Cited by 3Tuberous Sclerosis Complex ResearchEpilepsy research and treatmentNeuroscience and Neuropharmacology Research

Iconography of abnormal non-neuronal cells in pediatric focal cortical dysplasia type IIb and tuberous sclerosis complex

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Zhang, Joyce, Argueta, Deneen, Tong, Xiaoping, Vinters, Harry V., Mathern, Gary W., Cepeda, Carlos·2025·Frontiers in Cellular Neuroscience

Abstract

Once believed to be the culprits of epileptogenic activity, the functional properties of balloon/giant cells (BC/GC), commonly found in some malformations of cortical development including focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC), are beginning to be unraveled. These abnormal cells emerge during early brain development as a result of a hyperactive mTOR pathway and may express both neuronal and glial markers. A paradigm shift occurred when our group demonstrated that BC/GC in pediatric cases of FCDIIb and TSC are unable to generate action potentials and lack synaptic inputs. Hence, their role in epileptogenesis remained obscure. In this review, we provide a detailed characterization of abnormal non-neuronal cells including BC/GC, intermediate cells, and dysmorphic/reactive astrocytes found in FCDIIb and TSC cases, with special emphasis on electrophysiological and morphological assessments. Regardless of pathology, the electrophysiological properties of abnormal cells appear more glial-like, while others appear more neuronal-like. Their morphology also differs in terms of somatic size, shape, and dendritic elaboration. A common feature of these types of non-neuronal cells is their inability to generate action potentials. Thus, despite their distinct properties and etiologies, they share a common functional feature. We hypothesize that, although the exact role of abnormal non-neuronal cells in FCDIIb and TSC remains mysterious, it can be suggested that cells displaying more glial-like properties function in a similar way as astrocytes do, i.e., to buffer K+ ions and neurotransmitters, while those with more neuronal properties, may represent a metabolic burden due to high energy demands but inability to receive or transmit electric signals. In addition, due to the heterogeneity of these cells, a new classification scheme based on morphological, electrophysiological, and gene/protein expression in FCDIIb and TSC cases seems warranted.

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Crossref · 10.3389/fncel.2024.1486315

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  • Tubers contain heterogeneous populations of dysmorphic neurons, dysplastic and gliotic astrocytes, activated microglia and giant or balloon cells within a background of normal-appearing cells.

    “On a cellular level, tubers contain heterogeneous populations of dysmorphic neurons, dysplastic and gliotic astrocytes, activated microglia and giant or balloon cells within a background of normal-appearing cells7,8,9.”

    From mTORC1 drives cell-autonomous astrocyte reactivity in tuberous sclerosis (2026) · cites this paper as [8]

    The 'Electrophysiological and morphological findings in ex vivo slices' section (page unavailable) describes TSC tissue as containing a heterogeneous range of dysplastic neurons, giant cells, and dysplastic or reactive astrocytes. The nomenclature section says microglia are affected in TSC but does not say they are activated; the cited paper also does not establish that these cells occur within a background of normal-appearing cells. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 1

  1. Castillo M. (2002). The Core curriculum: Neuroradiology: Lippincott Williams & Wilkins.

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Authors
Zhang, J., Argueta, D., Tong, X., Vinters, H. V., Mathern, G. W., & Cepeda, C.
Affiliations
  • University of California, Los Angeles (US)
  • Shanghai Jiao Tong University (CN)
Corresponding author
Cepeda, Carlos
Venue
Frontiers in Cellular Neuroscience
Published
2025-01-06
Volume
18
Pages
1486315-1486315
ISSN
1662-5102 (ISSN-L)
OpenAlex
W4406083066
Cited by
3
References
158
Citations by year
2026: 3
FWCI
0.39
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD103557)
Topics
  • Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
focal cortical dysplasia type IIb, tuberous sclerosis complex, balloon cells, giant cells, epileptogenesis, mTOR signaling, malformations of cortical development, intermediate cells, reactive astrocytes, action potential generation, cell classification, pediatric epilepsy

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