scholarly journals Could Perinatal Asphyxia Induce a Synaptopathy? New Highlights from an Experimental Model

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
María Inés Herrera ◽  
Matilde Otero-Losada ◽  
Lucas Daniel Udovin ◽  
Carlos Kusnier ◽  
Rodolfo Kölliker-Frers ◽  
...  
Keyword(s):  
Experimental Model ◽  
Neural Development ◽  
Neurological Disorders ◽  
Perinatal Asphyxia ◽  
Birth Asphyxia ◽  
Synaptic Connectivity ◽  
Synaptic Dysfunction ◽  
Preterm Neonates ◽  
Brain Structure And Function ◽  
And Function

Birth asphyxia also termed perinatal asphyxia is an obstetric complication that strongly affects brain structure and function. Central nervous system is highly susceptible to oxidative damage caused by perinatal asphyxia while activation and maturity of the proper pathways are relevant to avoiding abnormal neural development. Perinatal asphyxia is associated with high morbimortality in term and preterm neonates. Although several studies have demonstrated a variety of biochemical and molecular pathways involved in perinatal asphyxia physiopathology, little is known about the synaptic alterations induced by perinatal asphyxia. Nearly 25% of the newborns who survive perinatal asphyxia develop neurological disorders such as cerebral palsy and certain neurodevelopmental and learning disabilities where synaptic connectivity disturbances may be involved. Accordingly, here we review and discuss the association of possible synaptic dysfunction with perinatal asphyxia on the basis of updated evidence from an experimental model.

scholarly journals Microglia and astrocyte involvement in neurodegeneration and brain cancer

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Arthur A. Vandenbark ◽  
Halina Offner ◽  
Szymon Matejuk ◽  
Agata Matejuk
Keyword(s):  
Neurological Disorders ◽  
Neurological Diseases ◽  
The Body ◽  
Normal Brain ◽  
Key Factors ◽  
Therapeutic Outcomes ◽  
Brain Structure And Function ◽  
And Function ◽  
Different Origins ◽  
Frontotemporal Lobar Dementia

AbstractThe brain is unique and the most complex organ of the body, containing neurons and several types of glial cells of different origins and properties that protect and ensure normal brain structure and function. Neurological disorders are the result of a failure of the nervous system multifaceted cellular networks. Although great progress has been made in the understanding of glia involvement in neuropathology, therapeutic outcomes are still not satisfactory. Here, we discuss recent perspectives on the role of microglia and astrocytes in neurological disorders, including the two most common neurodegenerative conditions, Alzheimer disease and progranulin-related frontotemporal lobar dementia, as well as astrocytoma brain tumors. We emphasize key factors of microglia and astrocytic biology such as the highly heterogeneic glial nature strongly dependent on the environment, genetic factors that predispose to certain pathologies and glia senescence that inevitably changes the CNS landscape. Our understanding of diverse glial contributions to neurological diseases can lead advances in glial biology and their functional recovery after CNS malfunction.

scholarly journals Symmetry breaking of hPSCs in micropattern generates a polarized spinal cord-like organoid (pSCO) with dorsoventral organization

2021 ◽  
Author(s):  
Kyubin Seo ◽  
Subin Cho ◽  
Ju-Hyun Lee ◽  
June Hoan Kim ◽  
Boram Lee ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cell Differentiation ◽  
Symmetry Breaking ◽  
Neural Development ◽  
Early Embryo ◽  
Cell Patterning ◽  
Axis Formation ◽  
Brain Structure And Function ◽  
Brain Organoid ◽  
And Function

Brain organoid research is advancing, but generation of organoids with proper axis formation, which could lead to spatially ordered structures for complex brain structure and function, still remains a challenge. Axis formation and related spatial cell organization in the CNS are initiated by the symmetry breaking during the early embryo development. It has been demonstrated that the geometrically confined culture of human pluripotent stem cells (hPSCs) can be used to induce symmetry breaking and regionalized cell differentiation. In this study, we generated a polarized spinal cord organoid with a self-organized dorsoventral (DV) organization, using 2D cell patterning by geometric confinement. Initially, the application of caudalization signals to hPSCs promoted the regionalized cell differentiation along the radial axis and sprouting-like protrusion morphogenesis in cell colonies confined to ECM protein micropatterns. Detachment of colonies turned them into extended spinal cord-like organoids which maintained center- and edge-derived two poles. Further analyses including single cell RNA sequencing and spatial transcriptome analysis unveiled that these organoids contained rich repertoire of developing spinal cord cells and exhibited the spatially ordered DV domain formation along the long axis without external organizing signals. Modulation of BMP and Shh signaling can control the extent of DV coverage in organoids following the principles of embryo patterning. Our study provides a simple, and precisely controllable method to generate spatially-ordered organoids for understanding of biological principles of cell patterning and axis formation during neural development.

scholarly journals Diversity and Function of Somatostatin-Expressing Interneurons in the Cerebral Cortex

2019 ◽  
Vol 20 (12) ◽  
pp. 2952 ◽  
Author(s):  
Therese Riedemann
Keyword(s):  
Major Depressive Disorder ◽  
Cerebral Cortex ◽  
Depressive Disorder ◽  
Neurological Disorders ◽  
Synaptic Connectivity ◽  
Inhibitory Interneurons ◽  
Cortical Circuits ◽  
Major Depressive ◽  
Neuron Population ◽  
And Function

Inhibitory interneurons make up around 10–20% of the total neuron population in the cerebral cortex. A hallmark of inhibitory interneurons is their remarkable diversity in terms of morphology, synaptic connectivity, electrophysiological and neurochemical properties. It is generally understood that there are three distinct and non-overlapping interneuron classes in the mouse neocortex, namely, parvalbumin-expressing, 5-HT3A receptor-expressing and somatostatin-expressing interneuron classes. Each class is, in turn, composed of a multitude of subclasses, resulting in a growing number of interneuron classes and subclasses. In this review, I will focus on the diversity of somatostatin-expressing interneurons (SOM+ INs) in the cerebral cortex and elucidate their function in cortical circuits. I will then discuss pathological consequences of a malfunctioning of SOM+ INs in neurological disorders such as major depressive disorder, and present future avenues in SOM research and brain pathologies.

scholarly journals Early Acute Kidney Injury in Preterm and Term Neonates: Incidence, Outcome, and Associated Clinical Features

Neonatology ◽  
2021 ◽  
pp. 1-6
Author(s):  
Dario Gallo ◽  
Karen A. de Bijl-Marcus ◽  
Thomas Alderliesten ◽  
Marc Lilien ◽  
Floris Groenendaal
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Perinatal Asphyxia ◽  
Neurodevelopmental Outcome ◽  
Birth Asphyxia ◽  
Kidney Injury ◽  
Preterm Neonates ◽  
Term Infants

<b><i>Background:</i></b> Critically ill neonates are at high risk of kidney injury, mainly in the first days of life. Acute kidney injury (AKI) may be underdiagnosed due to lack of a uniform definition. In addition, long-term renal follow-up is limited. <b><i>Objective:</i></b> To describe incidence, etiology, and outcome of neonates developing AKI within the first week after birth in a cohort of NICU-admitted neonates between 2008 and 2018. Renal function at discharge in infants with early AKI was assessed. <b><i>Methods and Subjects:</i></b> AKI was defined as an absolute serum Cr (sCr) value above 1.5 mg/dL (132 μmol/L) after the first 24 h or as stage 2–3 of the NIDDK neonatal definition. Clinical data and outcomes were collected from medical records and retrospectively analyzed. <b><i>Results:</i></b> From January 2008 to December 2018, a total of 9,376 infants were admitted to the NICU of Wilhelmina Children’s Hospital/UMC Utrecht, of whom 139 were diagnosed with AKI during the first week after birth. In 72 term infants, the most common etiology was perinatal asphyxia (72.2%), followed by congenital kidney and urinary tract malformations (CAKUT) (8.3%), congenital heart disease (6.9%), and sepsis (2.8%). Associated conditions in 67 preterm infants were medical treatment of a hemodynamic significant PDA (27.2%), ­CAKUT (21%), and birth asphyxia (19.4%). Among preterm neonates and neonates with perinatal asphyxia, AKI was mainly diagnosed by the sCr &#x3e;1.5 mg/dL criterion. Renal function at discharge improved in 76 neonates with AKI associated with acquired conditions. Neonates with stage 3 AKI showed increased sCr values at discharge. Half of these were caused by congenital kidney malformations and evolved into chronic kidney disease (CKD) later in life. Neurodevelopmental outcome (NDO) at 2 years was favorable in 93% of surviving neonates with detailed follow-up. <b><i>Conclusion:</i></b> During the first week after birth, AKI was seen in 1.5% of infants admitted to a level III NICU. Renal function at discharge had improved in most neonates with acquired AKI but not in infants diagnosed with stage 3 AKI. Long-term renal function needs further exploration, whereas NDO appears to be good.

scholarly journals Astroglial Hemichannels and Pannexons: The Hidden Link between Maternal Inflammation and Neurological Disorders

2021 ◽  
Vol 22 (17) ◽  
pp. 9503
Author(s):  
Juan Prieto-Villalobos ◽  
Tanhia F. Alvear ◽  
Andrés Liberona ◽  
Claudia M. Lucero ◽  
Claudio J. Martínez-Araya ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Neuronal Damage ◽  
Redox Homeostasis ◽  
Harmful Effect ◽  
Brain Dysfunction ◽  
Autism Spectrum ◽  
Maternal Inflammation ◽  
Brain Structure And Function ◽  
Prenatal Inflammation ◽  
And Function

Maternal inflammation during pregnancy causes later-in-life alterations of the offspring’s brain structure and function. These abnormalities increase the risk of developing several psychiatric and neurological disorders, including schizophrenia, intellectual disability, bipolar disorder, autism spectrum disorder, microcephaly, and cerebral palsy. Here, we discuss how astrocytes might contribute to postnatal brain dysfunction following maternal inflammation, focusing on the signaling mediated by two families of plasma membrane channels: hemi-channels and pannexons. [Ca2+]i imbalance linked to the opening of astrocytic hemichannels and pannexons could disturb essential functions that sustain astrocytic survival and astrocyte-to-neuron support, including energy and redox homeostasis, uptake of K+ and glutamate, and the delivery of neurotrophic factors and energy-rich metabolites. Both phenomena could make neurons more susceptible to the harmful effect of prenatal inflammation and the experience of a second immune challenge during adulthood. On the other hand, maternal inflammation could cause excitotoxicity by producing the release of high amounts of gliotransmitters via astrocytic hemichannels/pannexons, eliciting further neuronal damage. Understanding how hemichannels and pannexons participate in maternal inflammation-induced brain abnormalities could be critical for developing pharmacological therapies against neurological disorders observed in the offspring.

Study of Myocardial Dysfunction in Perinatal Asphyxia Field

2018 ◽  
Vol 2 (S1) ◽  
pp. e000127
Author(s):  
Kushali Tanna ◽  
K M Mehariya ◽  
Suchita Munsi ◽  
Charul Pujani
Keyword(s):  
Troponin I ◽  
Heart Diseases ◽  
Perinatal Asphyxia ◽  
Myocardial Dysfunction ◽  
Birth Asphyxia ◽  
Serum Levels ◽  
Spontaneous Respiration ◽  
Term Neonates ◽  
Myocardial Involvement ◽  
Ischemic Encephalopathy

Aims and Objectives: To study an incidence of myocardial dysfunction in neonates admitted with perinatal asphyxia, to find out its correlation with severity of birth asphyxia and its outcome. Methods: This prospective study was conducted among 40 term neonates admitted in NICU of Civil Hospital Ahmedabad who had suffered with perinatal asphyxia (defined by WHO ), resuscitated as per NRP guidelines-2015 including both intramural and extramural admissions and who developed to hypoxic ischemic encephalopathy as defined by Levene staging. Neonates with congenital heart diseases, major central nervous system malformations and neonatal sepsis were excluded. Myocardial involvement was assessed by clinical evaluation, ECG, Creatinine Kinase Total (25-200IU/L), CK-MB (0-25IU/L) and Troponin I (0-0.03ug/L) measurements. Results: Among 40 cases, 10(25%) neonates had moderate birth asphyxia while 30(75%) had severe birth asphyxia. Respiratory distress was observed in 34(77.5%), poor spontaneous respiration 4(10%),shock in 14(35%),CCF 19(47.5%) while ECG was abnormal in 30(76.7%). Serum levels of CPK Total, CPK- MB and Troponin I were raised in 34(85%), 32(80%) and 28 (70%) neonates, respectively.  Conclusion: There was a direct correlation between ECG changes and enzymatic levels which showed increasing abnormalities with increasing with severity of HIE.  

The ENIGMA Brain Injury Working Group: Approach, Challenges, and Potential Benefits

2019 ◽  
Author(s):  
Elisabeth A. Wilde ◽  
Emily L. Dennis ◽  
David F Tate
Keyword(s):  
Brain Injury ◽  
Working Group ◽  
Meta Analysis ◽  
Special Issue ◽  
Group Approach ◽  
Challenges And Opportunities ◽  
Brain Structure And Function ◽  
Potential Benefits ◽  
And Function ◽  
Neuroimaging Genetics

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium brings together researchers from around the world to try to identify the genetic underpinnings of brain structure and function, along with robust, generalizable effects of neurological and psychiatric disorders. The recently-formed ENIGMA Brain Injury working group includes 8 subgroups, based largely on injury mechanism and patient population. This introduction to the special issue summarizes the history, organization, and objectives of ENIGMA Brain Injury, and includes a discussion of strategies, challenges, opportunities and goals common across 6 of the subgroups under the umbrella of ENIGMA Brain Injury. The following articles in this special issue, including 6 articles from different subgroups, will detail the challenges and opportunities specific to each subgroup.

scholarly journals Cadherins in early neural development

2021 ◽  
Author(s):  
Karolina Punovuori ◽  
Mattias Malaguti ◽  
Sally Lowell
Keyword(s):  
Adhesion Molecules ◽  
Cell Fate ◽  
Neural Development ◽  
Ex Vivo ◽  
Directed Differentiation ◽  
Culture Dish ◽  
Cell Identity ◽  
Cell Fate Decisions ◽  
Neural Tissues ◽  
And Function

AbstractDuring early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why are differentiation and adhesion so tightly linked? It is now over 60 years since Conrad Waddington noted the remarkable "Constancy of the Wild Type” (Waddington in Nature 183: 1654–1655, 1959) yet we still do not fully understand the mechanisms that make development so reproducible. Conversely, we do not understand why directed differentiation of cells in a dish is sometimes unpredictable and difficult to control. It has long been suggested that cells make decisions as 'local cooperatives' rather than as individuals (Gurdon in Nature 336: 772–774, 1988; Lander in Cell 144: 955–969, 2011). Given that the cadherin family of adhesion molecules can simultaneously influence morphogenesis and signalling, it is tempting to speculate that they may help coordinate cell fate decisions between neighbouring cells in the embryo to ensure fidelity of patterning, and that the uncoupling of these processes in a culture dish might underlie some of the problems with controlling cell fate decisions ex-vivo. Here we review the expression and function of cadherins during early neural development and discuss how and why they might modulate signalling and differentiation as neural tissues are formed.

scholarly journals Advancing Drug Discovery for Neurological Disorders Using iPSC-Derived Neural Organoids

2021 ◽  
Vol 22 (5) ◽  
pp. 2659
Author(s):  
Gianluca Costamagna ◽  
Giacomo Pietro Comi ◽  
Stefania Corti
Keyword(s):  
Drug Discovery ◽  
Drug Screening ◽  
Neural Development ◽  
Neurological Disorders ◽  
Large Scale ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Cellular Level ◽  
Complex Data ◽  
Complex Data Sets

In the last decade, different research groups in the academic setting have developed induced pluripotent stem cell-based protocols to generate three-dimensional, multicellular, neural organoids. Their use to model brain biology, early neural development, and human diseases has provided new insights into the pathophysiology of neuropsychiatric and neurological disorders, including microcephaly, autism, Parkinson’s disease, and Alzheimer’s disease. However, the adoption of organoid technology for large-scale drug screening in the industry has been hampered by challenges with reproducibility, scalability, and translatability to human disease. Potential technical solutions to expand their use in drug discovery pipelines include Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) to create isogenic models, single-cell RNA sequencing to characterize the model at a cellular level, and machine learning to analyze complex data sets. In addition, high-content imaging, automated liquid handling, and standardized assays represent other valuable tools toward this goal. Though several open issues still hamper the full implementation of the organoid technology outside academia, rapid progress in this field will help to prompt its translation toward large-scale drug screening for neurological disorders.

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