Participation of the spleen in the neuroinflammation after pilocarpine-induced status epilepticus: implications for epileptogenesis and epilepsy

Abstract

Epilepsy, a chronic neurological disorder characterized by recurrent seizures, affectsmillionsof individuals worldwide. Despite extensive research, the underlying mechanisms leading toepileptogenesis, the process by which a normal brain develops epilepsy, remain elusive.We,here, explored the immune system and spleen responses triggered by pilocarpine-inducedstatus epilepticus (SE) focusing on their role in the epileptogenesis that follows SE. Initialexamination of spleen histopathology revealed transient disorganization of white pulp, inanimals subjected to SE. This disorganization, attributed to immune activation, peaked at1-day post-SE (1DPSE) but returned to control levels at 3DPSE. Alterations in peripheralblood lymphocyte populations, demonstrated a decrease following SE, accompanied bya reduction in CD3+ T-lymphocytes. Further investigations uncovered an increased abundanceof T-lymphocytes in the piriform cortex and choroid plexus at 3DPSE, suggesting aspecific mobilization toward the Central Nervous System. Notably, splenectomy mitigatedbrain reactive astrogliosis, neuroinflammation, and macrophage infiltration post-SE, particularlyin the hippocampus and piriform cortex. Additionally, splenectomized animals exhibitedreduced lymphatic follicle size in the deep cervical lymph nodes. Most significantly, splenectomycorrelated with improved neuronal survival, substantiated by decreased neuronal lossand reduced degenerating neurons in the piriform cortex and hippocampal CA2-3 post-SE.Overall, these findings underscore the pivotal role of the spleen in orchestrating immuneresponses and neuroinflammation following pilocarpine-induced SE, implicating the peripheralimmune system as a potential therapeutic target for mitigating neuronal degenerationin epilepsy.