OXIDATIVE AND NITROSATIVE DISTURBANCES IN THE RAT BRAIN FOLLOWING REPEATED MILD TRAUMATIC BRAIN INJURY

The aim of this study was to determine the patterns of oxidative and nitrosative stress development in cerebral hemisphere homogenates of rats exposed to repeated mild traumatic brain injury (rmTBI). Materials and methods. The study was conducted on 28 male rats, divided into three groups: Group 1 (...

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Main Authors: I.M. Adamovych, V.O. Kostenko
Format: Article
Language:English
Published: Poltava State Medical University 2025-04-01
Series:Проблеми екології та медицини
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Online Access:https://ecomed-journal.org/index.php/journal/article/view/317
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author I.M. Adamovych
V.O. Kostenko
author_facet I.M. Adamovych
V.O. Kostenko
author_sort I.M. Adamovych
collection DOAJ
description The aim of this study was to determine the patterns of oxidative and nitrosative stress development in cerebral hemisphere homogenates of rats exposed to repeated mild traumatic brain injury (rmTBI). Materials and methods. The study was conducted on 28 male rats, divided into three groups: Group 1 (control) – intact animals; Group 2 – sham-injured rats, which underwent anesthesia and head fixation without trauma (five procedures at 48-hour intervals); and Group 3 – rats subjected to repeated mild traumatic brain injury (rmTBI), involving anesthesia, fixation, and impact-induced injury (five procedures at 48-hour intervals). rmTBI was modeled by applying an impact with a 49.5 g weight to the skull of rats under under inhalation anesthesia with sevoflurane. Spectrophotometric methods were used to evaluate the rate of superoxide anion radical production, the activity of various nitric oxide synthase (NOS) isoforms, and the levels of reactive nitrogen species, including nitrite ions, S-nitrosothiols, and 3-nitrotyrosine. Results. The study revealed that even sham injury led to a moderate increase in superoxide anion radical production: by microsomes (+9.2%), by mitochondria (+19.6%), by leukocytes and glial cells (+42.6%). Endothelial NOS activity increased by 44%, S-nitrosothiol concentration decreased by 27.9%, and 3-nitrotyrosine content rose by 110.6%. Following rmTBI, a significant increase in superoxide production was observed relative to the sham-injured group: by microsomes (+16.2%), by mitochondria (+11.7%), by leukocytes and glial cells (+ 42.9%). In the sham-injured group, total NOS activity increased by 45.6%, mainly due to inducible NOS (+93.8%) and neuronal NOS (+27.8%), the levels of nitrites, S-nitrosothiols, and 3-nitrotyrosine rose by 72.5%, 47.7%, and 57.6%, respectively, indicating the development of pronounced oxidative and nitrosative stress and potential protein nitration in brain tissue after rmTBI. Conclusions. By day 14 following rmTBI, pronounced signs of oxidative and nitrosative stress were evident in the cerebral hemispheres of rats. Sham injury also led to moderate changes in oxidative imbalance markers. These findings highlight the potential of redox biomarkers as promising targets for neuroprotective interventions in the aftermath of rmTBI.
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spelling doaj-art-8a66b6740deb45a08e92ee2ddda4905f2025-08-20T02:29:04ZengPoltava State Medical UniversityПроблеми екології та медицини2073-46622519-23022025-04-0129151210.31718/mep.2025.29.1.01317OXIDATIVE AND NITROSATIVE DISTURBANCES IN THE RAT BRAIN FOLLOWING REPEATED MILD TRAUMATIC BRAIN INJURYI.M. Adamovych0V.O. Kostenko1Poltava State Medical University, Poltava, UkrainePoltava State Medical University, Poltava, UkraineThe aim of this study was to determine the patterns of oxidative and nitrosative stress development in cerebral hemisphere homogenates of rats exposed to repeated mild traumatic brain injury (rmTBI). Materials and methods. The study was conducted on 28 male rats, divided into three groups: Group 1 (control) – intact animals; Group 2 – sham-injured rats, which underwent anesthesia and head fixation without trauma (five procedures at 48-hour intervals); and Group 3 – rats subjected to repeated mild traumatic brain injury (rmTBI), involving anesthesia, fixation, and impact-induced injury (five procedures at 48-hour intervals). rmTBI was modeled by applying an impact with a 49.5 g weight to the skull of rats under under inhalation anesthesia with sevoflurane. Spectrophotometric methods were used to evaluate the rate of superoxide anion radical production, the activity of various nitric oxide synthase (NOS) isoforms, and the levels of reactive nitrogen species, including nitrite ions, S-nitrosothiols, and 3-nitrotyrosine. Results. The study revealed that even sham injury led to a moderate increase in superoxide anion radical production: by microsomes (+9.2%), by mitochondria (+19.6%), by leukocytes and glial cells (+42.6%). Endothelial NOS activity increased by 44%, S-nitrosothiol concentration decreased by 27.9%, and 3-nitrotyrosine content rose by 110.6%. Following rmTBI, a significant increase in superoxide production was observed relative to the sham-injured group: by microsomes (+16.2%), by mitochondria (+11.7%), by leukocytes and glial cells (+ 42.9%). In the sham-injured group, total NOS activity increased by 45.6%, mainly due to inducible NOS (+93.8%) and neuronal NOS (+27.8%), the levels of nitrites, S-nitrosothiols, and 3-nitrotyrosine rose by 72.5%, 47.7%, and 57.6%, respectively, indicating the development of pronounced oxidative and nitrosative stress and potential protein nitration in brain tissue after rmTBI. Conclusions. By day 14 following rmTBI, pronounced signs of oxidative and nitrosative stress were evident in the cerebral hemispheres of rats. Sham injury also led to moderate changes in oxidative imbalance markers. These findings highlight the potential of redox biomarkers as promising targets for neuroprotective interventions in the aftermath of rmTBI.https://ecomed-journal.org/index.php/journal/article/view/317traumatic brain injuryoxidative and nitrosative stressreactive oxygen and nitrogen speciessuperoxide anion radicalnitric oxide synthase3-nitrotyrosines-nitrosothiolsneuroinflammationbrainrats
spellingShingle I.M. Adamovych
V.O. Kostenko
OXIDATIVE AND NITROSATIVE DISTURBANCES IN THE RAT BRAIN FOLLOWING REPEATED MILD TRAUMATIC BRAIN INJURY
Проблеми екології та медицини
traumatic brain injury
oxidative and nitrosative stress
reactive oxygen and nitrogen species
superoxide anion radical
nitric oxide synthase
3-nitrotyrosine
s-nitrosothiols
neuroinflammation
brain
rats
title OXIDATIVE AND NITROSATIVE DISTURBANCES IN THE RAT BRAIN FOLLOWING REPEATED MILD TRAUMATIC BRAIN INJURY
title_full OXIDATIVE AND NITROSATIVE DISTURBANCES IN THE RAT BRAIN FOLLOWING REPEATED MILD TRAUMATIC BRAIN INJURY
title_fullStr OXIDATIVE AND NITROSATIVE DISTURBANCES IN THE RAT BRAIN FOLLOWING REPEATED MILD TRAUMATIC BRAIN INJURY
title_full_unstemmed OXIDATIVE AND NITROSATIVE DISTURBANCES IN THE RAT BRAIN FOLLOWING REPEATED MILD TRAUMATIC BRAIN INJURY
title_short OXIDATIVE AND NITROSATIVE DISTURBANCES IN THE RAT BRAIN FOLLOWING REPEATED MILD TRAUMATIC BRAIN INJURY
title_sort oxidative and nitrosative disturbances in the rat brain following repeated mild traumatic brain injury
topic traumatic brain injury
oxidative and nitrosative stress
reactive oxygen and nitrogen species
superoxide anion radical
nitric oxide synthase
3-nitrotyrosine
s-nitrosothiols
neuroinflammation
brain
rats
url https://ecomed-journal.org/index.php/journal/article/view/317
work_keys_str_mv AT imadamovych oxidativeandnitrosativedisturbancesintheratbrainfollowingrepeatedmildtraumaticbraininjury
AT vokostenko oxidativeandnitrosativedisturbancesintheratbrainfollowingrepeatedmildtraumaticbraininjury