Tynninen, O. | bioRxiv Science

bioRxiv2026

A novel method for obtaining epileptic brain tissue for omic analyses using electrodes from a clinical stereoelectroencephalography study

Abstract Purpose: Developing a valid and practical method for obtaining brain tissue samples for transcriptomic and proteomic analyses using tissue adhered to stereoelectroencephalography (SEEG) electrodes, to enable investigation of the molecular mechanisms underlying chronic epilepsy. Method: Brain tissue samples adhered to SEEG electrodes were collected from six patients with drug-resistant epilepsy and preprocessed in a hospital environment after electrode removal. RNA extraction was initiated immediately, and proteomics samples were snap-frozen until subsequent analysis. The samples were categorized into three groups according to their electrophysiological profile: epileptogenic zone, propagation zone, and least-involved zone. The omic findings between these zones and anatomical brain areas were compared. Results: High-quality RNA and protein samples were obtained from tissue adhered to SEEG electrodes. Neuron- and brain-specific gene expression patterns and proteins were identified. Signs of activation of inflammatory mechanisms were most pronounced in the epileptogenic zone. Transcriptomic and proteomic findings demonstrated concordance. Conclusion: SEEG electrodes are a useful source for obtaining brain tissue for molecular characterization of chronic epilepsy. This method will enable the identification of shared and distinct molecular mechanisms in patients with varying etiologies of epilepsy.

neuroscience↗

bioRxiv2018

Vulnerability of invasive glioma cells to lysosomal membrane instabilization

Diffusive by nature, glioma challenges clinical care by the impossibility of complete surgical resection of tumor, leaving the radio- and chemoresistant cells responsible for recurrence intact. We identified mammary-derived growth inhibitor (MDGI/FABP3) as invasive glioma biomarker. Here, we show that high MDGI expression associated with poor patient survival and promoted invasive glioma cell growth both in vitro and in vivo, while MDGI silencing drastically compromised patient-derived tumoroid viability via induction of lysosomal membrane permeabilization (LMP). This alternative cell death pathway provokes release of lysosomal hydrolases into the cytosol leading inevitably to the cell death. Our results show a novel functional role for MDGI in glioma cell invasion, survival, and maintenance of the lysosomal membrane integrity as well as an unsuspected sensitivity of glioma cells to an LMP-inducing drug, anti-histamine clemastine. In a preclinical study, clemastine-treatment significantly prolonged the survival of intracranial glioblastoma-bearing animals due to eradication of invasive glioma cells. This glioma cell vulnerability to LMP-inducing drugs opens new horizons for development of novel treatments and suggest re-positioning of an established drug for new indication.

cancer biology↗