Predicting epilepsy with peripheral blood transcriptome biomarkers during early latent period

Abstract

Status epilepticus (SE) is a common cause of hippocampal neurodegeneration and synaptic reorganization that may or may not lead to the development of epilepsy. Currently there is no method to predict whether chronic epilepsy would develop in post‐SE patients. We used microarrays to analyze expression changes in the blood of two rat models of chronic epilepsy to identify prognostic peripheral biomarkers of epilepsy.Peripheral blood was collected from Adult Wistar male rats before SE and one, three, seven and thirty days after subjected to SE induced by either systemic pilocarpine or intrahippocampal kainic acid. Blood RNA was used for global transcriptome analysis using microarrays. Post‐SE animals underwent continuous monitoring to retrospectively correlate seizure syndrome with the changes in blood transcriptome profile.We identified nearly 100 predictor/biomarker genes for later occurring chronic seizures regulated similarly in both models, which were confirmed in independent groups of post‐SE rats by semi quantitative RT‐PCR and by a custom designed prognostic microarray.The molecular signature preceding the development of epilepsy present in the peripheral blood allows the design of a prognostic/diagnostic transcriptome biomarker chip for potential epilepsy patients and monitoring the effectiveness of antiepileptogenic therapy.This work was supported by NIH Grant NS060476‐01 (SLK).