Abstract | BACKGROUND AND PURPOSE: METHODS: SAH model was established by injecting nonheparinized autologous arterial blood into the prechiasmatic cistern in male Sprague-Dawley rats. Adenoviruses or small interfering RNAs were injected into the right lateral cerebral ventricle to, respectively, up- or downregulate PPARβ/δ expression before SAH. All animals were assessed with a neurological score and then killed at 24 hours after SAH surgery. The indexes of brain water content, blood-brain barrier permeability, and apoptosis were used to detect brain injury. The expression of PPARβ/δ, NF-κB, and MMP-9 were measured by immunohistochemistry, gelatin zymography, and Western Blot methods, respectively. In addition, GW0742, a specific agonist of PPARβ/δ, was used to treat SAH in rats, the effects of which were evaluated by neurological scoring and Evans blue extravasation. RESULTS: Overexpression of PPARβ/δ by adenoviruses treatment significantly ameliorated brain injury with improvement in neurological deficits, brain edema, blood-brain barrier impairment, and neural cell apoptosis at 24 hours after SAH in rats, whereas downregulation of PPARβ/δ by small interfering RNAs administration resulted in the reverse effects of the above. The expression levels of NF-κB and MMP-9 were markedly downregulated when PPARβ/δ increased after PPARβ/δ adenovirus transfection and upregulated when PPARβ/δ decreased by PPARβ/δ small interfering RNAs treatment. Moreover, GW0742 improved neurological deficits and reduced Evans blue extravasation at 24 hours after SAH. CONCLUSIONS: PPARβ/δ's overexpression may attenuate early brain injury after rats' SAH administration, which reduces neural apoptosis possibly through blocking NF-κB/ MMP-9 pathway.
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Authors | Zhipeng Teng, Li Jiang, Qin Hu, Yue He, Zhenni Guo, Yue Wu, Zhijian Huang, Fang Cao, Chongjie Cheng, Xiaochuan Sun, Zongduo Guo |
Journal | Stroke
(Stroke)
Vol. 47
Issue 1
Pg. 196-205
(Jan 2016)
ISSN: 1524-4628 [Electronic] United States |
PMID | 26628385
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 American Heart Association, Inc. |
Chemical References |
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Topics |
- Animals
- Brain Injuries
(metabolism, pathology, prevention & control)
- Male
- PPAR delta
(biosynthesis)
- PPAR-beta
(biosynthesis)
- Rats
- Rats, Sprague-Dawley
- Subarachnoid Hemorrhage
(metabolism, pathology)
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