Elevated glioma-related cortical glutamate in vivo is associated with ex vivo interictal discharges in human brain slices

Bodiabaduge Ashan P Jayasekera ^1,2, Jehill Parikh ³, Tamara Modebadze ¹

⁰Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.

Brain Communications +

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December 5, 2025

View abstract on PubMed

Summary

Elevated glutamate in the brain

Area Of Science

Neuroscience
Oncology
Biochemistry

Background

Gliomas, common malignant brain tumors, often cause seizures refractory to medication.
Identifying seizure-generating areas is crucial for improving surgical outcomes and reducing patient morbidity.
Previous studies on peri-tumoral glutamate levels and seizures in gliomas yielded inconclusive results.

Purpose Of The Study

To investigate the association between peri-tumoral glutamate levels and spontaneous interictal discharges (IIDs) in patients with supratentorial gliomas.
To explore the potential of magnetic resonance spectroscopy (MRS) as a biomarker for seizure-prone cortical regions.

Main Methods

Prospective observational study involving patients undergoing glioma surgery.
Pre-operative 1D MRS (Point Resolved Spectroscopy sequence) quantified peri-tumoral glutamate.
Ex vivo cortical local field potential (LFP) recordings assessed spontaneous IIDs.

Main Results

Peri-tumoral glutamate accumulation significantly correlated with the presence of spontaneous IIDs (P = 0.006).
Choline/creatine and N-acetyl aspartate/creatine ratios did not differ between IID and non-IID regions.
This suggests seizure susceptibility is independent of tumor infiltration or neuronal degeneration.

Conclusions

Peri-tumoral glutamate accumulation is a key metabolic marker linked to spontaneous IIDs in gliomas.
MRS shows promise as a non-invasive tool for identifying seizure-prone cortical areas.
Further validation is needed to integrate MRS into surgical planning and post-operative seizure management.

Keywords:

electrophysiology epilepsy glioma