Internal medicine

Receptor

Pilocarpine

Status epilepticus

Epilepsy

Agonist

Neuroinflammation

Endocrinology

Psychiatry

Proinflammatory cytokine

Inflammation

Rosiglitazone

Piriform cortex

Hippocampus

Microglia

Medicine

Pharmacology

CNS Neuroscience & Therapeutics

Aims Activated microglia have been found in the forebrains and hippocampi of temporal lobe epilepsy (TLE) patients and status epileptic (SE) animal models. The peroxisome proliferator‐activated receptor γ (PPAR γ) agonist rosiglitazone has been shown to prevent microglial activation. However, its role in pilocarpine‐induced status epilepticus remains unknown. We aimed to examine the effect of the PPAR γ agonist rosiglitazone in protecting against pilocarpine‐induced status epileptic resulting from over‐activation and to explore phenotypic changes in microglia as the underlying mechanism. Methods Male C57BL/6 mice were assigned to three groups: the control group, pilocarpine‐induced (SE) group, and rosiglitazone‐treated (SE+Rosi) group. Status epileptic mice were administered 300 mg/kg pilocarpine via intraperitoneal injection. SE+Rosi mice were administered rosiglitazone (0.1 mg/kg, i.p.) after SE. Flow cytometry, immunofluorescence staining, and quantitative real‐time PCR were used to examine the activation of and phenotypic changes in microglia in the brain and to evaluate neuroinflammation. Results We found that the expression of proinflammatory CD86 and iNOS was increased and that the expression of antiinflammatory CD206 and Arg‐1 was decreased in the brains of pilocarpine‐induced SE mice compared to control mice. The mRNA levels of proinflammatory and antiinflammatory cytokines were not significantly changed in the brain. Rosiglitazone treatment significantly inhibited the proinflammatory polarization of microglia and rescued neuron loss in the temporal lobe and hippocampi of the brain after SE. Conclusion Rosiglitazone reverses microglial polarization in the brains of SE mice and also affords neuroprotection against pilocarpine‐induced status epilepticus without inducing significant changes in brain inflammation.

Rosiglitazone polarizes microglia and protects against pilocarpine‐induced status epilepticus