Depletion Of Microglia Exacerbates Seizures And Hippocampal Neuronal Death In Mouse Model Of Epilepsy

Epilepsy is one of the most common chronic neurological diseases,characterized by recurrent seizures caused by abnormal synchronized discharge of a large number of neurons in the brain.There are about 2 million patients with temporal lobe epilepsy in china,whose symptoms are often not well treated with antiepileptic drugs or surgical resection.Epileptic seizure is characterized by unpredictability,recurrence and self-limitation.Pathological changes in epilepsy include loss of neurons,gliosis,and neuroinflammation.Microglia,are macrophages and immune cells in the central nervous system,Activated microglia have complex phenotypes that may have different effects on brain function,depending on the stage of the seizure.Microglia are known to mediate inflammatory reaction,phagocytosis,and synaptic pruning in the epileptic brain.However,it is unknown how the existence and activation of microglia may exert an action in modulating epileptic seizures and neuronal survival of mice changed with convulsants.In this paper,we investigated the role of microglia in acute seizures by removing microglia from the brain by pharmacologic methods.We treated ICR mice with CSF1R inhibitor PLX3397 for 21 consecutive days,and then induced seizures by drugs.We found that in the acute epilepsy model induced by pilocarpine,microglia depletion increased susceptibility to epilepsy,significantly increased severity of epilepsy,and increased neuronal damage in the DG region of the hippocampus,compared with the control group.In the pentylenetetrazol-induced acute epilepsy model,the seizure severity and network excitability were significantly increased in mice with microglia depletion.Combined with the above results,we found that residual microglia have a protective effect against seizures,suggesting that microglia may be a potential target for epileptic drug therapy.