequences of Severe Traumatic Brain Injury in Male RatsFélix Iván López-Preza0Maria de los Angeles Nuñez-Lumbreras1Iliana Sosa-Testé2Alonso Fernández-Guasti3Luis Concha4Teresita Rodríguez-Obaya5Luisa Rocha6Pharmacobiology Department, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Mexico City C.P. 14330, MexicoPharmacobiology Department, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Mexico City C.P. 14330, MexicoCenter for the Production of Laboratory Animals (CENPALAB), Havana C.P. 10300, CubaPharmacobiology Department, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Mexico City C.P. 14330, MexicoInstitute of Neurobiology, National Autonomous University of Mexico, Campus Juriquilla, Juriquilla C.P. 76230, Queretaro, MexicoCenter for Molecular Immunology (CIM), Havana C.P. 11600, CubaPharmacobiology Department, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Mexico City C.P. 14330, MexicoCurrent treatments fail to prevent long-term consequences induced by a severe traumatic brain injury (TBI). This study aimed to evaluate the efficacy of repetitive intranasal administration of NeuroEPO (a derivative of erythropoietin) on long-term alterations after a severe TBI induced by the application of a lateral fluid percussion in male rats. A otal of 30–31 days after the trauma, TBI+vehicle group showed sensorimotor dysfunction (Neuroscore, <i>p</i> < 0.0009; beam walking test, <i>p</i> < 0.0001 vs. Sham+vehicle group) and depressive-like behavior suggested by increased immobility (<i>p</i> = 0.0009 vs. baseline) during the forced swim test. Rats also showed increased production of malondialdehyde (a marker of oxidative damage), increased catalase activity (an antioxidant enzyme), and atrophy of brain areas evaluated with Magnetic Resonance Imaging 31 days after the trauma. TBI+NeuroEPO group received intranasal administration of NeuroEPO (0.136 mg/kg) starting 3 h post-TBI and continued every 8 h for four days. This group showed less sensorimotor dysfunction (Neuroscore, <i>p</i> = 0.020; beam walking test, <i>p</i> = 0.001, vs. TBI+vehicle group) and normal immobility behavior (<i>p</i> = 0.998 vs. Sham+vehicle group). Levels of malondialdehyde and catalase as well as the volume of brain structures of this group were like the Sham+vehicle group. These findings support the potential of NeuroEPO as a therapeutic agent to reduce long-term consequences of TBI.https://www.mdpi.com/2076-3921/14/6/710traumatic brain injuryNeuroEPOsensorimotor functionoxidative stressdepression-like behaviormagnetic resonance imaging
spellingShingle Félix Iván López-Preza
Maria de los Angeles Nuñez-Lumbreras
Iliana Sosa-Testé
Alonso Fernández-Guasti
Luis Concha
Teresita Rodríguez-Obaya
Luisa Rocha
Subchronic Intranasal Administration of NeuroEPO Reduces Long-Term Consequences of Severe Traumatic Brain Injury in Male Rats
Antioxidants
traumatic brain injury
NeuroEPO
sensorimotor function
oxidative stress
depression-like behavior
magnetic resonance imaging
title Subchronic Intranasal Administration of NeuroEPO Reduces Long-Term Consequences of Severe Traumatic Brain Injury in Male Rats
title_full Subchronic Intranasal Administration of NeuroEPO Reduces Long-Term Consequences of Severe Traumatic Brain Injury in Male Rats
title_fullStr Subchronic Intranasal Administration of NeuroEPO Reduces Long-Term Consequences of Severe Traumatic Brain Injury in Male Rats
title_full_unstemmed Subchronic Intranasal Administration of NeuroEPO Reduces Long-Term Consequences of Severe Traumatic Brain Injury in Male Rats
title_short Subchronic Intranasal Administration of NeuroEPO Reduces Long-Term Consequences of Severe Traumatic Brain Injury in Male Rats
title_sort subchronic intranasal administration of neuroepo reduces long term consequences of severe traumatic brain injury in male rats
topic traumatic brain injury
NeuroEPO
sensorimotor function
oxidative stress
depression-like behavior
magnetic resonance imaging
url https://www.mdpi.com/2076-3921/14/6/710
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