The expression of keratan sulfate reveals a unique subset of microglia in the mouse hippocampus after pilocarpine-induced status epileptics

Induction of keratan sulfate in microglia has been found in several animal models of neurological disorders. However, the significance of keratan sulfate-expressing microglia is not fully understood. To address this issue, we analyzed the characteristics of microglia labeled by the 5D4 epitope, a marker of high-sulfated keratan sulfate, in the mouse hippocampus during the latent period after pilocarpine-induced status epilepticus (SE). Only 5D4-negative (5D4⁻) microglia were found in the CA1 region of vehicle-treated controls and pilocarpine-treated mice at 1 day after SE onset. A few 5D4⁺ microglia appeared in the strata oriens and radiatum at 5 days post-SE, and they were distributed into the stratum pyramidale at 14 days post-SE. The expressions of genes related to both anti- and pro-inflammatory cytokines were higher in 5D4⁺ cells than in 5D4⁻ cells at 5 but not 14 days post-SE. The expressions of genes related to phagocytosis were higher in 5D4⁺ cells than in 5D4⁻ cells throughout the latent period. The phagocytic activity of microglia, as measured by engulfment of the zymosan bioparticles, was higher in 5D4⁺ cells than in 5D4⁻ cells. The contact ratios between excitatory synaptic boutons and microglia were also higher in 5D4⁺ cells than in 5D4⁻ cells at 5 and 14 days post-SE. The excitatory/inhibitory ratios of synaptic boutons within the microglial domain were lower in 5D4⁺ cells than in 5D4⁻ cells at 14 days post-SE. Our findings indicate that 5D4⁺ microglia may play some role in epileptogenesis via pruning of excitatory synapses during the latent period after SE.