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Oxidative Stress and Brain Injury

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (22 December 2019) | Viewed by 42160

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Prof. Dr. Vittorio Fineschi

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Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, RM, Italy
Interests: forensic pathology; sudden cardiac death; molecular mechanisms; traumatic brain injury & oxidative stress; immunohistochemistry; drugs of abuse; oxidative stress; maternal mortality; miRNA; forensic pathologies
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Prof. Dr. Andreas Buettner

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Director and Chair, Institute of Forensic Medicine/Rechtsmedizin, Rostock University Medical Center, Rostock, Germany
Interests: forensic neuropathology, traumatic brain injury, drugs of abuse, forensic histopathology

Special Issue Information

Dear Colleagues,

Scientific literature gave extensive prominence about the effects of reactive oxygen species (ROS) induced oxidative stress and its fatal effects on brain after injury by endogenous factors, traumatic brain injury, and degenerative neural injury eventually due to ROS. Oxidative stress is an event caused by an imbalance between biochemical processes leading to the production of ROS and those responsible for the removal of ROS, known as the enzymatic and non-enzymatic antioxidant cellular defense systems. The excessive production of ROS due to excitotoxicity and depletion of the endogenous antioxidant system induces peroxidation of cellular and vascular structures, protein oxidation, and inhibition of the mitochondrial electron transport chain, causing oxidative cellular damage. Oxidative stress induces cell membrane lipoperoxidation and calcium release, which activates calpain. ROS and RNS induced oxidative damage in neuronal mitochondria and compromise Ca²⁺ homeostasis. Increase in the defense mechanisms through the use of exogenous antioxidants may be neuroprotective, particularly if they are given within the neuroprotective time window. As example, a promising potential therapeutic target in DAI is to directly address mitochondria related injury or to modulate energetic axonal energy failure. However, dietary supplementation with antioxidant and the use of pharmacological agents targeting oxidative stress seem logical but the benefits of proven antioxidant strategies have not been clearly demonstrated to date.

In this Special Issue on “Oxidative Stress and Brain Injury”, we invite front-line researchers and investigators to submit both original research and review articles regarding the following potential topics, but not limited to:

Measurement of ROS;
Pathology of brain injuries;
Traumatic brain injuries;
Hypoxic-ischemic brain damage;
Experimental Model of brain injuries;
Targeted therapy of brain injuries;
Drug of abuse and ROS;
Histological diagnosis of brain injuries;
Epigenetic of brain injuries;
miRNA and prognosis of neural damages;
Novel approach and proof of principle in therapy;
Related quality of life after brain injuries.

Prof. Dr. Vittorio Fineschi
Prof. Dr. Andreas Buettner
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

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Research

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14 pages, 2391 KiB

Open AccessArticle

Cannabinoid-mediated Modulation of Oxidative Stress and Early Inflammatory Response after Hypoxia–Ischemia

by Daniel Alonso-Alconada, Francisco José Álvarez, Felipe Goñi-de-Cerio, Enrique Hilario and Antonia Álvarez

Int. J. Mol. Sci. 2020, 21(4), 1283; https://doi.org/10.3390/ijms21041283 - 14 Feb 2020

Cited by 8 | Viewed by 2658

Abstract

In the process of neonatal encephalopathy, oxidative stress and neuroinflammation have a prominent role after perinatal asphyxia. With the exception of therapeutic hypothermia, no therapeutic interventions are available in the clinical setting to target either the oxidative stress or inflammation, despite the high prevalence of neurological sequelae of this devastating condition. The endocannabinoid system (ECS), recently recognized as a widespread neuromodulatory system, plays an important role in the development of the central nervous system (CNS). This study aims to evaluate the potential effect of the cannabinoid (CB) agonist WIN 55,212-2 (WIN) on reactive oxygen species (ROS) and early inflammatory cytokine production after hypoxia–ischemia (HI) in fetal lambs. Hypoxic–ischemic animals were subjected to 60 min of HI by partial occlusion of the umbilical cord. A group of lambs received a single dose of 0.01 μg/kg WIN, whereas non-asphyctic animals served as controls. WIN reduced the widespread and notorious increase in inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-6 induced by HI, a modulatory effect not observed for oxidative stress. Our study suggests that treatment with a low dose of WIN can alter the profile of pro-inflammatory cytokines 3 h after HI. Full article

(This article belongs to the Special Issue Oxidative Stress and Brain Injury)

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20 pages, 4384 KiB

Open AccessArticle

Mitochondrial Bioenergetics in Brain Following Ozone Exposure in Rats Maintained on Coconut, Fish and Olive Oil-Rich Diets

by Matthew C. Valdez, Danielle Freeborn, Joseph M. Valdez, Andrew F.M. Johnstone, Samantha J. Snow, Alan H. Tennant, Urmila P. Kodavanti and Prasada Rao S. Kodavanti

Int. J. Mol. Sci. 2019, 20(24), 6303; https://doi.org/10.3390/ijms20246303 - 13 Dec 2019

Cited by 14 | Viewed by 3240

Abstract

Dietary supplementation with omega-3 and omega-6 fatty acids offer cardioprotection against air pollution, but these protections have not been established in the brain. We tested whether diets rich in omega-3 or -6 fatty acids offered neuroprotective benefits, by measuring mitochondrial complex enzyme I, II and IV activities and oxidative stress measures in the frontal cortex, cerebellum, hypothalamus, and hippocampus of male rats that were fed either a normal diet, or a diet enriched with fish oil olive oil, or coconut oil followed by exposure to either filtered air or ozone (0.8 ppm) for 4 h/day for 2 days. Results show that mitochondrial complex I enzyme activity was significantly decreased in the cerebellum, hypothalamus and hippocampus by diets. Complex II enzyme activity was significantly lower in frontal cortex and cerebellum of rats maintained on all test diets. Complex IV enzyme activity was significantly lower in the frontal cortex, hypothalamus and hippocampus of animals maintained on fish oil. Ozone exposure decreased complex I and II activity in the cerebellum of rats maintained on the normal diet, an effect blocked by diet treatments. While diet and ozone have no apparent influence on endogenous reactive oxygen species production, they do affect antioxidant levels in the brain. Fish oil was the only diet that ozone exposure did not alter. Microglial morphology and GFAP immunoreactivity were assessed across diet groups; results indicated that fish oil consistently decreased reactive microglia in the hypothalamus and hippocampus. These results indicate that acute ozone exposure alters mitochondrial bioenergetics in brain and co-treatment with omega-6 and omega-3 fatty acids alleviate some adverse effects within the brain. Full article

(This article belongs to the Special Issue Oxidative Stress and Brain Injury)

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16 pages, 2391 KiB

Open AccessArticle

High Protein Diet Induces Oxidative Stress in Rat Cerebral Cortex and Hypothalamus

by Ewa Żebrowska, Mateusz Maciejczyk, Małgorzata Żendzian-Piotrowska, Anna Zalewska and Adrian Chabowski

Int. J. Mol. Sci. 2019, 20(7), 1547; https://doi.org/10.3390/ijms20071547 - 28 Mar 2019

Cited by 33 | Viewed by 4214

Abstract

This is the first study to analyze the impact of high protein diet (HPD) on antioxidant defense, redox status, as well as oxidative damage on both a local and systemic level. Male Wistar rats were divided into two equal groups (n = 9): HPD (44% protein) and standard diet (CON; 24.2% protein). After eight weeks, glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase-1 (SOD-1), reduced glutathione (GSH), uric acid (UA), total antioxidant (TAC)/oxidant status (TOS) as well as advanced glycation end products (AGE), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were analyzed in the serum/plasma, cerebral cortex, and hypothalamus of HPD and CON rats. HPD resulted in higher UA concentration and activity of GPx and CAT in the hypothalamus, whereas in the cerebral cortex these parameters remained unchanged. A significantly lower GSH content was demonstrated in the plasma and hypothalamus of HPD rats when compared to CON rats. Both brain structures expressed higher content of 4-HNE and MDA, whereas AGE was increased only in the hypothalamus of HPD animals. Despite the enhancement in antioxidant defense in the hypothalamus, this mechanism does not protect the hypothalamus from oxidative damage in rats. Hypothalamus is more susceptible to oxidative stress caused by HPD. Full article

(This article belongs to the Special Issue Oxidative Stress and Brain Injury)

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13 pages, 1278 KiB

Open AccessCommunication

Human Brain Injury and miRNAs: An Experimental Study

by Francesco Sessa, Francesca Maglietta, Giuseppe Bertozzi, Monica Salerno, Giulio Di Mizio, Giovanni Messina, Angelo Montana, Pietrantonio Ricci and Cristoforo Pomara

Int. J. Mol. Sci. 2019, 20(7), 1546; https://doi.org/10.3390/ijms20071546 - 27 Mar 2019

Cited by 42 | Viewed by 3961

Abstract

Brain damage is a complex dysfunction that involves a variety of conditions whose pathogenesis involves a number of mediators that lead to clinical sequelae. For this reason, the identification of specific circulating and/or tissue biomarkers which could indicate brain injury is challenging. This experimental study focused on microRNAs (miRNAs), a well-known diagnostic tool both in the clinical setting and in medico-legal investigation. Previous studies demonstrated that specific miRNAs (miR-21, miR-34, miR-124, miR-132, and miR-200b) control important target genes involved in neuronal apoptosis and neuronal stress-induced adaptation. Thus, in this experimental setting, their expression was evaluated in three selected groups of cadavers: drug abusers (cocaine), ischemic-stroke-related deaths, and aging damage in elder people who died from other neurological causes. The results demonstrated that the drug abuser group showed a higher expression of miR-132 and miR-34, suggesting a specific pathway in consumption-induced neurodegeneration. Instead, miR-200b and miR-21 dysregulation was linked to age-related cognitive impairment, and finally, stroke events and consequences were associated with an alteration in miR-200b, miR-21, and miR-124; significantly higher levels of this last expression are strongly sensitive for ischemic damage. Moreover, these results suggest that these expression patterns could be studied in other biological samples (plasma, urine) in subjects with brain injury linked to aging, drug abuse, and stroke to identify reliable biomarkers that could be applied in clinical practice. Further studies with larger samples are needed to confirm these interesting findings. Full article

(This article belongs to the Special Issue Oxidative Stress and Brain Injury)

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20 pages, 4504 KiB

Open AccessArticle

Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats

by Stefania Schiavone, Margherita Neri, Angela Bruna Maffione, Paolo Frisoni, Maria Grazia Morgese, Luigia Trabace and Emanuela Turillazzi

Int. J. Mol. Sci. 2019, 20(5), 1242; https://doi.org/10.3390/ijms20051242 - 12 Mar 2019

Cited by 15 | Viewed by 4711

Abstract

Several mechanisms underlying 3,4-Methylenedioxy-N-methylamphetamine (MDMA) neurotoxicity have been proposed, including neurochemical alterations and excitotoxicity mediated by reactive oxygen species (ROS), nitric oxide (NO), and reactive nitrogen species (RNS). However, ROS, NO, and RNS sources in the brain are not fully known. We aimed to investigate possible alterations in the expression of the ROS producer NOX enzymes (NOX2, NOX1, and NOX4), NO generators (iNOS, eNOS, and nNOS), markers of oxidative (8-hydroxy-2′-deoxyguanosine, 8OHdG), and nitrosative (3-nitrotyrosine, NT) stress, as well as the colocalization between cells positive for the dopamine transporter (DT1) and cells expressing the neuronal nuclei (NeuN) marker, in the frontal cortex of rats receiving saline or MDMA, sacrificed 6 h, 16 h, or 24 h after its administration. MDMA did not affect NOX2, NOX1, and NOX4 immunoreactivity, whereas iNOS expression was enhanced. The number of NT-positive cells was increased in MDMA-exposed animals, whereas no differences were detected in 8OHdG expression among experimental groups. MDMA and NT markers colocalized with DT1 positive cells. DT1 immunostaining was found in NeuN-positive stained cells. Virtually no colocalization was observed with microglia and astrocytes. Moreover, MDMA immunostaining was not found in NOX2-positive cells. Our results suggest that iNOS-derived nitrosative stress, but not NOX enzymes, may have a crucial role in the pathogenesis of MDMA-induced neurotoxicity, highlighting the specificity of different enzymatic systems in the development of neuropathological alterations induced by the abuse of this psychoactive compound. Full article

(This article belongs to the Special Issue Oxidative Stress and Brain Injury)

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Review

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26 pages, 6792 KiB

Open AccessReview

Acute Spinal Cord Injury: A Systematic Review Investigating miRNA Families Involved

by Enrica Pinchi, Alessandro Frati, Santina Cantatore, Stefano D’Errico, Raffaele La Russa, Aniello Maiese, Mauro Palmieri, Alessandro Pesce, Rocco Valerio Viola, Paola Frati and Vittorio Fineschi

Int. J. Mol. Sci. 2019, 20(8), 1841; https://doi.org/10.3390/ijms20081841 - 13 Apr 2019

Cited by 54 | Viewed by 7968

Abstract

Acute traumatic spinal cord injury (SCI) involves primary and secondary injury mechanisms. The primary mechanism is related to the initial traumatic damage caused by the damaging impact and this damage is irreversible. Secondary mechanisms, which begin as early as a few minutes after the initial trauma, include processes such as spinal cord ischemia, cellular excitotoxicity, ionic dysregulation, and free radical-mediated peroxidation. SCI is featured by different forms of injury, investigating the pathology and degree of clinical diagnosis and treatment strategies, the animal models that have allowed us to better understand this entity and, finally, the role of new diagnostic and prognostic tools such as miRNA could improve our ability to manage this pathological entity. Autopsy could benefit from improvements in miRNA research: the specificity and sensitivity of miRNAs could help physicians in determining the cause of death, besides the time of death. Full article

(This article belongs to the Special Issue Oxidative Stress and Brain Injury)

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18 pages, 1584 KiB

Open AccessReview

Insulin Resistance and Oxidative Stress in the Brain: What’s New?

by Mateusz Maciejczyk, Ewa Żebrowska and Adrian Chabowski

Int. J. Mol. Sci. 2019, 20(4), 874; https://doi.org/10.3390/ijms20040874 - 18 Feb 2019

Cited by 146 | Viewed by 14127

Abstract

The latest studies have indicated a strong relationship between systemic insulin resistance (IR) and higher incidence of neurodegeneration, dementia, and mild cognitive impairment. Although some of these abnormalities could be explained by chronic hyperglycaemia, hyperinsulinemia, dyslipidaemia, and/or prolonged whole-body inflammation, the key role is attributed to the neuronal redox imbalance and oxidative damage. In this mini review, we provide a schematic overview of intracellular oxidative stress and mitochondrial abnormalities in the IR brain. We highlight important correlations found so far between brain oxidative stress, ceramide generation, β-amyloid accumulation, as well as neuronal apoptosis in the IR conditions. Full article

(This article belongs to the Special Issue Oxidative Stress and Brain Injury)

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