Novel Insights into Neuroinflammation and Related Diseases

A Special Issue of Cells (ISSN 2073-4409) belonging to the section "Cellular Neuroscience".

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 3628

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Guest Editor
Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, CA, USA
Interests: neuroscience; neuroinflammation; neuropsychological disorders; pathway analysis
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Special Issue Information

Dear Colleagues,

Neuroinflammation is a critical process in the pathogenesis of neuropsychological disorders, involving complex interactions between glial cells, neurons, and immune mediators. This Special Issue focuses on elucidating the cellular and molecular mechanisms underlying neuroinflammatory responses and their impact on affective and cognitive impairments. We welcome studies employing in vitro, in vivo, and in silico approaches to investigate neuroinflammation at the subcellular, cellular, and intercellular levels, with an emphasis on mechanistic insights.

Contributions should highlight novel experimental methodologies, molecular pathways, and cellular interactions that advance our understanding of neuroinflammation in disorders such as depression, anxiety, schizophrenia, and cognitive decline.

Topics of interest include, but are not limited to, the following:

  • Glial–neuronal crosstalk in neuroinflammatory signaling;
  • Molecular pathways (e.g., inflammasome activation, cytokine signaling) in affective and cognitive disorders;
  • In vitro, in vivo, and in silico models dissecting cellular and molecular mechanisms of neuroinflammation;
  • Microglia, astrocytes, and neuronal interactions in neuroinflammation;
  • Novel therapeutic strategies targeting neuroimmune mediators (e.g., small molecules, biologics, gene therapy);
  • Multi-omics approaches (transcriptomics, proteomics, metabolomics) to identify neuroinflammatory biomarkers;
  • Advanced imaging techniques (e.g., super-resolution microscopy, live-cell imaging) for studying neuroinflammation;
  • Cellular mechanisms of neuro–immune crosstalk in mood and cognitive dysfunction;
  • Mitochondrial dysfunction, autophagy, and apoptosis in neuroinflammatory contexts.

We encourage submissions (original research articles and comprehensive reviews) of experimental in vitro assays and in vivo studies, as well as in silico and computational approaches, to unravel neuroinflammatory mechanisms and therapeutic advances.

Dr. Tahmineh Mokhtari
Guest Editor

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Keywords

  • neuroinflammation
  • neuropsychological disorders
  • neurodegeneration
  • neuro-immune interactions
  • glial-neuronal crosstalk
  • autophagy and apoptosis
  • cellular and molecular mechanisms
  • neuroinflammatory biomarkers
  • imaging techniques
  • novel therapeutic strategies

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Published Papers (3 papers)

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Review

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24 pages, 1182 KB  
Review
Early Neuroimmune Modulation in Hereditary Cerebellar Ataxias: Experimental Opportunities in Zebrafish Models
by Valentina Naef, Michela Giacich, Devid Damiani and Filippo Maria Santorelli
Cells 2026, 15(11), 1014; https://doi.org/10.3390/cells15111014 - 31 May 2026
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Abstract
Hereditary cerebellar ataxias are progressive neurodegenerative disorders for which disease-modifying treatments remain lacking. Although these conditions have traditionally been investigated from a neuron-centered perspective, evidence from several ataxia models indicates that changes in the cerebellar immune microenvironment can arise before overt neuronal loss [...] Read more.
Hereditary cerebellar ataxias are progressive neurodegenerative disorders for which disease-modifying treatments remain lacking. Although these conditions have traditionally been investigated from a neuron-centered perspective, evidence from several ataxia models indicates that changes in the cerebellar immune microenvironment can arise before overt neuronal loss and may contribute to early circuit dysfunction. This review examines hereditary cerebellar ataxias through the lens of early neuroimmune regulation, with particular attention to the region-specific properties of cerebellar microglia and their roles in synaptic refinement, inflammatory tone modulation and circuit homeostasis. We further discuss zebrafish as a useful experimental system for this question, because they combine in vivo imaging, genetic manipulation, and scalable functional assays in an intact vertebrate model. In this context, flavonoids—and especially naringenin—are not considered as immediate therapeutic candidates, but as mechanistically informative experimental probes to investigate how modulation of neuroimmune signaling affects disease-relevant phenotypes in vivo. By integrating genetic ataxia models with dynamic neuroimmune readouts, functional behavioral assays, and circuit-level analyses, zebrafish-based approaches can help identify early windows during which neuroimmune signaling influences cerebellar resilience and disease progression and can guide subsequent validation in mammalian systems. Full article
(This article belongs to the Special Issue Novel Insights into Neuroinflammation and Related Diseases)
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26 pages, 2907 KB  
Review
Neuro-Immune Axis in Trauma-Induced Heterotopic Ossification: Mechanisms and Therapeutic Implications
by Oluomachukwu Jennifer Agu, Clifford Pereira, Ishaan Gupta, Ashley Moran and Tahmineh Mokhtari
Cells 2026, 15(9), 827; https://doi.org/10.3390/cells15090827 - 1 May 2026
Viewed by 714
Abstract
Trauma-induced heterotopic ossification (tHO) is characterized by aberrant ectopic bone formation in soft tissue following high-energy trauma, affecting >60% of combat-related amputees and >50% of major burn patients. Current prophylactic strategies (including NSAIDs, bisphosphonates, and low-dose radiation) lack mechanistic specificity, carry significant side [...] Read more.
Trauma-induced heterotopic ossification (tHO) is characterized by aberrant ectopic bone formation in soft tissue following high-energy trauma, affecting >60% of combat-related amputees and >50% of major burn patients. Current prophylactic strategies (including NSAIDs, bisphosphonates, and low-dose radiation) lack mechanistic specificity, carry significant side effects, and surgical excision carries a 27% recurrence rate. This review reframes tHO pathogenesis through the neural–immune axis, arguing that ectopic bone formation is a downstream consequence of dysregulated neuroimmune signaling rather than a primary osteogenic event. Following trauma, nociceptor activation drives nociception-induced neural inflammation (NINI), releasing substance P (SP) and calcitonin gene-related peptide (CGRP), which disrupts the blood–nerve barrier, mobilizes neural crest-derived progenitor cells, and, alongside BMP-2/SMAD1/5/8 signaling and M1-polarized macrophage activation, establishes a permissive osteogenic microenvironment. A BMP-2/CGRP positive feedback loop sustains aberrant osteogenesis, converging on osteogenic transcription factors Runx2, SOX5/6/9, and Osterix. Dysregulated noncoding RNAs represent promising pre-radiographic biomarkers. This neural–immune framework motivates mechanism-based therapeutic strategies targeting CGRP (fremanezumab, erenumab), SP/NK1 signaling (aprepitant), and macrophage polarization (metformin, palovarotene, rapamycin), with multi-node combination approaches tailored to the temporal stages of tHO offering the most promise for precision prophylaxis. Full article
(This article belongs to the Special Issue Novel Insights into Neuroinflammation and Related Diseases)
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Other

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26 pages, 925 KB  
Systematic Review
The Crossroads of Neuroinflammation and Biomarkers in Multiple Sclerosis: A Systematic Review
by Maria-Georgiana Gavrilă, Carmen Valeria Albu, Bogdan Cristian Albu, Emilia Burada, Raluca Elena Sandu and Roxana Surugiu
Cells 2026, 15(7), 610; https://doi.org/10.3390/cells15070610 - 30 Mar 2026
Cited by 4 | Viewed by 1710
Abstract
The management of multiple sclerosis (MS) is shifting from a phenotype-based framework toward a biologically driven precision medicine model, as conventional magnetic resonance imaging (MRI) inadequately captures smoldering inflammation and progression independent of relapse activity (PIRA). This systematic review aimed to synthesize current [...] Read more.
The management of multiple sclerosis (MS) is shifting from a phenotype-based framework toward a biologically driven precision medicine model, as conventional magnetic resonance imaging (MRI) inadequately captures smoldering inflammation and progression independent of relapse activity (PIRA). This systematic review aimed to synthesize current evidence on the diagnostic and prognostic utility of fluid biomarkers in distinguishing acute inflammatory injury from chronic neurodegeneration. A comprehensive search of Web of Science, PubMed, and Scopus (January 2020–September 2025) identified 28 eligible studies including 7775 participants (6365 MS patients and 1410 controls). Biomarkers derived from serum, plasma, cerebrospinal fluid (CSF), and stool were evaluated in relation to clinical disability measured using the Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) outcomes. Neurofilament light chain (NfL) consistently predicted acute inflammatory activity, gadolinium-enhancing lesions, and relapse-associated worsening, but levels were reduced by high-efficacy therapies and did not reliably predict PIRA. In contrast, glial fibrillary acidic protein (GFAP) was associated with astrogliosis, disability progression, and retinal thinning, even in patients with low inflammatory activity. Additional CSF, metabolic, and immunologic markers correlated with neurodegeneration and disease severity. Nevertheless, broader clinical use will require greater assay standardization, improved consistency across cohorts, and validation in prospective longitudinal studies. These findings compel a shift toward a multi-biomarker model to guide personalized therapeutic strategies and develop targeted neuroprotective treatments for progressive multiple sclerosis. Full article
(This article belongs to the Special Issue Novel Insights into Neuroinflammation and Related Diseases)
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