Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
Embracing the Diversity of Perinatal Brain Injury: Molecular Mechanisms and...
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Embracing the Diversity of Perinatal Brain Injury: Molecular Mechanisms and Novel Therapeutics

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 (15 June 2022) | Viewed by 10894

Special Issue Editors

Dr. Lauren L. Jantzie

E-Mail Website
Guest Editor
Division of Neonatal-Perinatal Medicine, Department of Pediatrics and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Interests: perinatal brain injury; chorioamnionitis; posthemorrhagic hydrocephalus; pediatric traumatic brain injury; neuroinflammation; cerebral hypoxia-ischemia
Special Issues, Collections and Topics in MDPI journals
Dr. Raul Chavez-Valdez

E-Mail Website
Guest Editor
Johns Hopkins School of Medicine, Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Baltimore, MD 21205, USA
Interests: focus on the mechanisms of delayed injury and repair/regeneration in the developing brain following injury, specifically following neonatal hypoxic ischemic injury
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Perinatal brain injury (PBI) is one of the most important lifelong causes of epilepsy, cerebral palsy, and deficits in cognition, behavior, and social interaction. The challenges of diagnosing, treating, and managing PBI throughout the lifespan are rapidly evolving, especially as mortality following neonatal insults decreases and the burden of chronic disability increases. PBI includes, but is not limited to, hypoxic–ischemic encephalopathy (HIE), intraventricular hemorrhage, periventricular leukomalacia, and encephalopathy of prematurity. It affects both preterm and term neonates and is a reflection of diverse and complex etiologies and initiating insults. The pathophysiology of CNS injury following PBI reflects a combination of multiple insults, including (1) inflammation from prenatal infection and/or hypoxia–ischemia (HI); (2) individualized risk from genetic/congenital disorders; (3) acquired prenatal exposures to drugs, and toxins; (4) gut microbiota and nutritional status; and (5) postnatal stresses, such as sepsis and surgery. The cumulative effect of PBI results from a cascading impact on neurodevelopment and presents unique challenges to repair that are distinct from the mature CNS. While myelin, synapses, and circuits are plastic and modifiable throughout the lifespan, there remain many distinctive hurdles to repair of the developing brain. Notably, response to injury within the context of the constantly evolving, incompletely formed, platform of the developing CNS demands individualized and precision medicine approaches coupled with rigorous molecular and cellular mechanistic evaluation of the unique pathophysiology and mechanisms of disease.

Dr. Lauren L. Jantzie
Dr. Raul Chavez-Valdez
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.

Keywords

  • hypoxia–ischemia
  • chorioamnionitis
  • perinatal opioid exposure
  • perinatal alcohol exposure
  • seizures
  • neuroinflammation
  • excitotoxicity
  • GABAergic inhibition
  • hydrocephalus, neurorepair
  • neuroprotection

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

19 pages, 4299 KiB  
Article
Brain Tissue-Derived Extracellular Vesicle Mediated Therapy in the Neonatal Ischemic Brain
by Nam Phuong Nguyen, Hawley Helmbrecht, Ziming Ye, Tolulope Adebayo, Najma Hashi, My-Anh Doan and Elizabeth Nance
Int. J. Mol. Sci. 2022, 23(2), 620; https://doi.org/10.3390/ijms23020620 - 6 Jan 2022
Cited by 9 | Viewed by 3060
Abstract
Hypoxic-Ischemic Encephalopathy (HIE) in the brain is the leading cause of morbidity and mortality in neonates and can lead to irreparable tissue damage and cognition. Thus, investigating key mediators of the HI response to identify points of therapeutic intervention has significant clinical potential. [...] Read more.
Hypoxic-Ischemic Encephalopathy (HIE) in the brain is the leading cause of morbidity and mortality in neonates and can lead to irreparable tissue damage and cognition. Thus, investigating key mediators of the HI response to identify points of therapeutic intervention has significant clinical potential. Brain repair after HI requires highly coordinated injury responses mediated by cell-derived extracellular vesicles (EVs). Studies show that stem cell-derived EVs attenuate the injury response in ischemic models by releasing neuroprotective, neurogenic, and anti-inflammatory factors. In contrast to 2D cell cultures, we successfully isolated and characterized EVs from whole brain rat tissue (BEV) to study the therapeutic potential of endogenous EVs. We showed that BEVs decrease cytotoxicity in an ex vivo oxygen glucose deprivation (OGD) brain slice model of HI in a dose- and time-dependent manner. The minimum therapeutic dosage was determined to be 25 μg BEVs with a therapeutic application time window of 4–24 h post-injury. At this therapeutic dosage, BEV treatment increased anti-inflammatory cytokine expression. The morphology of microglia was also observed to shift from an amoeboid, inflammatory phenotype to a restorative, anti-inflammatory phenotype between 24–48 h of BEV exposure after OGD injury, indicating a shift in phenotype following BEV treatment. These results demonstrate the use of OWH brain slices to facilitate understanding of BEV activity and therapeutic potential in complex brain pathologies for treating neurological injury in neonates. Full article
(This article belongs to the Special Issue Embracing the Diversity of Perinatal Brain Injury: Molecular Mechanisms and Novel Therapeutics)
►▼ Show Figures

Graphical abstract

19 pages, 2383 KiB  
Article
Evaluating Neuroprotective Effects of Uridine, Erythropoietin, and Therapeutic Hypothermia in a Ferret Model of Inflammation-Sensitized Hypoxic-Ischemic Encephalopathy
by Kylie A. Corry, Olivia R. White, AnnaMarie E. Shearlock, Daniel H. Moralejo, Janessa B. Law, Jessica M. Snyder, Sandra E. Juul and Thomas R. Wood
Int. J. Mol. Sci. 2021, 22(18), 9841; https://doi.org/10.3390/ijms22189841 - 11 Sep 2021
Cited by 8 | Viewed by 2960
Abstract
Perinatal hypoxic-ischemic (HI) brain injury, often in conjunction with an inflammatory insult, is the most common cause of death or disability in neonates. Therapeutic hypothermia (TH) is the standard of care for HI encephalopathy in term and near-term infants. However, TH may not [...] Read more.
Perinatal hypoxic-ischemic (HI) brain injury, often in conjunction with an inflammatory insult, is the most common cause of death or disability in neonates. Therapeutic hypothermia (TH) is the standard of care for HI encephalopathy in term and near-term infants. However, TH may not always be available or efficacious, creating a need for novel or adjunctive neurotherapeutics. Using a near-term model of inflammation-sensitized HI brain injury in postnatal day (P) 17 ferrets, animals were randomized to either the control group (n = 43) or the HI-exposed groups: saline vehicle (Veh; n = 42), Ur (uridine monophosphate, n = 23), Epo (erythropoietin, n = 26), or TH (n = 24) to test their respective therapeutic effects. Motor development was assessed from P21 to P42 followed by analysis of cortical anatomy, ex vivo MRI, and neuropathology. HI animals took longer to complete the motor assessments compared to controls, which was exacerbated in the Ur group. Injury resulted in thinned white matter tracts and narrowed cortical sulci and gyri, which was mitigated in Epo-treated animals in addition to normalization of cortical neuropathology scores to control levels. TH and Epo treatment also resulted in region-specific improvements in diffusion parameters on ex vivo MRI; however, TH was not robustly neuroprotective in any behavioral or neuropathological outcome measures. Overall, Ur and TH did not provide meaningful neuroprotection after inflammation-sensitized HI brain injury in the ferret, and Ur appeared to worsen outcomes. By comparison, Epo appears to provide significant, though not complete, neuroprotection in this model. Full article
(This article belongs to the Special Issue Embracing the Diversity of Perinatal Brain Injury: Molecular Mechanisms and Novel Therapeutics)
►▼ Show Figures

Figure 1

Review

Jump to: Research

27 pages, 401 KiB  
Review
Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk
by Elisa Carloni, Adriana Ramos and Lindsay N. Hayes
Int. J. Mol. Sci. 2021, 22(23), 13035; https://doi.org/10.3390/ijms222313035 - 2 Dec 2021
Cited by 10 | Viewed by 4201
Abstract
Many types of stressors have an impact on brain development, function, and disease susceptibility including immune stressors, psychosocial stressors, and exposure to drugs of abuse. We propose that these diverse developmental stressors may utilize a common mechanism that underlies impaired cognitive function and [...] Read more.
Many types of stressors have an impact on brain development, function, and disease susceptibility including immune stressors, psychosocial stressors, and exposure to drugs of abuse. We propose that these diverse developmental stressors may utilize a common mechanism that underlies impaired cognitive function and neurodevelopmental disorders such as schizophrenia, autism, and mood disorders that can develop in later life as a result of developmental stressors. While these stressors are directed at critical developmental windows, their impacts are long-lasting. Immune activation is a shared pathophysiology across several different developmental stressors and may thus be a targetable treatment to mitigate the later behavioral deficits. In this review, we explore different types of prenatal and perinatal stressors and their contribution to disease risk and underlying molecular mechanisms. We highlight the impact of developmental stressors on microglia biology because of their early infiltration into the brain, their critical role in brain development and function, and their long-lived status in the brain throughout life. Furthermore, we introduce innate immune memory as a potential underlying mechanism for developmental stressors’ impact on disease. Finally, we highlight the molecular and epigenetic reprogramming that is known to underlie innate immune memory and explain how similar molecular mechanisms may be at work for cells to retain a long-term perturbation after exposure to developmental stressors. Full article
(This article belongs to the Special Issue Embracing the Diversity of Perinatal Brain Injury: Molecular Mechanisms and Novel Therapeutics)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop