Characterizing Hippocampal Dentate Gyrus Involvement in Temporal Lobe Epilepsy
Abstract number :
2.386
Submission category :
14. Neuropathology of Epilepsy
Year :
2023
Submission ID :
1149
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Carolyn Twible, BSc – Western University
Qi Zhang, MD, PhD – London Health Sciences Center, Western University
Rationale: Hippocampal sclerosis (HS) is the most common pathology finding for drug-resistant temporal lobe epilepsy (TLE). HS is diagnosed by identifying pyramidal neuronal loss and gliosis in Cornu Ammonis (CA). Dentate gyrus (DG) is the critical entry point in to the hippocampus and possesses the unique function of adult neurogenesis. However, changes in DG are not emphasized in the current diagnostic criteria of HS. In this study, we will characterize the morphological and genomic features of the hippocampal DG in TLE patients and investigate the underlying epileptogenic mechanisms.
Methods: Twenty-one TLE surgical resection cases (14 HS, 7 no-HS) and 10 control cases (4 non-TLE epilepsy control, 6 non-epilepsy control) were included. QuPath software was used to perform morphometry analysis on the DG, including Delaunay mean, cellular density, nuclear size and circularity. The DG of 18 selected TLE cases were micro dissected and underwent gene expression profiling, using NanoString targeted panels (1400 genes, targeted Neuroinflammation and Glial Profiling panels). Histopathological diagnosis and post-operative outcome were included for clinicopathological correlation.
Results: 1) HS patients show a significant increase in granule cell (GC) spacing and decrease in GC density within the DG compared to no-HS patients. 2) Regardless of the clinical diagnosis, patients that achieved seizure freedom post-operatively (Engel outcome scale 1a) demonstrated an increase in GC spacing and decrease in GC density in comparison to patients without significant seizure reduction. 3) The DG of HS patients demonstrated significant complement system activation, increased gliosis (both A1 & A2 astrocytes), matrix remodelling, and apoptosis but a decrease in neurogenesis, GABAergic and glutametergic synapses, and neuronal populations.
Conclusions: Dentate gyrus has distinct morphometric features and gene expression in TLE patients, suggesting an important role in epileptogenesis.
Funding: EpLink, Lawson Internal Research Fund Studentship
Neuropathology of Epilepsy