Antioxidant Bioactive Agents for Neuroprotection Against Perinatal Brain Injury

Physiological oxidative stress plays a pivotal role in supporting proper growth and development. While moderate oxidative stress is essential for activating key metabolic pathways and maintaining normal cellular signaling, excessive production of reactive oxygen species (ROSs) can overwhelm the imma...

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Main Authors: Virginia Beretta, Elena Scarpa, Silvia Carloni, Chiara Petrolini, Valentina Dell’Orto, Sebastiano Ravenda, Serafina Perrone
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/11/818
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author Virginia Beretta
Elena Scarpa
Silvia Carloni
Chiara Petrolini
Valentina Dell’Orto
Sebastiano Ravenda
Serafina Perrone
author_facet Virginia Beretta
Elena Scarpa
Silvia Carloni
Chiara Petrolini
Valentina Dell’Orto
Sebastiano Ravenda
Serafina Perrone
author_sort Virginia Beretta
collection DOAJ
description Physiological oxidative stress plays a pivotal role in supporting proper growth and development. While moderate oxidative stress is essential for activating key metabolic pathways and maintaining normal cellular signaling, excessive production of reactive oxygen species (ROSs) can overwhelm the immature antioxidant systems of newborns, potentially leading to cellular damage and impaired physiological function. This vulnerability is particularly pronounced in the central nervous system, where limited detoxification capacity exacerbates the risk of oxidative damage, following hypoxic–ischemic events. Antioxidants agents—such as melatonin, erythropoietin, allopurinol, N-acetylcisteine, selenium, iminobiotin, taurine, and acetyl-L-carnitine—have demonstrated significant neuroprotective effects in preclinical experimental studies, reducing markers of oxidative injury and improving neurological outcomes. These neuroprotective agents have also been evaluated in clinical trials, demonstrating antioxidant effects. A major issue lies in the complexity of neurological damage, which is not associated with a single pathological pathway. Additionally, the inability of these agents to reach effective concentrations within the central nervous system, along with inconsistencies across clinical trials in terms of dosage and administration methods, hinders the ability to obtain robust results. Future efforts should therefore focus on the development of delivery systems capable of crossing the blood–brain barrier and on establishing standardized clinical trial protocols and study designs. This educational review aims to provide a comprehensive overview of emerging protective strategies, including antioxidant bioactive agents and nutritional interventions. It also explores the underlying mechanisms of oxidative stress and its impact on neonatal brain injury.
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spelling doaj-art-6f9f06a626c84c6c92f0aaa5472eae152025-08-20T02:23:03ZengMDPI AGCells2073-44092025-05-01141181810.3390/cells14110818Antioxidant Bioactive Agents for Neuroprotection Against Perinatal Brain InjuryVirginia Beretta0Elena Scarpa1Silvia Carloni2Chiara Petrolini3Valentina Dell’Orto4Sebastiano Ravenda5Serafina Perrone6Neonatology Unit, Department of Medicine and Surgery, University of Parma, Pietro Barilla Children’s Hospital, 43121 Parma, ItalyNeonatology Unit, Department of Medicine and Surgery, University of Parma, Pietro Barilla Children’s Hospital, 43121 Parma, ItalyDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, ItalyNeonatology Unit, Department of Medicine and Surgery, University of Parma, Pietro Barilla Children’s Hospital, 43121 Parma, ItalyNeonatology Unit, Department of Medicine and Surgery, University of Parma, Pietro Barilla Children’s Hospital, 43121 Parma, ItalyStress Physiology Lab, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Viale delle Scienze 11, 43125 Parma, ItalyNeonatology Unit, Department of Medicine and Surgery, University of Parma, Pietro Barilla Children’s Hospital, 43121 Parma, ItalyPhysiological oxidative stress plays a pivotal role in supporting proper growth and development. While moderate oxidative stress is essential for activating key metabolic pathways and maintaining normal cellular signaling, excessive production of reactive oxygen species (ROSs) can overwhelm the immature antioxidant systems of newborns, potentially leading to cellular damage and impaired physiological function. This vulnerability is particularly pronounced in the central nervous system, where limited detoxification capacity exacerbates the risk of oxidative damage, following hypoxic–ischemic events. Antioxidants agents—such as melatonin, erythropoietin, allopurinol, N-acetylcisteine, selenium, iminobiotin, taurine, and acetyl-L-carnitine—have demonstrated significant neuroprotective effects in preclinical experimental studies, reducing markers of oxidative injury and improving neurological outcomes. These neuroprotective agents have also been evaluated in clinical trials, demonstrating antioxidant effects. A major issue lies in the complexity of neurological damage, which is not associated with a single pathological pathway. Additionally, the inability of these agents to reach effective concentrations within the central nervous system, along with inconsistencies across clinical trials in terms of dosage and administration methods, hinders the ability to obtain robust results. Future efforts should therefore focus on the development of delivery systems capable of crossing the blood–brain barrier and on establishing standardized clinical trial protocols and study designs. This educational review aims to provide a comprehensive overview of emerging protective strategies, including antioxidant bioactive agents and nutritional interventions. It also explores the underlying mechanisms of oxidative stress and its impact on neonatal brain injury.https://www.mdpi.com/2073-4409/14/11/818oxidative stressbrain injuryneuroprotectiondrugsnewborn infants
spellingShingle Virginia Beretta
Elena Scarpa
Silvia Carloni
Chiara Petrolini
Valentina Dell’Orto
Sebastiano Ravenda
Serafina Perrone
Antioxidant Bioactive Agents for Neuroprotection Against Perinatal Brain Injury
Cells
oxidative stress
brain injury
neuroprotection
drugs
newborn infants
title Antioxidant Bioactive Agents for Neuroprotection Against Perinatal Brain Injury
title_full Antioxidant Bioactive Agents for Neuroprotection Against Perinatal Brain Injury
title_fullStr Antioxidant Bioactive Agents for Neuroprotection Against Perinatal Brain Injury
title_full_unstemmed Antioxidant Bioactive Agents for Neuroprotection Against Perinatal Brain Injury
title_short Antioxidant Bioactive Agents for Neuroprotection Against Perinatal Brain Injury
title_sort antioxidant bioactive agents for neuroprotection against perinatal brain injury
topic oxidative stress
brain injury
neuroprotection
drugs
newborn infants
url https://www.mdpi.com/2073-4409/14/11/818
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AT chiarapetrolini antioxidantbioactiveagentsforneuroprotectionagainstperinatalbraininjury
AT valentinadellorto antioxidantbioactiveagentsforneuroprotectionagainstperinatalbraininjury
AT sebastianoravenda antioxidantbioactiveagentsforneuroprotectionagainstperinatalbraininjury
AT serafinaperrone antioxidantbioactiveagentsforneuroprotectionagainstperinatalbraininjury