International Journal of Molecular Sciences

Journal Browser

► Journal Browser

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 as well as 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 the 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 (2 papers)

Download All Papers

Research

21 pages, 8463 KiB

Open AccessArticle

Dysregulation of ErbB4 Signaling Pathway in the Dorsal Hippocampus after Neonatal Hypoxia-Ischemia and Late Deficits in PV⁺ Interneurons, Synaptic Plasticity and Working Memory

by Harisa Spahic, Pritika Parmar, Sarah Miller, Paul Casey Emerson, Charles Lechner, Mark St. Pierre, Neetika Rastogi, Michael Nugent, Sarah Ann Duck, Alfredo Kirkwood and Raul Chavez-Valdez

Int. J. Mol. Sci. 2023, 24(1), 508; https://doi.org/10.3390/ijms24010508 - 28 Dec 2022

Cited by 3 | Viewed by 2521

Abstract

Neonatal hypoxic-ischemic (HI) injury leads to deficits in hippocampal parvalbumin (PV)⁺ interneurons (INs) and working memory. Therapeutic hypothermia (TH) does not prevent these deficits. ErbB4 supports maturation and maintenance of PV⁺ IN. Thus, we hypothesized that neonatal HI leads to persistent deficits in PV⁺ INs, working memory and synaptic plasticity associated with ErbB4 dysregulation despite TH. P10 HI-injured mice were randomized to normothermia (NT, 36 °C) or TH (31 °C) for 4 h and compared to sham. Hippocampi were studied for α-fodrin, glial fibrillary acidic protein (GFAP), and neuroregulin (Nrg) 1 levels; erb-b2 receptor tyrosine kinase 4 (ErbB4)/ Ak strain transforming (Akt) activation; and PV, synaptotagmin (Syt) 2, vesicular-glutamate transporter (VGlut) 2, Nrg1, and ErbB4 expression in coronal sections. Extracellular field potentials and behavioral testing were performed. At P40, deficits in PV⁺ INs correlated with impaired memory and coincided with blunted long-term depression (LTD), heightened long-term potentiation (LTP) and increased Vglut2/Syt2 ratio, supporting excitatory-inhibitory (E/I) imbalance. Hippocampal Nrg1 levels were increased in the hippocampus 24 h after neonatal HI, delaying the decline documented in shams. Paradoxically ErbB4 activation decreased 24 h and again 30 days after HI. Neonatal HI leads to persistent deficits in hippocampal PV⁺ INs, memory, and synaptic plasticity. While acute decreased ErbB4 activation supports impaired maturation and survival after HI, late deficit reemergence may impair PV⁺ INs maintenance after HI. Full article

(This article belongs to the Special Issue Embracing the Diversity of Perinatal Brain Injury: Molecular Mechanisms and Novel Therapeutics 2022)

► Show Figures

Figure 1

13 pages, 1682 KiB

Open AccessArticle

Choline Improves Neonatal Hypoxia-Ischemia Induced Changes in Male but Not Female Rats

by Tayo Adeyemo, Ayodele Jaiyesimi, Jill G. Bumgardner, Charity Lohr, Aditi Banerjee, Mary C. McKenna and Jaylyn Waddell

Int. J. Mol. Sci. 2022, 23(22), 13983; https://doi.org/10.3390/ijms232213983 - 12 Nov 2022

Viewed by 1303

Abstract

Choline is an essential nutrient with many roles in brain development and function. Supplementation of choline in early development can have long-lasting benefits. Our experiments aimed to determine the efficacy of choline supplementation in a postnatal day (PND) 10 rat model of neonatal hypoxia ischemia (HI) at term using both male and female rat pups. Choline (100 mg/kg) or saline administration was initiated the day after birth and given daily for 10 or 14 consecutive days. We determined choline’s effects on neurite outgrowth of sex-specific cultured cerebellar granule cells after HI with and without choline. The magnitude of tissue loss in the cerebrum was determined at 72 h after HI and in adult rats. The efficacy of choline supplementation in improving motor ability and learning, tested using eyeblink conditioning, were assessed in young adult male and female rats. Overall, we find that choline improves neurite outgrowth, short-term histological measures and learning ability in males. Surprisingly, choline did not benefit females, and appears to exacerbate HI-induced changes. Full article

(This article belongs to the Special Issue Embracing the Diversity of Perinatal Brain Injury: Molecular Mechanisms and Novel Therapeutics 2022)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Embracing the Diversity of Perinatal Brain Injury: Molecular Mechanisms and Novel Therapeutics 2022

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (2 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI