title: PPARgamma agonist pioglitazone reduces matrix metalloproteinase-9 activity and neuronal damage after focal cerebral ischemia.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Medicine and Brain Research Institute, Keimyung University, Taegu, South Korea.
authors.forename: Seong-Ryong
authors.initials: SR
authors.lastname: Lee
authors.forename: Hahn-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Jung-Suk
authors.initials: JS
authors.lastname: Hong
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Baek
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
mesh_terms: 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*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone