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Updated: Apr 6, 2026
Lipidomics and Transcriptomics in Neurological Diseases
Published on: March 18, 2022
Interleukin-18 expression increases in response to neurovascular damage following soman-induced status epilepticus in
Erik A Johnson1, Michelle A Guignet1, Thuy L Dao1
1Research Division, Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense (USAMRICD), Aberdeen Proving Ground, MD 21010-5400 USA.
Background:
Status epilepticus (SE) can cause neuronal cell death and impaired behavioral function. Acute exposure to potent acetylcholinesterase inhibitors such as soman (GD) can cause prolonged SE activity, micro-hemorrhage and cell death in the hippocampus, thalamus and piriform cortex. Neuroinflammation is a prominent feature of brain injury with upregulation of multiple pro-inflammatory cytokines including those of the IL-1 family. The highly pleiotropic pro-inflammatory cytokine interleukin-18 (IL-18) belongs to the IL-1 family of cytokines and can propagate neuroinflammation by promoting immune cell infiltration, leukocyte and lymphocyte activation, and angiogenesis and helps facilitate the transition from the innate to the adaptive immune response. The purpose of this study is to characterize the regional and temporal expression of IL -18 and related factors in the brain following SE in a rat GD seizure model followed by localization of IL-18 to specific cell types.
Methods:
The protein levels of IL-18, vascular endothelial growth factor and interferon gamma was quantified in the lysates of injured brain regions up to 72 h following GD-induced SE onset using bead multiplex immunoassays. IL-18 was localized to various cell types using immunohistochemistry and transmission electron microscopy. In addition, macrophage appearance scoring and T-cell quantification was determined using immunohistochemistry. Micro-hemorrhages were identified using hematoxylin and eosin staining of brain sections.
Results:
Significant increases in IL-18 occurred in the piriform cortex, hippocampus and thalamus following SE. IL-18 was primarily expressed by endothelial cells and astrocytes associated with the damaged neurovascular unit. The increase in IL-18 was not related to macrophage accumulation, neutrophil infiltration or T-cell appearance in the injured tissue.
Conclusions:
These data show that IL-18 is significantly upregulated following GD-induced SE and localized primarily to endothelial cells in damaged brain vasculature. IL-18 upregulation occurred following leukocyte/lymphocyte infiltration and in the absence of other IL-18-related cytokines, suggesting another function, potentially for angiogenesis related to GD-induced micro-hemorrhage formation. Further studies at more chronic time points may help to elucidate this function.
