Microglia attenuate the kainic acid-induced death of hippocampal neurons in slice cultures

Background Status epilepticus-induced hippocampal neuronal death, astrogliosis, and the activation of microglia are common pathological changes in mesial temporal lobe epilepsy (mTLE) with resistance to antiepileptic drugs. Neuronal death in mTLE gradually progresses and is involved in the aggravation of epilepsy and the impairment of hippocampus-dependent memory. Thus, clarifying the cellular mechanisms by which neurons are protected in mTLE will significantly contribute to the treatment of epilepsy. Here, mainly using hippocampal slice cultures with or without the pharmacological depletion of microglia, we directly examined whether microglia, the resident immune cells of the brain that can act either neurotoxically or in a neuroprotective manner, accelerate or attenuate kainic acid (KA)-induced neuronal death in vitro. Methods Hippocampal slice cultures were treated with KA to induce neuronal death in vitro. Clodronate-containing liposomes or PLX3397 was used to deplete microglia in hippocampal slice cultures, and the effect on KA-induced neuronal death was immunohistochemically assessed. Results The loss of microglia significantly promoted a decrease in neuronal density in KA-treated hippocampal slice cultures. Conclusion Our results suggest that microglia are neuroprotective against KA-induced neuronal death in slice cultures.