# Temporal lobe epilepsy is associated with neuroinflammation, extracellular matrix remodeling, and synaptic protein alterations

## TL;DR

This study finds that temporal lobe epilepsy involves inflammation and changes in brain tissue structure, particularly in the hippocampus, which may lead to seizures.

## Contribution

The study identifies region-specific molecular changes in the hippocampus linked to neuroinflammation and synaptic dysfunction in temporal lobe epilepsy.

## Key findings

- Hippocampal TLE tissue shows upregulation of proteins related to inflammation and extracellular matrix remodeling.
- Synaptic proteins like glutamate and GABA receptors are downregulated in the hippocampus but preserved or increased in neocortical and white matter regions.
- The findings suggest that hippocampal inflammation contributes to epileptogenesis, while other brain regions may compensate.

## Abstract

Temporal lobe epilepsy is the most prevalent form of drug-resistant focal epilepsy and is frequently associated with neuronal cell loss and astrogliosis in the hippocampus, i.e. hippocampal sclerosis (HS).

In this study, we performed mass spectrometry-based proteomic profiling of microdissected hippocampal, neocortical, and white matter tissue obtained from TLE patients and respective control samples.

In hippocampal TLE tissue, we observed significant upregulation of proteins involved in complement system activation, extracellular matrix (ECM) organization, and astrocyte reactivity, indicative of active inflammatory remodeling within the sclerotic hippocampus. Conversely, synaptic proteins, including glutamate and gamma-aminobutyric acid (GABA) receptors, along with other regulators of synaptic structure and function, were markedly downregulated. Interestingly, in neocortical and white matter regions from the same TLE patients, immune- and ECM-related proteins were downregulated or unchanged, whereas synaptic proteins were preserved or upregulated.

These region-specific molecular signatures suggest that inflammatory-driven ECM remodeling is spatially restricted to the epileptogenic hippocampus, where it may contribute to synaptic destabilization and network dysfunction. Together, our findings support the hypothesis that inflammatory ECM remodeling in the hippocampus plays a central role in epileptogenesis in TLE. In contrast, the neocortical and white matter regions may undergo compensatory adaptions. The convergence of immune and ECM-related alterations on synaptic structures highlights a potential pathophysiological axis in epilepsy and points to novel molecular targets for therapeutic intervention.