Abstract 7
Category: Basic Science
At the end of the session, participants will be able to:
- Characterize the spatial transcriptomic landscape of the human hippocampus
- Identify potential prognostic biomarkers of mesial temporal lobe epilepsy
- Understand the epileptogenic role of neuroinflammation
COI Disclosure:
None to disclose.
Presenter
Xuan Wang is a dedicated graduate student at Western University in London, Ontario, pursuing an M.Sc. in Pathology and Laboratory Medicine under the mentorship of Dr. Qi Zhang. With a strong foundation in medical sciences, Wang graduated with honors in Biophysics from Western University in 2023. Throughout her academic career, Wang has demonstrated a deep commitment to research, contributing significantly to multiple projects and earning accolades such as the Western Graduate Research Scholarship and the USRI Fellowship Award.
Wang’s research experience is extensive and varied, having served as a Graduate Research Assistant and Research Assistant in multiple labs at Western University. Her work includes analyzing molecular changes in mesial temporal lobe epilepsy, characterizing amygdala involvement in sudden unexpected death in epilepsy, and studying microvascular blood flow using complexity and wavelet methods. Wang has presented her findings at notable conferences and research days, and she has co-authored a publication on Laser Doppler Fluximetry in cutaneous vasculature in the Journal of Vascular Research. Her research excellence is complemented by her strong academic record, making her a promising young scientist in the field of pathology and laboratory medicine.
Authors
Xuan Wang1, Rober Abdo1, Carolyn Twible1, Chelsey Zhao1, Qi Zhang1, 2
1. Department of Pathology and Lab Medicine, Western University, London, Ontario, Canada
2. Department of Pathology and Lab Medicine, London Health Sciences Center, London, Ontario, Canada
Target Audience:
Pathologists, Residents, Medical Students
CanMEDS:
Collaborator, Scholar
Transcriptomic profiling reveals hippocampal white matter inflammation as potential epileptogenic focus in temporal lobe epilepsy
Abstract
Rationale: Hippocampal sclerosis (HS) is the most common pathological finding in surgically resected brain tissue in mesial temporal lobe epilepsy (mTLE). The histopathologic hallmark of HS is pyramidal neuronal loss within the Cornu Ammonis (CA) sectors. Twenty percent of TLE cases have no significant neuronal loss (no-HS, ILAE type 4). About 40% of no-HS patients achieve seizure freedom post-operatively.
Objectives: We performed spatial transcriptomic profiling of no-HS hippocampi to identify molecular changes associated with post-operative outcomes.
Method: Eight no-HS hippocampi were obtained from the Department of Pathology at LHSC. Five patients had Engel 1a outcome (seizure free, SF); three patients with Engel outcome 2-4 (non-seizure free, NSF). Six samples (3 SF and 3 NSF) were selected based on anatomical integrity and RNA quality. Spatial transcriptomic profiling was performed using 10x Genomics Visium technology. Data analysis was conducted using the Loupe Browser and R/Bioconductor packages to compare gene expression across various hippocampal regions.
Results: Unsupervised data-driven clustering (BayesSpace) correlates well with histology based manual annotation. Two distinct spatial domains (cluster 7 and 8) were identified in hippocampal CA1 region. Differential expression analysis identified upregulated neuroinflammation genes in the seizure free group, predominantly in the hippocampal white matter (eg. stratum radiatum). Trajectory analysis indicated disease spatial progression starting from hippocampal white matter, progressing to CA sectors, and reaching the dentate gyrus at the end.
Conclusions: Our findings suggest molecular heterogeneity of the human CA1 sector. Patient who had better post-surgical outcomes possess elevated neuroinflammatory signature in the hippocampal white matter.