ArticleScience translational medicine2014
Cortical GABAergic excitation contributes to epileptic activities around human glioma.
Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers, 1 of them a synthesis that pooled it.
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Who cites it
151 citing papers in PubMed, 1 synthesis or guideline pooled it, 290 citations in OpenAlex.
- Impact of levetiracetam use in glioblastoma: an individual patient-level meta-analysis assessing overall survival.Neurosurgical review · 2024Pooled it
- Pilot Trial of Perampanel on Peritumoral Hyperexcitability in Newly Diagnosed High-grade Glioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders.Translational psychiatry · 2017Trial
- HBQ1 Acts as a Prognostic Biomarker and Tumor Suppressor Linked to Antigen Presentation in Glioma.Cell biochemistry and function · 2026Article
- Adaptive Network Stabilization Despite Profound Structural Reorganization in Human Organotypic Cultures.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Enhancing KCC2 function reduces interictal activity and prevents seizures in temporal lobe epilepsy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Electrophysiologically Targeted Biopsies Reveal the Transcriptional Landscape of Focal Epilepsy.bioRxiv : the preprint server for biology · 2026Article
- Article
- Aberrant neural activity in the peritumoral cortex underlies the progression of tumor-associated seizures.Nature communications · 2025Article
- Small cell lung cancer induces synaptic scaling to alter neuronal excitability.Communications biology · 2025Article
- Novel GABAAR antagonists target networked gene hubs at the leading edge in high-grade gliomas.Neuro-oncology · 2025Article
- Epileptogenic LGG surgery with seizure freedom purpose: Supratotal resection (ETT-SpTR) based on Electrocorticography and navigated transcranial magnetic stimulation.Acta neurochirurgica · 2025Article
- Research progress in glioma-related epilepsy (Review).Biomedical reports · 2025Article
- Tumor-related epilepsy in glioma: A multidisciplinary overview.Epilepsia · 2025Review
- The excitatory milieu in glioma: Mechanisms and therapeutic avenues.Neuro-oncology · 2025Review
- Differentiation of tumor versus peritumoral cortex in gliomas by intraoperative electrocorticography.Neuro-oncology · 2025Article
- Localization of the Epileptogenic Zone Using Neural Spatial Volatility in Epilepsy Surgery.Neurology · 2025Observational
- Flexible 3D Kirigami Probes for In Vitro and In Vivo Neural Applications.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- Article
- Association between Levetiracetam Use and Survival in Patients with Glioblastoma: A Nationwide Population-Based Study.Cancer research and treatment · 2025Article
91 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
Brain gliomas are highly epileptogenic. Excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glioma cells. Thus, the contribution of γ-aminobutyric acidergic (GABAergic) mechanisms that depend on intracellular chloride merits closer study. We studied the occurrence, networks, cells, and signaling basis of epileptic activities in neocortical slices from the peritumoral surgical margin resected around human brain gliomas. Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges, synchronized, with a high-frequency oscillation signature, in superficial layers of neocortex around areas of glioma infiltration. Interictal-like events depended both on glutamatergic AMPA receptor-mediated transmission and on depolarizing GABAergic signaling. GABA released by interneurons depolarized 65% of pyramidal cells, in which chloride homeostasis was perturbed because of changes in expression of neuronal chloride cotransporters: KCC2 (K-Cl cotransporter 2) was reduced by 42% and expression of NKCC1 (Na-K-2Cl cotransporter 1) increased by 144%. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. This study shows that epileptic activities are sustained by excitatory effects of GABA in human peritumoral neocortex, as reported in temporal lobe epilepsies, suggesting that both glutamate and GABA signaling and cellular chloride regulation processes, all also involved in oncogenesis as already shown, induce an imbalance between synaptic excitation and inhibition underlying epileptic discharges in glioma patients. Thus, the control of chloride in neurons and glioma cells may provide a therapeutic target for patients with epileptogenic gliomas.
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Registered trials
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.