engleski

Extracellular matrix profile in hippocampal sclerosis

Hippocampal sclerosis (HS) is the commonest histopathological finding in patients with drug- resistant mesial temporal lobe epilepsy (MTLE). The type 1 HS is the most prevalent type characterized by severe loss of pyramidal neurons, parvalbumin (PV) interneurons, and gliosis in the CA1 and CA4 fields. The extracellular matrix (ECM) is recognized as an important regulator of excitability and synaptic plasticity, especially in its highly condensed pericellular form of perineuronal nets (PNN). As experimental rodent models suggest that the different ECM components and PNN may have a role in epileptogenesis this study aimed to analyze and correlate PNN, glycosylation pattern with Wisteria floribunda agglutinin (WFA) and other ECM constituents, and expression of Nuclear-neuronal marker (NeuN), and parvalbumin (PV), with clinical findings of 65 patients surgically treated for pharmacoresistant MTLE caused by HS. Apart from the reduced number and impoverished morphology of pyramidal neurons and PV interneurons in HS, we found a changed distribution of the specific glycosylation pattern recognized by WFA. The proteoglycans, versican, and aggrecan show significantly changed expression patterns, whereas other ECM constituents as fibronectin, chondroitin-sulfate proteoglycan-56, and neurocan were slightly altered or showed no apparent difference. We also found reduced WFA specific glycosylation of the PNN around pyramidal neurons in all CA fields (CA4-CA1) as well as around PV-immunoreactive interneurons and simultaneously increased WFA specific glycosylation of the diffuse ECM in all CA fields. These findings suggest that PNN reduction and change of the glycosylation neuropil profile in the MTLE due to HS may cause the increase of the excitability of pyramidal hippocampal neurons, thus contributing to the development of drug- resistant epilepsy, at the same time offering a potential therapeutic target.

human hippocampus ; drug-resistant epilepsy ; perineuronal nets ; aggrecan

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