Pioglitazone Prevents Hemorrhagic Infarction After Transient Focal Ischemia in Type 2 Diabetes. (September 2021)

• Record Type: Journal Article
• Authors: Hasegawa, Hiroshi; Yatomi, Kenji; Mitome-Mishima, Yumiko; Miyamoto, Nobukazu; Tanaka, Ryota; Oishi, Hidenori; Arai, Hajime; Hattori, Nobutaka; Urabe, Takao
• Is Part Of: Neuroscience research. Volume 170(2021)
• Page Start: 314
• Page End: 321
• Publication Date: 2021-09
• Subjects: PPAR-γ agonist -- adiponectin -- matrix metalloproteinase 9 -- type 2 diabetes -- hemorrhagic infarction -- neuroprotective effect; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2020.09.004
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: PGZ ameliorates insulin sensitivity and improves glucose intolerance in db/db mice. PGZ prevents hemorrhagic infarction and preserves BBB integrity in db/db mice. PGZ increases plasma APN levels. PGZ may have neuroprotective effects against stroke via an APN-related mechanism. Abstract: Pioglitazone (PGZ), a PPARγ agonist, has been used for diabetic patients as an insulin-sensitizing agent. Recent studies have demonstrated that PGZ increases adiponectin (APN) levels and provides vascular protection in ischemic conditions. This study was designed to assess the neuroprotective effects of PGZ against cerebral ischemia–reperfusion injury via an APN-related mechanism. Type 2 diabetic leptin-deficient mice ( db/db ) were administered PGZ for 1 week, and plasma insulin and APN levels were measured. These mice received a middle cerebral artery occlusion and reperfusion injury, and they were evaluated for the infarct volume and by immunohistochemistry and western blotting analysis at several time points after ischemia. PGZ-administered db/db mice showed improved insulin sensitivity, and the hemorrhagic rate and infarct volume were decreased ( P < 0.05). In the PGZ-administered group, plasma APN levels increased compared with the vehicle group. In the db/db group, PGZ administration significantly suppressed inflammatory reactions and oxidative stress after reperfusion ( P < 0.05). PGZ may be applicable for acute cerebral ischemia treatment in metabolic syndrome patients as well as antidiabetic agents.