Metabolites of Organic Acid Pathways as Biomarkers for Epileptogenesis
Abstract number :
1.008
Submission category :
1. Basic Mechanisms / 1A. Epileptogenesis of acquired epilepsies
Year :
2022
Submission ID :
2205157
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:27 AM
Authors :
James Poe, NA – Yale School of Medicine; Mani Ratnesh Sandhu, MD – Yale School of Medicine; Roni Dhaher, PhD – Yale School of Medicine; Dennis Spencer, MD – Yale School of Medicine; Hitten Zaveri, PhD – Yale School of Medicine; Tore Eid, MD, PhD – Yale School of Medicine
Rationale: Epileptogenesis involves several alterations in cerebral metabolism, neurotransmitter systems, and neuroinflammation. Identifying changes in different metabolic pathways can help us discover new underlying mechanisms and suggest biomarkers that can be further exploited to develop anti-epileptogenic treatments. Here, we study changes in different organic acid concentrations in the epileptic focus of a transitionally relevant model of mesial temporal lobe epilepsy (MTLE).
Methods: In Sprague-Dawley rats, MSO was chronically infused into the right hippocampus to induce MTLE. PBS infused animals were used as controls. Microdialysis samples were collected in 1h aliquots from the epileptic or control hippocampus for up to 7 days. Using liquid chromatography-tandem mass spectrometry, more than 20 organic acids were quantified in the microdialysis samples. The student’s t-test was used to compare concentrations between the epileptic (MSO) and control (PBS) groups.
Results: We observed several organic acids with a significant change in concentration between epileptic and control hippocampus. There was significant increase in lactic acid (P< 0.001), p-hydroxy-phenyl lactic acid (P = 0.023) and alpha-hydroxy butyric acid (P = 0.03) concentration in epileptic focus. Whereas homovanillic acid (P = 0.04), hippuric acid (P = 0.001), n-acetyl-aspartic acid (P< 0.001) had significant decrease in concentration in epileptic focus as compared to control._x000D_
Basic Mechanisms