Modulation of Preactivation of PPAR-βon Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion
| Autor: | Yunmei Zhang, Qin He, Ruichun Zhuang, Ying Luo, Ge Kuang, Anling Xiang, Qingsong Jiang, Junqing Yang |
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| Rok vydání: | 2012 |
| Předmět: |
Agonist
medicine.medical_specialty Article Subject medicine.drug_class business.industry medicine.medical_treatment Ischemia Hippocampus Hippocampal formation GW0742 medicine.disease Neuroprotection Proinflammatory cytokine Cytokine Endocrinology lcsh:Biology (General) Internal medicine Drug Discovery medicine Pharmacology (medical) business lcsh:QH301-705.5 Research Article |
| Zdroj: | PPAR Research, Vol 2012 (2012) PPAR Research |
| ISSN: | 1687-4765 1687-4757 |
| DOI: | 10.1155/2012/209794 |
| Popis: | The aim of this study is to investigate the neuroprotective effects and relevant mechanism of GW0742, an agonist of PPAR-β, after global cerebral ischemia-reperfusion injury (GCIRI) in rats. The rats showed memory and cognitive impairment and cytomorphological change in the hippocampus neurons following GCIRI. These effects were significantly improved by pretreatment with GW0742 in the dose-dependent manner. The expressions of IL-1β, IL-6, and TNF-αwere increased after GCIRI, while the increases in these proinflammatory cytokines by GCIRI were inhibited by GW0742 pretreatment. Similarly, GW0742 pretreatment also improved the GCIRI-induced decrease in the expression of IL-10, which can act as an inhibitory cytokine to reduce cerebral ischemic injury. For another, NF-κB p65 expression was significantly increased in hippocampal neurons with apparent nuclear translocation after global cerebral IRI, and these phenomena were also largely attenuated by GW0742 pretreatment. Moreover, the mRNA and protein expressions of PPAR-βwere significantly decreased in GCIRI + GW0742 groups when compared with those in GCIRI group. Our data suggests that the PPAR-βagonist GW0742 can exert significant neuroprotective effect against GCIRI in rats via PPAR-βactivation and its anti-inflammation effect mediated by the inhibition of expression and activation of NF-κB in the hippocampus. |
| Databáze: | OpenAIRE |
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