Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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Effect of Pioglitazone on Perihematomal Edema in Intracerebral Hemorrhage Mouse Model by Regulating NLRP3 Expression and Energy Metabolism

  • Kim, Hoon (Department of Neurosurgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Lee, Jung Eun (Department of Neurosurgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Yoo, Hyun Ju (Biomedical Research Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Sung, Jae Hoon (Department of Neurosurgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Yang, Seung Ho (Department of Neurosurgery, Cell Death Disease Research Center, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea)
  • Received : 2020.02.27
  • Accepted : 2020.05.26
  • Published : 2020.11.01
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Abstract

Objective : Cerebral edema is the predominant mechanism of secondary inflammation after intracerebral hemorrhage (ICH). Pioglitazone, peroxisome proliferator-activated receptor gamma agonist has been shown to play a role in regulation of central nervous system inflammation. Here, we examined the pharmacological effects of pioglitazone in an ICH mouse model and investigated its regulation on NLRP3 inflammasome and glucose metabolism. Methods : The ICH model was established in C57 BL/6 mice by the stereotactical inoculation of blood (30 µL) into the right frontal lobe. The treatment group was administered i.p. pioglitazone (20 mg/kg) for 1, 3, and 6 days. The control group was administered i.p. phosphate-buffered saline for 1, 3, and 6 days. We investigated brain water contents, NLRP3 expression, and changes in the metabolites in the ICH model using liquid chromatography-tandem mass spectrometry. Results : On day 3, brain edema in the mice treated with pioglitazone was decreased more than that in the control group. Expression levels of NLRP3 in the ICH model treated with pioglitazone were decreased more than those of the control mice on days 3 and 7. The pioglitazone group showed higher levels of glycolytic metabolites than those in the ICH mice. Lactate production was increased in the ICH mice treated with pioglitazone. Conclusion : Our results demonstrated less brain swelling following ICH in mice treated with pioglitazone. Pioglitazone decreased NLRP3-related brain edema and increased anaerobic glycolysis, resulting in the production of lactate in the ICH mice model. NLRP3 might be a therapeutic target for ICH recovery.

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References

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