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The histoarchitectonic glycosylation pattern of diffused and perineuronal condensed extracellular matrix in hippocampal sclerosis

Introduction: Hippocampal sclerosis (HS) is the commonest histopathological finding in patients with drug-resistant mesial temporal lobe epilepsy (MTLE). The type 1 HS (ILAE type 1), with severe pyramidal neurons (PyN) loss in CA1 and CA4 regions as hallmark, and parvalbumin interneurons number and connectivity, depletion is most fre quent. Currently, extracellular matrix (ECM) is recognized as an important regulator of excitability and synaptic plasticity, especially its condensed peri-cellular form, perineuronal nets (PNN). The different ECM components and PNN are suspected to have role in epileptogenesis in experimental rodent models. Aim and methods: Aim of this retrospective study is to reveal the significance of PNN and other characteristics of ECM by correlating them to cellular (NeuN, GFAP, PV), molecular (WFA), histoarchitectonical and clinical findings from 65 patents surgically treated due to pharmacoresistant MTLE caused by HS. Results: In addition to previously shown features of HS1, as reduced number and impoverish morphology of Py and PV neurons, we found significant negative correlation of PV-neurons in CA4 and GD with number of antiepileptic drugs used at the same time during period of one year before surgery. We also found a change in the distribution of the specific glycosylation pattern recognized by WFA, presented as partially degraded PNNs, but concomitantly highly WFA positive glycan component of the dispersed ECM in CA4. The PNN are reduced around pyramidal neurons in all regions (CA4-CA1) as well as around PV-immunoreactive interneurons. Conclusion: PNN reduction and change of the glycosylation profile of the neuropil in the HS1-MTLE possibly contribute to the pathophysiology of drug-resistant epilepsy, and might be possible ground for novel therapies.

MTLE ; perineuronal nets ; drug-resistant epilepsy

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