Peroxisome proliferator-activated receptor-gamma ligands reduce inflammation and infarction size in transient focal ischemia.

Sundararajan S, Gamboa JL, Victor NA, Wanderi EW, Lust WD, Landreth GE
Neuroscience. 2005 130 (3): 685-96

PMID: 15590152 · DOI:10.1016/j.neuroscience.2004.10.021

Newly developed insulin-sensitizing agents, which target the nuclear receptor peroxisome proliferator-activated receptor-gamma have recently been appreciated to exhibit potent anti-inflammatory actions. Since stroke is associated with an intense inflammatory response, we reasoned that these agents may ameliorate injury from stroke. We report that administration of troglitazone or pioglitazone 24 h before and at the time of cerebral infarction dramatically reduced infarction volume and improved neurological function following middle cerebral artery occlusion in rats. Furthermore, we find that delayed therapy also significantly reduced infarct volume. The brains of the drug-treated animals displayed reduced inflammation as evidenced by decreased immunoreactivity for microglial/macrophage markers and reduced protein and mRNA for interleukin-1beta, cyclooxygenase-2 and inducible nitric oxide synthase. We argue that the beneficial effects of these drugs are likely due to reduced expression of these inflammatory mediators, which are known to exacerbate ischemic injury following stroke. These results are of particular relevance to diabetic patients chronically treated with these agents who may benefit from the neuroprotective actions of these drugs.

MeSH Terms (26)

Animals Blood Glucose Brain Chemistry Cell Count Cerebrovascular Circulation Chromans Dose-Response Relationship, Drug Encephalitis Immunohistochemistry Infarction, Middle Cerebral Artery Ischemic Attack, Transient Ligands Macrophages Male Microglia Middle Cerebral Artery Nerve Tissue Proteins Pioglitazone PPAR gamma Psychomotor Performance Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Thiazolidinediones Troglitazone

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