title: Beraprost sodium protects against chronic brain injury in aluminum-overload rats.
abstract: BACKGROUND
  Aluminum overload can cause severe brain injury and neurodegeneration. Previous studies suggest that prostacyclin synthase (PGIS) expression and prostacyclin receptor (IP) activation are beneficial for treatment of acute traumatic and ischemic brain injury. However, the potential value of PGIS/IP signaling pathway to chronic brain injury is still unclear. In this study, we investigated the change of PGIS/IP signaling pathway and the effect of beraprost sodium (BPS) on chronic brain injury in chronic aluminum-overload rats.
  
  
  METHODS
  Rat model of chronic cerebral injury was established by chronic intragastric administration of aluminum gluconate(Al3+ 200 mg/kg per day,5d a week for 20 weeks). The methods of ELISA, qRT-PCR and Western blotting were used to detect the PGI2 level and the PGIS and IP mRNA and protein levels in hippocampi of chronic aluminum-overload rats, respectively. Rat hippocampal superoxide dismutase (SOD) activity and malondialdehyde (MDA) content also were measured. The effects of BPS (6, 12 and 24 μg⋅kg(-1)) on brain injury in chronic aluminum-overload rats were evaluated.
  
  
  RESULTS
  Compared with the control group, PGIS mRNA expression, PGI2 level, and the IP mRNA and protein expressions significantly increased in hippocampi of chronic aluminum-overload rats. Administration of BPS significantly improved spatial learning and memory function impairment and hippocampal neuron injury induced by chronic aluminum overload in rats. Meanwhile, administration of BPS resulted in a decrease of PGI2 level and downregulation of PGIS and IP expressions in a dose-dependent manner. Aluminum overload also caused a decrease of SOD activity and an increase of MDA content. Administration of BPS significantly blunted the decrease of SOD activity and the increase of MDA content induced by aluminum overload in rats.
  
  
  CONCLUSIONS
  BPS has a significant neuroprotective effect on chronic brain injury induced by aluminum overload in rats. Remodeling the balance of PGIS/IP signaling pathway and inhibition of oxidative stress involve in the neuroprotective mechanism of BPS in aluminum-overload rats. The PGIS/IP signaling pathway is a potential therapeutic strategy for chronic brain injury patients.
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China. 936419719@qq.com.|Laboratory Animal Center, Chongqing Medical University, Chongqing, 400016, China. 936419719@qq.com.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China. 346521650@qq.com.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China. 675672297@qq.com.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Lei
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China. 38058480@qq.com.
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China. 314249553@qq.com.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Basic College, Chongqing Medical University, Chongqing, 400016, China. 1370748729@qq.com.
authors.forename: Huarong
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Basic College, Chongqing Medical University, Chongqing, 400016, China. ytang062@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China. 1139627371@qq.com.|Department of Pharmacology, Chongqing Medical University, Chongqing, 400010, China. 1139627371@qq.com.
authors.forename: Junqing
authors.initials: J
authors.lastname: Yang
mesh_terms: D000535:Aluminum / Q000378:metabolism; D017607:Aluminum Compounds; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001925:Brain Damage, Chronic / Q000139:chemically induced* / Q000517:prevention & control*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000627:therapeutic use; D005942:Gluconates; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control / Q000523:psychology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044006:Receptors, Epoprostenol / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017607:Aluminum Compounds; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005942:Gluconates; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D044006:Receptors, Epoprostenol; C048081:beraprost; D008315:Malondialdehyde; D003577:Cytochrome P-450 Enzyme System; D000535:Aluminum; D011464:Epoprostenol; D013482:Superoxide Dismutase; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase