PPARgamma agonist pioglitazone reduces [corrected] neuronal cell damage after transient global cerebral ischemia through matrix metalloproteinase inhibition

The European Journal of Neuroscience
Kyung-Jae LeeSeong-Ryong Lee

Abstract

Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, inhibits ischemia-induced injury in various tissues including neural tissue. Pioglitazone has also been shown to reduce matrix metalloproteinase (MMP) activity. Because MMP is known to play a major role in the pathophysiology of brain ischemia, the present study was undertaken to test whether pioglitazone attenuates ischemic neuronal damage through MMP inhibition. C57BL/6 mice were subjected to global brain ischemia for 20 min. Animals were killed 72 h after ischemia. Oral pioglitazone (40 mg/kg/day, as a suspension in 0.5% carboxymethylcellulose) was administered to mice twice daily for 3 days before ischemia and twice daily after ischemia until the animals were killed. We investigated gelatinase activity by zymography and laminin immunohistochemistry. Histological analysis was also performed to test the protective effect of pioglitazone on neuronal damage. Mice treated with pioglitazone had attenuated gelatinase activity. Gelatin gel and in situ zymography showed up-regulation of gelatinase activity after ischemia. Pioglitazone significantly inhibited ischemia-induced elevation of the active form of MM...Continue Reading

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Citations

Jan 6, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Ke-Jie YinY Eugene Chen
Aug 26, 2009·Neurological Research·Zongduo GuoJohn H Zhang
Jan 13, 2009·Biochemical and Biophysical Research Communications·Seong-Ryong LeeJong-Wook Park
Mar 24, 2009·Journal of Pharmacological Sciences·Ravinder K KaundalShyam S Sharma

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