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.