Clec7a promotes hippocampal microglial activation in rats with status epilepticus via inducing the TLR4/MyD88/NF-κB signaling pathway

Microglial polarization imbalance between pro-inflammatory M1 and anti-inflammatory M2 phenotypes is a key mechanism in epilepsy-related neuroinflammation. This study explores the role of C-type lectin domain containing 7A (Clec7a) in M1 microglial polarization in epilepsy. An AAV-shClec7a was injected intra-hippocampally into Sprague-Dawley rats prior to induction of status epilepticus (SE) using lithium-pilocarpine. CLEC7A expression was assessed via qRT-PCR and Western blot. Histopathology was evaluated using H&E and Nissl staining. M1 markers and cytokines were analyzed by qRT-PCR/Western blot. The effects of Clec7a silencing were examined in kainic acid-stimulated BV2 cells and primary microglia. CLEC7A was significantly upregulated in epileptic models. AAV-shClec7a reduced Racine score, seizure frequency and duration, alleviated hippocampal damage, and suppressed M1 polarization and neuroinflammation, evidenced by decreased IBA1, iNOS, IL-1β, IL-6, and TNF-α, and increased IL-10 levels. Silencing Clec7a in vitro also inhibited M1 polarization and inflammation, and suppressed TLR4/MyD88/NF-κB pathway activation. Overexpression of Nfkb reversed the inhibition of M1 polarization induced by Clec7a silencing. Meanwhile, TLR4 Inhibitor TAK-242 reversed Clec7a-induced M1 polarization. Clec7a is upregulated in epilepsy and promotes M1 polarization and neuroinflammation, mediated at least partially through the TLR4/MyD88/NF-κB signaling pathway.