Abstracts

Lipopolysaccharide (LPS) conditioning is a phenomenon whereby LPS selectively activates anti-inflammatory mediators in a structure and/or dose-dependent manner. Our previous studies (PMID: 33893636, #3.006 in AES 2024) established that when induced shortly after lateral fluid percussion injury (LFPI) in the rat, LPS conditioning might counteract post-traumatic epileptogenesis. Furthermore, LPS derived from Akkermansia Municiphila (AM-LPS) was more effective than the one derived from Escherichia Coli (EC-LPS) (#3.006 in AES 2024). One of the identified potential mediators of the protective effects of LPS in post-traumatic epilepsy (PTE) was Triggering Receptor Expressed on Myeloid cells 2 (TREM2)- an IgG expressed predominantly in microglial cells, responsible for the clearance of debris after neuronal injury and stress. In this study, we further examined the expression of TREM2 after LFPI and its modulation by AM-LPS and EC-LPS. 

Ten-week-old Sprague-Dawley rats were subjected to moderate to severe TBI using the lateral fluid percussion injury model (LFPI) or SHAM. One hour after TBI, subcutaneous osmotic pumps were implanted (1 week) according to the assigned group: LPS (100 µg/kg/day) from Escherichia coli (EC-LPS) or Akkermansia (AM-LPS), or vehicle (saline). At 7 days post-TBI, 5-7 rats per group were perfused, brains were frozen, and coronal 30um brain sections were stained with immunochemistry specific for TREM2.  Signal densitometry was done blinded to group and side and the average cellular signal intensity for TREM2-immunoreactivity (TREM2-ir) at cortical, hippocampal or thalamic regions at the level of the anterodorsal hippocampus. Linear mixed model analysis considering repeated measures was performed. Double immunofluorescent staining was done using anti-TREM2 antibody and either of mouse NeuN, Iba1, GFAP. Statistical significance was set at p< 0.05.