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The Function of Glial Cells in the Nervous System: 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 May 2026 | Viewed by 3851

Special Issue Editor

Dr. Krista Minéia Wartchow

E-Mail Website
Guest Editor
Brain Health Imaging Institute, Department of Radiology, Weill Cornell Medicine, New York, NY 10044, USA
Interests: astroglial cells; glial–neuronal interaction in synapses; biomarkers; S100B; Alzheimer’s disease; cognition
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue on “The Function of Glial Cells in the Nervous System”.

In nervous system homeostasis, glial cells, or neuroglia, play a collective role. Essentially all aspects of the nervous system's formation and function are orchestrated by the diverse and dynamic functions of glial cells. These include forming synapses, regulating synaptic transmission and plasticity, maintaining redox balance, maintaining ion and water homeostasis, establishing the blood–brain barrier, controlling toxicity in the extracellular space, and establishing myelin sheets. Furthermore, these cells play a crucial role in immune and inflammatory functions in pathological conditions, contributing to both healthy and diseased states with neurological outcomes. In this regard, a major objective of this Special Issue is to collect studies and reviews on glial cells and the glial–neuronal interaction rearrangements that occur during aging or in neurodegenerative diseases, possible glial biomarkers, as well as studies on therapeutic approaches with which to counteract these compromised mechanisms.

Dr. Krista Minéia Wartchow
Guest Editor

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Keywords

  • glial cells
  • glial–neuronal interaction
  • glial biomarkers
  • neurodegenerative diseases
  • therapeutic approaches

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Related Special Issue

Published Papers (3 papers)

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Research

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34 pages, 17016 KB  
Article
Investigation of the Expression, Localization, and Acidosis-Associated Conformational Changes in Connexin 43 in Traumatic Brain Injury with the Development of a Neural Network Model for Assessing Systemic Inflammation
by Chizaram Nwosu, Evgeniya Kirichenko, Stanislav Bachurin, Mikhail Petrushan, Alexey Ermakov, Rozaliia Nabiullina, Marya Kaplya, Alexander Logvinov and Stanislav Rodkin
Int. J. Mol. Sci. 2025, 26(18), 8855; https://doi.org/10.3390/ijms26188855 - 11 Sep 2025
Viewed by 633
Abstract
Traumatic brain injury (TBI) is one of the most common forms of neurotrauma, accompanied by significant disruptions in neuronal homeostasis and intercellular communication. A key protein involved in these processes is connexin 43 (Cx43), which facilitates the formation of gap junctions in the [...] Read more.
Traumatic brain injury (TBI) is one of the most common forms of neurotrauma, accompanied by significant disruptions in neuronal homeostasis and intercellular communication. A key protein involved in these processes is connexin 43 (Cx43), which facilitates the formation of gap junctions in the astrocytic network. In this study, using confocal and immunofluorescence microscopy, ultrastructural analysis, and molecular modeling, we investigated the dynamics of Cx43 expression and structural changes in neuroglia during various post-traumatic periods following TBI. It was shown that in the acute phase, 24 h post-injury, there is a reduction in Cx43 expression, accompanied by apoptotic neuronal degradation, disruption of nuclear NeuN localization, and destruction of cellular ultrastructure. By 7 days post-injury, a significant increase in Cx43 levels was observed, along with the formation of protein aggregates associated with pronounced reactive astrogliosis. Peripheral blood analysis revealed persistent neutrophilia, lymphopenia, and reduced monocyte levels, reflecting a systemic inflammatory response and immunosuppression, which was corroborated by a custom-trained neural network-based computer vision model. Linear regression and correlation analyses further identified a strong positive association between normalized monocyte levels and Cx43 expression, a moderate negative correlation with lymphocytes, and no significant correlation with neutrophils. Using a custom-built computer vision model, we confirmed these hematological trends and detected subtle changes, such as early increases in platelet counts, that were not captured by manual evaluation. The model demonstrated strong performance in classifying common blood cell types and proved to be a valuable tool for monitoring dynamic post-traumatic shifts in blood. Molecular dynamics modeling of Cx43 identified a pH-dependent mechanism of conformational reorganization under post-traumatic acidosis, mediated by the interaction between protonated His142 and Glu103. This mechanism mimics the structural consequences of the pathogenic E103K mutation and may play a critical role in the neurotoxic effects of Cx43 in TBI. These findings highlight the complexity of Cx43 regulation under traumatic conditions and its potential significance as a target for neuroprotective therapy. Full article
(This article belongs to the Special Issue The Function of Glial Cells in the Nervous System: 2nd Edition)
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Review

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27 pages, 3143 KB  
Review
Diversity, Functional Complexity, and Translational Potential of Glial Cells in the Central Nervous System
by Agata Wawrzyniak, Izabela Krawczyk-Marć, Agnieszka Żuryń, Jerzy Walocha and Krzysztof Balawender
Int. J. Mol. Sci. 2025, 26(18), 9080; https://doi.org/10.3390/ijms26189080 - 18 Sep 2025
Viewed by 1835
Abstract
Glial cells have emerged as active and dynamic regulators of central nervous system (CNS) function, far beyond their historically perceived supportive role. This review synthesizes the most recent advances in glial biology, highlighting novel molecular mechanisms, cutting-edge imaging methodologies, and translational strategies that [...] Read more.
Glial cells have emerged as active and dynamic regulators of central nervous system (CNS) function, far beyond their historically perceived supportive role. This review synthesizes the most recent advances in glial biology, highlighting novel molecular mechanisms, cutting-edge imaging methodologies, and translational strategies that redefine their role in health and disease. We emphasize new findings on astrocytic signaling in neurodegeneration, NG2-glia dynamics, and microglial modulation, providing forward-looking perspectives for glia-targeted therapeutic interventions. Recent breakthroughs in high-resolution in vivo imaging, single-cell transcriptomics, and gene-editing platforms are discussed in the context of their ability to unravel glial heterogeneity and functional plasticity. By integrating molecular insights with translational research, this review aims to bridge the gap between basic neuroscience and clinical applications, offering a framework for next-generation CNS therapies. Full article
(This article belongs to the Special Issue The Function of Glial Cells in the Nervous System: 2nd Edition)
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18 pages, 3034 KB  
Review
The Astroglia Syncytial Theory of Consciousness
by James M. Robertson
Int. J. Mol. Sci. 2025, 26(12), 5785; https://doi.org/10.3390/ijms26125785 - 17 Jun 2025
Cited by 1 | Viewed by 1043
Abstract
The neurological basis of consciousness remains unknown despite innumerable theories proposed for over a century. The major obstacle is that empirical studies demonstrate that all sensory information is subdivided and parcellated as it is processed within the brain. A central region where such [...] Read more.
The neurological basis of consciousness remains unknown despite innumerable theories proposed for over a century. The major obstacle is that empirical studies demonstrate that all sensory information is subdivided and parcellated as it is processed within the brain. A central region where such diverse information combines to form conscious expression has not been identified. A novel hypothesis was introduced over two decades ago that proposed astrocytes, with their ability to interconnect to form a global syncytium within the neocortex, are the locus of consciousness based on their ability to integrate synaptic signals. However, it was criticized because intercellular calcium waves, which are initiated by synaptic activity, are too slow to contribute to consciousness but ideal for memory formation. Although astrocytes are known to exhibit rapid electrical responses in active sensory pathways (e.g., vision), it was technically impossible to determine electrical activity within the astroglia syncytium because of the challenge of separating syncytial electrical responses from simultaneous neuronal electrical activity. Therefore, research on astroglia syncytial electrical activity lagged for over sixty years, until recently, when an ingenuous technique was developed to eliminate neuronal electrical interference. These technical advances have demonstrated that the astroglia syncytium, although massive and occupying the entire neocortex, is isoelectric with minimal impedance. Most importantly, the speed of electrical conductance within the syncytium is as rapid as that of neural networks. Therefore, the astroglia syncytium is theoretically capable of transmitting integrated local synaptic signaling globally throughout the entire neocortex to bind all functional areas of the brain in a timeframe required for consciousness. Full article
(This article belongs to the Special Issue The Function of Glial Cells in the Nervous System: 2nd Edition)
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