Activation of the mTOR signaling pathway in peritumoral tissues can cause glioma-associated seizures

Abstract

Epileptic seizures, the most common symptom accompanying glioma, are closely associated with tumor growth and patient quality of life. However, the association between glioma and glioma-related epilepsy is poorly understood. In fact, findings related to the location of epileptogenicity have been inconsistent in previous studies. We investigated seizure foci in patients with glioma and the corresponding association between glioma-related epilepsy and the tumoral and peritumoral microenvironment. Clinical characteristics, extracellular electrophysiology, immunohistochemistry, and western blots were conducted on 12 patients with glioma; nine patients had histories of preoperative seizures while three did not. Samples from included patients were used to identify seizure foci and mTOR pathway status. Electrophysiological recordings were conducted on 36 samples (tumor, peritumoral, and normal brain tissues) from 12 patients. Interictal-like discharges (ILDs) were observed in seven of nine peritumoral tissues obtained from patients with glioma that had experienced perioperative seizures. No ILDs were observed in any other sample groups. Western blots and immunohistochemistry for mTOR pathway proteins (mTOR and S6k) suggested that the mTOR pathway was activated in peritumoral tissues of patients with seizure history, but inactivated in patients without seizure history. Our results suggest that mTOR pathway expression in peritumoral tissues is associated with tumor-related seizures, thus providing a potential target for therapeutics aimed at simultaneously controlling gliomas and seizures.

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