RNA sequencing analysis of cortex and hippocampus in a kainic acid rat model of temporal lobe epilepsy to identify mechanisms and therapeutic targets related to inflammation, immunity and cognition.

Temporal lobe epilepsy (TLE) is the most common type of refractory epilepsy, in which inflammation is suggested to cause abnormal neuronal connections and neural networks. However, the expression of inflammatory genes in epilepsy remains incomplete, particularly in the context of the cortex, which is a hub of epileptic transmission but also is essential for mediating sensory, motor and cognitive function. Here, a rat model of epilepsy was established by kainic acid (KA) administration Gene transcriptome was explored in 4 signature phases in the hippocampus and cortex: acute damage (3 h), onset of epileptogenesis (3 d), spontaneous epilepsy (2 w) and cognitive impairment (9 w). Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis was applied to unravel the significantly altered pathways. We found, in both the hippocampus and cortex, the inflammatory gene was up-regulated in the acute phase, followed by a gradual decline; the phagocytosis and glial activation were remarkably increased since day 3; persistently down-regulated synaptic transmission and neuronal development started from the 3 h phase and lasted through the 9 w phase. While, the changed gene expression in the cortex fall into the same categories but were relatively lagging behind that in the hippocampus, also showing less number and distinct genes. Collectively, this study demonstrated the changes of gene transcriptome in the cortex and hippocampus in the signature phases after the KA administration, illustrating the association between epileptogenesis, inflammation genes and cognitive dysfunction, and may benefit identifying novel therapeutic targets for treating TLE and its comorbidities.