Altered glutamatergic and inflammatory pathways promote glioblastoma growth, invasion, and seizures: An overview

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Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain cancer. Drug-resistant seizures and cognitive impairments often accompany the invasion of the neocortex by the GBM cells. Recent studies suggest that seizures and glioma share common pathogenic mechanisms and may influence each other. One explanation for the close link between the two conditions is elevated glutamate in the tumor microenvironment (TME) due to an increased expression of the cystine-glutamate transporter with ensuing overactivity of glutamatergic signaling. Excess glutamate in the TME also encourages the polarization of pro-inflammatory tumor-associated macrophages to an anti-inflammatory state causing TME immunosuppression and facilitating tumor invasion. Besides, the recently discovered glutamatergic neurogliomal synapses, partially via their influence on calcium communication in microtube-connected tumor cell networks, drive the progression of GBM by stimulating glioma invasion and growth. Moreover, neuroinflammatory pathways have been shown to have several points of intersection with glutamatergic signaling in the TME, further promoting both epileptogenesis and oncogenesis. Future studies identifying pharmacotherapeutics targeting these elements is an extremely attractive therapeutic strategy for GBM, for which very little therapeutic progress has been made in the past two decades.

Original languageEnglish (US)
Article number120488
JournalJournal of the neurological sciences
StatePublished - Dec 15 2022


  • Brain-tumor
  • Glioblastoma
  • Glioma-neuron synapse
  • Glioma-related seizures
  • Glutamatergic pathway
  • Inflammation
  • Seizures

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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