Peroxisome Proliferator–Activated Receptor β/δ Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats
| Autor: | Xiao-Chuan Sun, Zhen-Ni Guo, Li Jiang, Zhijian Huang, Zhipeng Teng, Yue Wu, Chongjie Cheng, Yue He, Qin Hu, Fang Cao, Zongduo Guo |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Agonist medicine.medical_specialty medicine.drug_class Peroxisome proliferator-activated receptor GW0742 Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals PPAR delta Receptor PPAR-beta Evans Blue Advanced and Specialized Nursing chemistry.chemical_classification business.industry Subarachnoid Hemorrhage Extravasation Rats 030104 developmental biology Endocrinology chemistry Apoptosis Brain Injuries Anesthesia Peroxisome proliferator-activated receptor delta Neurology (clinical) Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery |
| Zdroj: | Stroke. 47:196-205 |
| ISSN: | 1524-4628 0039-2499 |
| Popis: | Background and Purpose— Early brain injury is proposed to be the primary cause of the poor outcome after subarachnoid hemorrhage (SAH), which is closely related to the neural apoptosis. To date, the relationship between peroxisome proliferator–activated receptor β/δ (PPARβ/δ) and nuclear factor-κB/matrix metalloproteinase-9 (NF-κB/MMP-9) pathway, both of which are closely related to apoptotic effects, has been poorly studied in SAH. The present study was undertaken to evaluate the effects of PPARβ/δ on early brain injury and NF-κB/MMP-9 pathway after SAH in rats. 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. |
| Databáze: | OpenAIRE |
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