Gene Expression Profiling of Two Epilepsy Models Reveals the ECM/Integrin signaling Pathway is Involved in Epiletogenesis

The molecular mechanisms underlying the development of epilepsy, i.e., epileptogenesis, are due to altered expression of a series of genes. Global expression profiling of temporal lobe epilepsy is confounded by a number of factors, including the variability among animal species, animal models, and tissue sampling time-points. In this study, we pooled two microarray datasets of the most used pilocarpine and kainic acid epilepsy models from the Gene Expression Omnibus database. A total of 567 known and novel genes were commonly differentially expressed across the two models. Pathway analyses demonstrated that the dysregulated genes were involved in 46 pathways. Real-time PCR and western blot analysis confirmed the activation of extracellular matrix (ECM)/integrin signaling pathways. Moreover, targeting ECM/integrin signaling inhibits astrocyte activation and promotes neuron injury in the hippocampus of epileptic mice. This study may provide a gene/pathway database that with further investigation can determine the mechanisms underlining epileptogenesis and the possible targets for neuron protection in the hippocampus after status epilepticus. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.