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Brain Injury in the Newborn: The Present Status and Challenges...
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Brain Injury in the Newborn: The Present Status and Challenges in the Future

A special issue of Children (ISSN 2227-9067). This special issue belongs to the section "Pediatric Neurology & Neurodevelopmental Disorders".

Deadline for manuscript submissions: 10 September 2026 | Viewed by 1553

Special Issue Editor

Prof. Dr. Mark Dzietko

E-Mail Website
Guest Editor
Division of Neonatology, Department of General Pediatrics, Neonatology and Pediatric Cardiology, Heinrich-Heine University, 40225 Düsseldorf, Germany
Interests: neonatal neurology; perinatal brain injury; hypoxic–ischemic injury; stroke; neuroprotection; genetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hypoxic–ischemic brain injury remains a leading cause of neonatal mortality and long-term neurodevelopmental disabilities, primarily affecting the term-born population, although preterm infants may also be at risk. Despite remarkable advances in perinatal care, the diagnosis and therapy of neonatal brain injury remain a challenge, and therapies are largely supportive. The only established clinical intervention for hypoxic–ischemic brain injury is therapeutic hypothermia demonstrating reductions in risk of death or impairment. However, half of treated infants still suffer from major neurological problems such as cerebral palsy or epilepsy. Furthermore, in preterm infants, therapeutic hypothermia cannot be applied due to its side effects and insufficiency.

This Special Issue critically examines challenges in optimizing treatment and timing, improving access to care in low-resource settings, and addressing long-term outcomes. Additionally, the Issue highlights future directions, including precision medicine approaches, artificial intelligence in early diagnosis, and innovative rehabilitation methods. By integrating multidisciplinary perspectives, this Special Issue aims to bridge the gaps between research and clinical practice, serving as a comprehensive resource for clinicians and researchers and fostering improved outcomes for affected newborns worldwide.

Prof. Dr. Mark Dzietko
Guest Editor

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 250 words) can be sent to the Editorial Office for assessment.

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. Children is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). 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.

Keywords

  • brain
  • neuroprotection
  • encephalopathy
  • hypoxia ischemia
  • stroke
  • seizures
  • neuromonitoring
  • neuro-NICU

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Published Papers (2 papers)

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Research

12 pages, 698 KB  
Article
N-Acetylcysteine Reduces Tissue Injury Induced by Oxygen–Glucose Deprivation in an Organotypic Culture of Mouse Cerebral Cortex Slices
by Claudia Villani, Angelo Di Clemente, Roberto William Invernizzi and Rossano Rezzonico
Children 2026, 13(3), 379; https://doi.org/10.3390/children13030379 - 7 Mar 2026
Viewed by 538
Abstract
Background/Objectives: Hypoxic–ischemic encephalopathy is the leading cause of infant mortality and disability. Hypothermic therapy is effective in hypoxic–ischemic encephalopathy, albeit in a limited number of cases. Hypothermia requires advanced technologies and significant financial resources, which are difficult to sustain in low-income countries, with [...] Read more.
Background/Objectives: Hypoxic–ischemic encephalopathy is the leading cause of infant mortality and disability. Hypothermic therapy is effective in hypoxic–ischemic encephalopathy, albeit in a limited number of cases. Hypothermia requires advanced technologies and significant financial resources, which are difficult to sustain in low-income countries, with devastating consequences. Valid alternatives to hypothermia therapy are therefore needed. Methods: In vitro organotypic cultures of mouse cerebral cortex slices were used to demonstrate the direct protective effect of N-acetylcysteine (NAC) against brain tissue damage induced by oxygen–glucose deprivation (OGD), and to identify the concentrations and time window that maximize the drug’s effectiveness. NAC’s effectiveness was measured by the incorporation of propidium iodide (PI), a marker of cell membrane integrity. Results: Adding 0.1 and 1 mM NAC to the incubation medium before OGD strongly reduced OGD-induced PI incorporation, by 80% (p < 0.0002) and 89% (p < 0.0001), respectively. Administration of 1 mM NAC 1 h after OGD maintained a high degree of protection against OGD-induced damage (80% reduction in PI incorporation; p < 0.0001), while at 0.1 mM, the efficacy of NAC dropped to 44% (p < 0.005). Administration of NAC 4 h after OGD reduced PI incorporation to 52% (p < 0.005) at 1 mM, while at 0.1 mM, the effect was not significant (17%; p > 0.05). Exposure of slices to 0.1 and 1 mM NAC reduced PI incorporation in female cerebral cortex slices (p < 0.006), while only the higher concentration was effective in male slices (p < 0.05). Exposure to 0.1 mM NAC increased tissue levels of total glutathione (p = 0.0185), while no significant effect was observed with 1 mM NAC. Conclusions: This work highlights the direct effect of NAC in protecting cerebral cortex cells from OGD-induced damage and identifies the concentrations and time window that maximize the drug’s effect. The results underscore the need for further studies to verify the in vivo efficacy of NAC at concentrations found to be active in vitro, and for clinical trials to evaluate whether NAC can reduce hypoxia-induced brain damage in newborns. Full article
(This article belongs to the Special Issue Brain Injury in the Newborn: The Present Status and Challenges in the Future)
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16 pages, 819 KB  
Article
Differences in Management of Neonates with Hypoxic–Ischemic Encephalopathy (HIE) by Level of Neonatal Care Provided at Birth: Insights from a Referral-Based Cohort in the Canton of Zurich, Switzerland
by Ladina Erni, Ariane Pfister, Christian Haslinger, Michael Kleber, Barbara Brotschi, Dirk Bassler, Vinzenz Boos and Beate Grass
Children 2026, 13(1), 142; https://doi.org/10.3390/children13010142 - 19 Jan 2026
Viewed by 590
Abstract
Background/Objectives: Neonates with hypoxic–ischemic encephalopathy (HIE) are born in delivery facilities with different levels of neonatal care. The objective of this study was to investigate differences in the incidence of HIE and postnatal management between different levels of neonatal care in delivery [...] Read more.
Background/Objectives: Neonates with hypoxic–ischemic encephalopathy (HIE) are born in delivery facilities with different levels of neonatal care. The objective of this study was to investigate differences in the incidence of HIE and postnatal management between different levels of neonatal care in delivery facilities. Methods: This is a retrospective, multi-center cohort study of neonates with moderate-to-severe HIE receiving therapeutic hypothermia (TH) in the Canton of Zurich, Switzerland, registered in the Swiss National Asphyxia and Cooling Register between 2015 and 2023. Incidences of HIE receiving TH were calculated for all delivery facilities according to the national levels of neonatal care on site (Level I—basic; Level IIB—intermediate (no Level IIA facility in the Canton of Zurich); Level III—intensive neonatal care). Perinatal characteristics and variables on transport and outcomes were compared between neonates born in Level I and Level IIB facilities (the majority of the HIE population) and reported for neonates born in all other facilities (for completeness). Results: A total of 173 neonates (79 (45.7%) born in Level I; 80 (46.2%) in Level IIB; 9 (5.2%) in Level III; 5 (2.9%) in birthing centers) were admitted to a neonatal cooling center to receive TH. The average number of annual cases of HIE receiving TH per facility was 0.67 (0.11–1.50) in Level I and 2.22 (0.22–3.11) in Level IIB facilities (p = 0.088), respectively. There was no difference in Apgar score, worst pH (within 60 min after birth) and the severity of encephalopathy between neonates born in Level I and Level IIB facilities. Neonatal transport team requests were initiated earlier in Level I facilities (median 12 vs. 34 min of life, p < 0.001). There was no difference in age at initiation of TH (median 3 vs. 3 h, p = 0.431) and the time when target temperature was reached (median 4 vs. 4 h, p = 0.431) between neonates born in Level I and Level IIB facilities. Conclusions: The level of neonatal care available in delivery facilities influenced the management of neonates with HIE receiving TH. Full article
(This article belongs to the Special Issue Brain Injury in the Newborn: The Present Status and Challenges in the Future)
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