Glioblastoma-induced neuronal excitability dysfunction in human brain tissue: tumor-driven electrophysiological, morphological, and molecular alterations of the peritumoral microenvironment.

• Applicants: Privatdozent Dr. Daniel Delev; Danqing Yang, Ph.D.
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 557599297

Glioblastoma is one of the most common and devastating malignant brain tumors with an extremely poor prognosis, which is resembled by an overall survival of 15 months despite maximal treatment. Recent discoveries have shown that glioma cells interact with the peritumoral neuronal microenvironment, modulating tumor behavior and neuronal activity. However, the effects of tumor progression on neuronal excitability in human brain tissue are poorly understood. Here, we hypothesize that glioblastoma causes neuronal dysfunction in the human cortex by changing the electrophysiological and molecular properties of the peritumoral neuronal microenvironment in time and space. To address this hypothesis, we will investigate the electrophysiological and molecular properties of the peritumoral neuronal microenvironment using single-neuron electrophysiology, multi-array electrode recordings, and spatial transcriptomics. Furthermore, we will compare peritumoral neuronal excitability patterns in glioblastoma to non-malignant human cortex and investigate the temporospatial changes of the peritumoral neuronal microenvironment in glioma–human brain slice co-culture model by analyzing electrophysiological and molecular data at different timepoints during the tumor growth timeline. By this we aim to understand the vicious cycle in cancer neuroscience where tumor growth induces neuronal excitability and neuronal excitability induces tumor growth and move a further step towards treatment of cancer progression and tumor-related epilepsy.

• DFG Programme: Research Grants
• Major Instrumentation: MEA-System
• Instrumentation Group: 3440 Elektrophysiologische Meßsysteme (außer 300-309 und 340-343)
• Co-Investigator: Professor Dr. Dieter-Henrik Heiland