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Journals
Biomedicines
Special Issues
Emerging Therapeutic Strategies for Epilepsy: Bridging Research and Clinical Practice
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Emerging Therapeutic Strategies for Epilepsy: Bridging Research and Clinical Practice

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 1116

Special Issue Editor

Dr. Tanveer Singh

E-Mail Website
Guest Editor
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 60801, USA
Interests: epilepsy; status epilepticus; MRI; EEG; inhibitory neurotransmission; immunohistochemistry; gene regulation; neurodegeneration; precision medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

This Special Issue is focused on advancing novel therapeutic strategies specifically for the treatment of epilepsy, a neurological disorder that remains a significant medical challenge. Epilepsy is characterized by recurrent, unprovoked seizures, and its complex pathophysiology involves genetic, molecular, and environmental factors. Despite advancements in understanding the mechanisms of epilepsy, current treatments often focus on managing symptoms rather than addressing the underlying causes, leaving many patients with limited options and persistent disability.

We invite leading researchers and clinicians to explore breakthroughs in epilepsy treatment, including the development of novel antiseizure medications, gene therapies, and innovative techniques such as neurostimulation. We specially emphasized translational research that bridges the gap between laboratory findings and clinical practice, with the goal of improving outcomes in patients with epilepsy. The issue will highlight emerging therapeutic approaches, such as precision medicine and neuroprotective agents, which offer potential for modifying the course of the disease rather than symptomatic relief.

By addressing key mechanisms such as neuronal hyperexcitability, synaptic dysfunction, and neuroinflammation, this issue seeks to advance our understanding of epileptogenesis and novel treatment strategies. The collection aims to inspire new research directions and foster hope for improved management and care for individuals living with epilepsy.

Dr. Tanveer Singh
Guest Editor

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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • epilepsy
  • status epilepticus
  • MRI
  • EEG
  • inhibitory neurotransmission
  • immunohistochemistry
  • gene regulation
  • neurodegeneration
  • precision medicine

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Published Papers (1 paper)

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Research

15 pages, 4094 KiB  
Article
Mossy Fiber Sprouting in Temporal Lobe Epilepsy: The Impact of Netrin-1, DCC, and Gene Expression Changes
by Melis Onay, Patrick N. Harter, Katherina Weber, Albrecht Piiper, Marcus Czabanka, Karl H. Plate, Thomas M. Freiman, Florian Gessler and Barbara Puhahn-Schmeiser
Biomedicines 2024, 12(12), 2869; https://doi.org/10.3390/biomedicines12122869 - 17 Dec 2024
Viewed by 948
Abstract
Background: Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy, often associated with hippocampal sclerosis (HS), which involves selective neuronal loss in the Cornu Ammonis subregion 1 CA1 and CA4 regions of the hippocampus. Granule cells show migration and mossy [...] Read more.
Background: Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy, often associated with hippocampal sclerosis (HS), which involves selective neuronal loss in the Cornu Ammonis subregion 1 CA1 and CA4 regions of the hippocampus. Granule cells show migration and mossy fiber sprouting, though the mechanisms remain unclear. Microglia play a role in neurogenesis and synaptic modulation, suggesting they may contribute to epilepsy. This study examines the role of microglia and axonal guidance molecules in neuronal reorganization in TLE. Methods: Nineteen hippocampal samples from patients with TLE undergoing epilepsy surgery were analyzed. Microglial activity (M1/M2-like microglia) and neuronal guidance molecules were assessed using microscopy and semi-automated techniques. Gene expression was evaluated using the nCounter Expression Profiling method. Results: Neuronal cell loss was correlated with decreased activity of the M1 microglial phenotype. In the CA2 region, neuronal preservation was linked to increased mossy fiber sprouting and microglial presence. Neuronal markers such as Deleted in Colorectal Cancer (DCC) and Synaptopodin were reduced in areas of cell death, while Netrin-1 was elevated in the granule cell layer, potentially influencing mossy fiber sprouting. The nCounter analysis revealed downregulation of genes involved in neuronal activity (e.g., NPAS4, BCL-2, GRIA1) and upregulation of IκB, indicating reduced neuroinflammation. Conclusions: This study suggests reduced neuroinflammation in areas of neuronal loss, while regions with preserved neurons showed mossy fiber sprouting associated with microglia, Netrin-1, and DCC. Full article
(This article belongs to the Special Issue Emerging Therapeutic Strategies for Epilepsy: Bridging Research and Clinical Practice)
►▼ Show Figures

Figure 1

Figure 1
<p>Subregions of healthy hippocampi (noHS) and sclerotic hippocampi (HS) stained with CD68. Activated microglia is recognizable by thickened and retracted branches. In the bar diagrams, bars and error bars indicate medians and IQR. (<b>A</b>) CA1 subregion of noHS. (<b>B</b>) CA1 subregion of HS. (<b>C</b>) CA2 subregion of noHS. (<b>D</b>) CA2 subregion of HS—here you can detect a significant overexpression of Iba-1. (<b>E</b>) CA3 subregion of noHS. (<b>F</b>) CA3 subregion of HS. (<b>G</b>) CA4 subregion of noHS. (<b>H</b>) CA4 subregion of HS. (<b>I</b>) Granule cell layer of noHS. (<b>J</b>) Granule cell layer of HS.</p> Full article ">Figure 2
<p>The levels of DCC in noHS and HS hippocampal slices. (<b>A</b>) Expression of DCC in noHS. (<b>B</b>) Expression of DCC in HS revealing a loss of DCC in all subregions. (<b>C</b>) One-factorial analysis of DCC-positive stained area/tissue area mm<sup>2</sup> in HS and noHS. The semi-automatized analysis shows a significant downregulation of DCC in subregion CA2, CA3, CA4, and GCL in the sclerotic tissue. Bars and error bars indicate medians and IQR. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001.</p> Full article ">Figure 3
<p>IHC staining of Netrin-1 in noHS and HS in hippocampal slices. (<b>A</b>) Expression of Netrin-1 in noHS (<b>B</b>) and in HS, displaying a loss of Netrin-1 in almost all subregions. (<b>C</b>) One-factorial analysis of Netrin-1-positive area/tissue area mm<sup>2</sup> in HS. A significant upregulation is detectable in the GCL region of HS. Bars and error bars indicate medians and IQR. ** <span class="html-italic">p</span> &lt; 0.01.</p> Full article ">Figure 4
<p>Cell type analyses according to the expression of different cell type scores in noHS and HS. For the investigation, six samples were used per group. Each point represents a sample. Boxes, bars and error bars indicate medians and IQR. The score is calculated from the cell type abundances by taking the logarithm of the expression of the genes specific to the cell types. (<b>A</b>) Astrocytes score (<b>B</b>) Oligodendrocytes score—An increased oligodendrocytes score (genes that occur in oligodendrocytes) is detectable in the sclerosis but there are no significant differences. (<b>C</b>) Microglia score—Surprisingly, an increased number of genes encoding for macrophages in general is apparent, even though the results are not significant. (<b>D</b>) Activated microglia score—The genes specifically associated with activated microglia exhibit higher expression in the noHS group, although without a significant result.</p> Full article ">Figure 5
<p>Differential levels of mRNAs and proteins between non-sclerotic (noHS) and sclerotic tissue (HS) are presented in volcano plots. (<b>A</b>) Differential levels of mRNAs and proteins involved in activated microglia. The largest differences were seen in the proteins NPAS4, FLT1, and BCL2, but none reached statistical significance. (<b>B</b>) Differential levels of cytokine mRNAs and proteins in HS and noHS. The highest differences were seen in VEGFA and FLT1, which, however, did not reach statistical significance. (<b>C</b>) Differential levels of mRNAs and proteins involved in vesicle trafficking. The highest differences are observed in NPAS4, ARC, KCNA1, and GRIA1; however, this did not reach statistical significance. (<b>D</b>) Differential levels of mRNAs involved in axon and dendrite structure in HS and noHS. The highest differences were seen in ARC, KCNA1, and GRIA1, again without reaching statistical significance.</p> Full article ">Figure 6
<p>Exemplary scheme of the expression of signaling influenced by cAMP in HS. The pathway was created by the summarization of pathway scores, which were calculated on the principal component analysis of the pathway genes’ normalized expression (refer to the <a href="#sec2-biomedicines-12-02869" class="html-sec">Section 2</a> for details). The mRNAs, which were found to be downregulated are blue colored, whereas upregulated mRNAs are gold colored. Interestingly, the expression of IκB was upregulated, which, in turn, leads to reduced activity of NFκB, as the NFκB pathway is inhibited by IκB. This could be interpreted as a sign of reduced neuroinflammation.</p> Full article ">
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