Surreal illustration of an epileptic brain highlighting areas of high and low electrical activity, symbolizing proteomic changes.

Unlocking Epilepsy: How Brain Tissue Analysis is Paving the Way for New Treatments

Elliot Brynn in Health & Wellness June 2025 • 4 min read.

"Proteomic analysis of epileptic neocortex reveals potential targets for managing seizures and improving patient outcomes."

Epilepsy, a neurological disorder affecting millions worldwide, remains a significant challenge for both patients and medical professionals. Characterized by recurrent seizures, epilepsy's underlying molecular mechanisms are still not fully understood, making effective treatment elusive for many.

For those who don't respond to medication, surgical removal of brain regions that trigger seizures can offer relief. This procedure provides an invaluable opportunity to study human brain tissue and understand the cellular and molecular basis of epilepsy. A recent study delved into this area, seeking to identify common proteomic patterns in brain regions responsible for generating epileptic discharges.

This article explores the findings of this proteomic study, which analyzed neocortical tissue from six patients with refractory epilepsy. The research aimed to uncover how protein expression differs between regions that produce epileptic discharges and those that do not, offering new insights into potential therapeutic targets.

Decoding the Epileptic Brain: A Proteomic Approach

Surreal illustration of an epileptic brain highlighting areas of high and low electrical activity, symbolizing proteomic changes.

The research team conducted a detailed proteomic analysis as part of the Systems Biology of Epilepsy Project (SBEP). They studied in vivo electrophysiologically characterized human brain samples taken from patients undergoing surgery for refractory epilepsy. The study's unique design involved comparing protein expression within the same patient—contrasting highly epileptic regions with less epileptic ones.

To quantify epileptic activity, researchers measured the frequency of interictal spikes (electrical activity between seizures). Proteins were extracted from three subcellular fractions and analyzed using 2D differential gel electrophoresis (2D-DIGE). This technique revealed 31 protein spots that showed significant changes in expression.

Interictal Spikes: Electrical activity between seizures, serving as a key indicator.
2D-DIGE Analysis: Identifying 31 protein spots with notable expression changes.
GFAP Findings: Glial fibrillary acidic protein consistently downregulated in high-spiking brain tissue.

One notable finding was the consistent downregulation of glial fibrillary acidic protein (GFAP) in brain tissue with high spiking activity, which showed a strong negative correlation with spike frequency. GFAP is crucial for astrocyte structure and function, suggesting that glial cell activity may be reduced in epileptic regions. The researchers also developed a two-step method to pinpoint protein species that changed frequently across patients, identifying 397 protein spots of interest (SOI). These SOIs were clustered based on protein expression patterns to identify potential markers and predict proteomic changes tied to histological differences and molecular pathways.

Implications and Future Directions

This study’s innovative approach, combined with proteomic data analysis, predicts new glial changes, increased angiogenesis, and alterations in cytoskeleton and neuronal projections in regions with high interictal spiking. Validating these findings through quantitative histological staining of the same tissues confirmed vascular and glial changes, providing new insights into neocortical epilepsy's structural and functional underpinnings. These discoveries open new avenues for targeted treatments and interventions, offering hope for more effective management of this complex neurological disorder.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1371/journal.pone.0195639, Alternate LINK

Title: Proteomic Analysis Of Human Epileptic Neocortex Predicts Vascular And Glial Changes In Epileptic Regions

Subject: Multidisciplinary

Journal: PLOS ONE

Publisher: Public Library of Science (PLoS)

Authors: Gal Keren-Aviram, Fabien Dachet, Shruti Bagla, Karina Balan, Jeffrey A. Loeb, Edward A. Dratz

Published: 2018-04-10

Everything You Need To Know

What is the primary goal of the proteomic analysis in understanding epilepsy?

The primary goal of the proteomic analysis is to identify differences in protein expression between brain regions that generate epileptic discharges and those that do not. This comparison aims to uncover potential therapeutic targets for more effective treatment of epilepsy by understanding the cellular and molecular basis of the disorder. The study focused on neocortical tissue from patients with refractory epilepsy.

How did the study analyze protein expression in the brain tissue samples?

The study utilized a detailed proteomic analysis as part of the Systems Biology of Epilepsy Project (SBEP). Researchers used 2D differential gel electrophoresis (2D-DIGE) to analyze proteins extracted from three subcellular fractions of the brain tissue. This technique allowed the identification of 31 protein spots showing significant changes in expression. Furthermore, a two-step method was developed to pinpoint 397 protein spots of interest (SOI), which were then clustered based on expression patterns.

What role does GFAP play in the context of epilepsy, and what did the study find regarding its expression?

Glial fibrillary acidic protein (GFAP) is crucial for astrocyte structure and function. The study found that GFAP was consistently downregulated in brain tissue with high interictal spiking activity, showing a strong negative correlation with spike frequency. This suggests that glial cell activity may be reduced in the regions responsible for epileptic activity, potentially impacting the brain's overall functionality and contributing to the generation of seizures.

What are interictal spikes, and why are they significant in the study?

Interictal spikes are electrical activities that occur between seizures. In the study, the frequency of these spikes was measured to quantify epileptic activity. The analysis of interictal spikes served as a key indicator of the level of epileptic activity in different brain regions. Comparing the expression patterns with the spiking frequency provided valuable insights into the relationship between protein expression and the occurrence of seizures. The study used the frequency of interictal spikes to characterize and compare regions of the brain.

What are the potential implications of the study's findings, and what future directions might be explored?

The study's findings suggest new glial changes, increased angiogenesis, and alterations in cytoskeleton and neuronal projections in areas with high interictal spiking. These discoveries open avenues for targeted treatments and interventions, offering hope for more effective management of epilepsy. Future research could validate the findings through quantitative histological staining of the same tissues. Further exploration might involve targeting specific proteins identified as potential therapeutic targets. The validation of these findings could lead to the development of more effective treatments and interventions.