ArticleThe Journal of clinical investigation2020
Pathogenesis of peritumoral hyperexcitability in an immunocompetent CRISPR-based glioblastoma model.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Surgical identification of brain tumour margins through impedance monitoring and electrocorticography and the potential for their combined use: A systematic review.Neurosurgical review · 2024Pooled it
- Decoding and Overcoming Temozolomide Resistance Through CRISPR/Cas Technologies.Molecular diagnosis & therapy · 2026Review
- Polyamines in CNS malignancies: positively charged culprits in the hijacking of neural and immune signaling pathways.Amino acids · 2026Review
- Spreading depolarization: A wave that precedes and drives cerebral ischemic cell death-Target for neuroprotection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Metabolic Reprogramming and Neurotransmitter Signaling Co-Option in the Glioma Immune Microenvironment: Dual-Axis Regulation of Immunosuppression.Biomolecules · 2026Review
- Transsynaptic tracing techniques to interrogate neuronal connectivity of glioblastomas.Nature protocols · 2026Review
- Tsunamis hiding in plain sight: spreading depression in clinical neurology.Nature reviews. Neurology · 2026Review
- Article
- Interhemispheric Functional Hypoconnectivity Is an Early Marker of Cortical Epileptogenesis.Biomedicines · 2026Article
- BOLD complexity characterizes glioblastoma survival via voxel-wise and localized sample entropy.Journal of neuro-oncology · 2026Article
- Aberrant neural activity in the peritumoral cortex underlies the progression of tumor-associated seizures.Nature communications · 2025Article
- Neuroscience in glioma biology (Review).Oncology reports · 2025Review
- WONOEP XVII appraisal: Targeting network excitability beyond the synapse -Neurotransmitter, ionic, and electro -diffusions.Epilepsia · 2025Review
- Cancer Neuroscience: Decoding Neural Circuitry in Tumor Evolution for Targeted Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Research progress in glioma-related epilepsy (Review).Biomedical reports · 2025Article
- Polyamine acetylation mediates crosstalk between cancer cells and myeloid cells to promote mesenchymal/plurimetabolic states in glioblastoma.Neuro-oncology · 2025Article
- The excitatory milieu in glioma: Mechanisms and therapeutic avenues.Neuro-oncology · 2025Review
- Early and widespread cerebellar engagement during hippocampal seizures and interictal discharges.Neurobiology of disease · 2025Article
- Deciphering transcriptomic changes in chemobrain: a comprehensive review.Acta neuropathologica communications · 2025Review
- The molecular landscape of glioblastoma-associated epilepsy.Journal of molecular medicine (Berlin, Germany) · 2025Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Seizures often herald the clinical appearance of gliomas or appear at later stages. Dissecting their precise evolution and cellular pathogenesis in brain malignancies could inform the development of staged therapies for these highly pharmaco-resistant epilepsies. Studies in immunodeficient xenograft models have identified local interneuron loss and excess glial glutamate release as chief contributors to network disinhibition, but how hyperexcitability in the peritumoral microenvironment evolves in an immunocompetent brain is unclear. We generated gliomas in WT mice via in utero deletion of key tumor suppressor genes and serially monitored cortical epileptogenesis during tumor infiltration with in vivo electrophysiology and GCAMP7 calcium imaging, revealing a reproducible progression from hyperexcitability to convulsive seizures. Long before seizures, coincident with loss of inhibitory cells and their protective scaffolding, gain of glial glutamate antiporter xCT expression, and reactive astrocytosis, we detected local Iba1+ microglial inflammation that intensified and later extended far beyond tumor boundaries. Hitherto unrecognized episodes of cortical spreading depolarization that arose frequently from the peritumoral region may provide a mechanism for transient neurological deficits. Early blockade of glial xCT activity inhibited later seizures, and genomic reduction of host brain excitability by deleting MapT suppressed molecular markers of epileptogenesis and seizures. Our studies confirmed xenograft tumor-driven pathobiology and revealed early and late components of tumor-related epileptogenesis in a genetically tractable, immunocompetent mouse model of glioma, allowing the complex dissection of tumor versus host pathogenic seizure mechanisms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.