期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 15, 页码 -出版社
MDPI
DOI: 10.3390/ijms23158197
关键词
human hippocampus; drug-resistant epilepsy; perineuronal nets; aggrecan
资金
- Croatian Science Foundation [IP-2019-04-3182, DOK-2018-013771, IP-2019-04-3584]
- Scientific Centre of Excellence for Basic, Clinical, and Translational Neuroscience CoRE-NEURO (European Union through the European Regional Development Fund) [GA KK01.1.1.01.0007]
- University of Zagreb [10106-22-3116]
This study evaluated the ECM profile of HS1 in drug-resistant MTLE patients and found changes in PNNs, ECM proteins, and glycosylation patterns associated with the condition. These findings suggest that ECM molecules and their modulators could be potential targets for developing new therapeutic approaches to drug-resistant epilepsy.
The extracellular matrix (ECM) is an important regulator of excitability and synaptic plasticity, especially in its highly condensed form, the perineuronal nets (PNN). In patients with drug-resistant mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis type 1 (HS1) is the most common histopathological finding. This study aimed to evaluate the ECM profile of HS1 in surgically treated drug-resistant patients with MTLE in correlation to clinical findings. Hippocampal sections were immunohistochemically stained for aggrecan, neurocan, versican, chondroitin-sulfate (CS56), fibronectin, Wisteria floribunda agglutinin (WFA), a nuclear neuronal marker (NeuN), parvalbumin (PV), and glial-fibrillary-acidic-protein (GFAP). In HS1, besides the reduced number of neurons and astrogliosis, we found a significantly changed expression pattern of versican, neurocan, aggrecan, WFA-specific glycosylation, and a reduced number of PNNs. Patients with a lower number of epileptic episodes had a less intense diffuse WFA staining in Cornu Ammonis (CA) fields. Our findings suggest that PNN reduction, changed ECM protein, and glycosylation expression pattern in HS1 might be involved in the pathogenesis and persistence of drug-resistant MTLE by contributing to the increase of CA pyramidal neurons' excitability. This research corroborates the validity of ECM molecules and their modulators as a potential target for the development of new therapeutic approaches to drug-resistant epilepsy.
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