The PPAR-γ agonist, darglitazone, restores acute inflammatory responses to cerebral hypoxia-ischemia in the diabetic ob/ob mouse

Rashmi Kumari, Lisa B. Willing, Shyama D. Patel, J. Kyle Krady, William J. Zavadoski, E. Michael Gibbs, Susan J. Vannucci, Ian A. Simpson

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Diabetes is an increased risk factor for stroke and results in increased brain damage in experimental animals and humans. The precise mechanisms are unclear, but our earlier studies in the db/db mice suggested that the cerebral inflammatory response initiating recovery was both delayed and diminished in the diabetic mice compared with the nondiabetic db/ mice. In this study, we investigated the actions of the peroxisome proliferator-activated receptor (PPAR)-γ agonist darglitazone in treating diabetes and promoting recovery after a hypoxic-ischemic (H/I) insult in the diabetic ob/ob mouse. Male ob/ and ob/ob mice received darglitazone (1 mg/kg) for 7 days before induction of H/I. Darglitazone restored euglycemia and normalized elevated corticosterone, triglycerides, and very-low-density lipoprotein levels. Darglitazone dramatically reduced the infarct size in the ob/ob mice at 24 h of recovery compared with the untreated group (30±13% to 3.3±31.6%, n6 to 8) but did not show any significant effect in the ob/ mice. Microglial and astrocytic activation monitored by cytokine expression (interleukin-1Β and tumor necrosis factor-α) and in situ hybridization studies (bfl1 and glial fibrillary acidic protein) suggest a biphasic inflammatory response, with darglitazone restoring the compromised proinflammatory response(s) in the diabetic mouse at 4 h but suppressing subsequent inflammatory responses at 8 and 24 h in both control and diabetic mice.

Original languageEnglish (US)
Pages (from-to)352-360
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2010

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'The PPAR-γ agonist, darglitazone, restores acute inflammatory responses to cerebral hypoxia-ischemia in the diabetic ob/ob mouse'. Together they form a unique fingerprint.

  • Cite this