Rosiglitazone polarizes microglia and protects against pilocarpine-induced status epilepticus

Jing Peng1, Kan Wang1, Weiwei Xiang1

  • 1Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Abstract

Insights

Rosiglitazone, a PPAR γ agonist, reversed harmful microglial polarization in mice with status epilepticus (SE). This treatment protected neurons in the temporal lobe and hippocampi, offering neuroprotection against SE.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Activated microglia are implicated in temporal lobe epilepsy (TLE) and status epilepticus (SE).
  • Peroxisome proliferator-activated receptor γ (PPAR γ) agonists, like rosiglitazone, can inhibit microglial activation.
  • The effect of rosiglitazone on pilocarpine-induced SE is not well understood.

Purpose of the Study:

  • To investigate the neuroprotective effects of rosiglitazone in a pilocarpine-induced SE model.
  • To explore the underlying mechanism involving microglial phenotypic changes.

Main Methods:

  • Mice were divided into control, SE, and SE+rosiglitazone groups.
  • SE was induced using pilocarpine (300 mg/kg, i.p.).
  • Rosiglitazone (0.1 mg/kg, i.p.) was administered to the SE+Rosi group.
  • Microglial activation, phenotype, and neuroinflammation were assessed using flow cytometry, immunofluorescence, and qPCR.

Main Results:

  • SE mice showed increased proinflammatory markers (CD86, iNOS) and decreased anti-inflammatory markers (CD206, Arg-1) in the brain.
  • Rosiglitazone treatment inhibited proinflammatory microglial polarization.
  • Rosiglitazone treatment rescued neuron loss in the temporal lobe and hippocampi.

Conclusions:

  • Rosiglitazone effectively reverses microglial polarization in SE mouse brains.
  • This agent provides neuroprotection against pilocarpine-induced SE.
  • Neuroprotection occurs without significant alteration of overall brain inflammation.

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