Cervical spinal cord stimulation exerts anti-epileptic effects in a rat model of status epilepticus through the suppression of CCL2-mediated cascades

Abstract Objective Epidural spinal cord stimulation (SCS) is indicated for the treatment of intractable pain and is widely used in clinical practice. In previous basic research, the therapeutic effects of SCS have been demonstrated for epileptic seizure. However, the mechanism has not yet been elucidated. In this study, we investigated the therapeutic effect of SCS and the mechanism of epileptic seizure. Methods First, SCS in the cervical spine was performed. The rats were divided into four groups: control group and treatment groups with SCS conducted at 2, 5, and 300 Hz frequency. Two days later, convulsions were induced by the intraperitoneal administration of kainic acid, followed by video monitoring to assess seizures. We also evaluated glial cells in the hippocampus by fluorescent immunostaining, electroencephalogram measurements, and inflammatory cytokines such as C-C motif chemokine ligand 2 (CCL2) by quantitative real-time polymerase chain reaction. Results Seizure frequency and the number of glial cells were significantly lower in the 300 Hz group than in the control group. SCS at 300 Hz decreased gene expression level of CCL2, which induces monocyte migration. Conclusion SCS has anti-seizure effects by inhibiting CCL2-mediated cascades. CCL2 and glial cells may be involved in the mechanism of status epilepticus.