title: Peroxisome Proliferator-Activated Receptor β/δ Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Z.T., L.J., Y.W., Z.H., F.C., C.C., X.S., Zongduo Guo); Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, and Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Q.H.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, China (Y.H.); and Department of Neurology, the First Hospital of Jilin University, Changchun, China (Zhenni Guo).
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Teng
authors.affiliation: From the Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Z.T., L.J., Y.W., Z.H., F.C., C.C., X.S., Zongduo Guo); Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, and Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Q.H.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, China (Y.H.); and Department of Neurology, the First Hospital of Jilin University, Changchun, China (Zhenni Guo).
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: From the Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Z.T., L.J., Y.W., Z.H., F.C., C.C., X.S., Zongduo Guo); Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, and Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Q.H.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, China (Y.H.); and Department of Neurology, the First Hospital of Jilin University, Changchun, China (Zhenni Guo).
authors.forename: Qin
authors.initials: Q
authors.lastname: Hu
authors.affiliation: From the Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Z.T., L.J., Y.W., Z.H., F.C., C.C., X.S., Zongduo Guo); Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, and Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Q.H.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, China (Y.H.); and Department of Neurology, the First Hospital of Jilin University, Changchun, China (Zhenni Guo).
authors.forename: Yue
authors.initials: Y
authors.lastname: He
authors.affiliation: From the Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Z.T., L.J., Y.W., Z.H., F.C., C.C., X.S., Zongduo Guo); Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, and Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Q.H.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, China (Y.H.); and Department of Neurology, the First Hospital of Jilin University, Changchun, China (Zhenni Guo).
authors.forename: Zhenni
authors.initials: Z
authors.lastname: Guo
authors.affiliation: From the Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Z.T., L.J., Y.W., Z.H., F.C., C.C., X.S., Zongduo Guo); Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, and Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Q.H.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, China (Y.H.); and Department of Neurology, the First Hospital of Jilin University, Changchun, China (Zhenni Guo).
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: From the Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Z.T., L.J., Y.W., Z.H., F.C., C.C., X.S., Zongduo Guo); Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, and Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Q.H.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, China (Y.H.); and Department of Neurology, the First Hospital of Jilin University, Changchun, China (Zhenni Guo).
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Huang
authors.affiliation: From the Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Z.T., L.J., Y.W., Z.H., F.C., C.C., X.S., Zongduo Guo); Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, and Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Q.H.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, China (Y.H.); and Department of Neurology, the First Hospital of Jilin University, Changchun, China (Zhenni Guo).
authors.forename: Fang
authors.initials: F
authors.lastname: Cao
authors.affiliation: From the Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Z.T., L.J., Y.W., Z.H., F.C., C.C., X.S., Zongduo Guo); Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, and Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Q.H.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, China (Y.H.); and Department of Neurology, the First Hospital of Jilin University, Changchun, China (Zhenni Guo).
authors.forename: Chongjie
authors.initials: C
authors.lastname: Cheng
authors.affiliation: From the Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Z.T., L.J., Y.W., Z.H., F.C., C.C., X.S., Zongduo Guo); Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, and Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Q.H.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, China (Y.H.); and Department of Neurology, the First Hospital of Jilin University, Changchun, China (Zhenni Guo). sunxch1445@qq.com stonegzd@163.com.
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: From the Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Z.T., L.J., Y.W., Z.H., F.C., C.C., X.S., Zongduo Guo); Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, and Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Q.H.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, China (Y.H.); and Department of Neurology, the First Hospital of Jilin University, Changchun, China (Zhenni Guo). sunxch1445@qq.com stonegzd@163.com.
authors.forename: Zongduo
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D047494:PPAR delta / Q000096:biosynthesis*; D048068:PPAR-beta / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000473:pathology
chemical_list: D047494:PPAR delta; D048068:PPAR-beta
keywords: MMP-9; PPARβ/δ; apoptosis; early brain injury; subarachnoid hemorrhage