PPARgamma agonist pioglitazone reduces matrix metalloproteinase-9 activity and neuronal damage after focal cerebral ischemia.
Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, has shown protective effects against ischemic insult in various tissues. Pioglitazone is also reported to reduce matrix metalloproteinase (MMP) activity. MMPs can remodel extracellular matrix components in many pathological conditions. The current study was designed to investigate whether the neuroprotection of pioglitazone is related to its MMP inhibition in focal cerebral ischemia. Mice were subjected to 90 min focal ischemia and reperfusion. In gel zymography, pioglitazone reduced the upregulation of active form of MMP-9 after ischemia. In in situ zymograms, pioglitazone also reduced the gelatinase activity induced by ischemia. After co-incubation with pioglitazone, in situ gelatinase activity was directly reduced. Pioglitazone reduced the infarct volume significantly compared with controls. These results demonstrate that pioglitazone may reduce MMP-9 activity and neuronal damage following focal ischemia. The reduction of MMP-9 activity may have a possible therapeutic effect for the management of brain injury after focal ischemia.
Lee
Seong-Ryong
SR
Department of Pharmacology, School of Medicine and Brain Research Institute, Keimyung University, Taegu, South Korea.
Kim
Hahn-Young
HY
Hong
Jung-Suk
JS
Baek
Won-Ki
WK
Park
Jong-Wook
JW
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology*; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D019610:Cytoprotection; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D061965:Matrix Metalloproteinase Inhibitors; D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone