ArticleMolecular and cellular neurosciences2026
Severity-dependent proteomic alterations in the rat hippocampus following pilocarpine-induced status epilepticus.
Article in Molecular and cellular neurosciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Status epilepticus (SE) is a prolonged seizure state that can induce lasting hippocampal damage and promote the development of spontaneous seizures and cognitive deficits. The severity and duration of SE affect long-term outcomes; however, many studies rely on behavioral assessments such as the Racine scale, which may miss subclinical or non-convulsive seizures and leave the molecular effects of mild SE unclear. Here, we examined whether behavioral seizure severity in the pilocarpine rat model of acquired epilepsy correlates with distinct hippocampal proteomic changes. Adult male rats were classified as control, mild SE, or severe SE following pilocarpine-induced seizures, and hippocampal tissue was analyzed using mass spectrometry-based proteomics. Partial least squares discriminant analysis revealed distinct proteomic signatures across groups. Severe SE was associated with widespread changes (129 differentially expressed proteins [DEPs]) involving synaptic structure, RNA regulation, and metabolism, whereas mild SE showed fewer alterations (81 DEPs) related primarily to synaptic organization and endocytosis. Comparison of severe and mild SE identified 76 DEPs enriched in pathways linked to synaptic plasticity and neurodegeneration, with 23 proteins exhibiting a stepwise expression pattern across seizure severities. Glial and inflammatory proteins emerged as candidate markers of seizure burden. These findings demonstrate that behavioral seizure severity aligns with specific hippocampal proteomic profiles and that even lower-severity SE induces molecular changes relevant to epileptogenic progression.
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