Spatial Changes in Hippocampal Transcriptomic Profiles Following Limbic Non-convulsive Status Epilepticus: Insights...

The long-term effects of non-convulsive status epilepticus (NCSE) and their mechanisms in the brain remain largely unknown. Such insight is needed to better shape the clinical approach to this condition. Here, we investigated long-term alterations in hippocampal transcriptomic profiles following an episode of limbic NCSE in periadolescent rats. Cortical and hippocampal mRNA expressions were measured 2 months following intrahippocampal kainic acid (NCSE group, n = 3) or saline injections (controls, n = 4). Compared to controls, NCSE-treated rodents exhibited a significant twofold downregulation in 126 genes in the CA1 hippocampal subfield, 11 in the CA2-3 region, and 21 in the dentate/hilar areas. Most of the identified genes are known to play an essential role in learning and hippocampal plasticity. Additional roles include modulation of inflammatory responses. Twenty altered genes are known to contribute to human intellectual and mental disease pathology, and nine out of these are direct causes of cognitive and neurodevelopmental brain disorders. Spatial deconvolution analyses revealed NCSE-related increases in CA2-3 microglia and hilar astrocytes coupled with increases in dentate GABAergic neurons. These long-term region-specific cellular and molecular hippocampal alterations may contribute to both inflammatory states and disturbances in neuronal function. Taken together, these gene expression changes are suggestive of neuroinflammation-driven synaptic dysfunction following NCSE.