title: Protective effects of recombinant human bone morphogenetic protein-7 on focal cerebral ischemia-reperfusion injury.
abstract: This study was to investigate the protective effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) on focal cerebral ischemia-reperfusion (IR) injuries and their underlying mechanisms. An intraluminal suture method was used to generate a middle cerebral artery occlusion model in rats, which was followed by reperfusion. A sham operation (SO) group underwent the procedure without occlusion, whereas an IR group and rhBMP-7 treated group (RT) underwent occlusion in the absence and presence of rhBMP-7 (250 μg/kg) administered via a femoral vein injection 30 minutes prior to reperfusion. Twenty-four hours after reperfusion, neurological function, brain water content and morphological alterations were examined. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assays, and immunohistochemical staining and Western blot assays were used to detect nuclear nuclear factor-kappa B (NF-κB) p65 expression. Compared with the SO group, IR rats showed a decrease in neurological function, an increase in brain water content, and pathological and morphological damage (p < 0.05). Higher levels of apoptosis were also detected in the infarct region area. In contrast, RT rats had reduced injury after IR. In addition, while immunohistochemical staining and western blot assays consistently detected increased expression of nuclear NF-κB after IR, these levels were reduced in the RT group. Administration of rhBMP-7 prior to reperfusion effectively inhibited the extent of IR injury by attenuating cerebral edema and ameliorating ultrastructural damage. The underlying mechanisms responsible for these observations potentially involve the inhibition of apoptosis induced by IR by rhBMP-7 via an NF-κB-related signaling cascade.
authors: Department of Anesthesiology, General Hospital of Shenyang Military Region, Shenyang, China.
authors: Ji-Hong
authors: JH
authors: Xu
authors: Tie-Zheng
authors: TZ
authors: Zhang
authors: Yan-Yan
authors: YY
authors: Zhao
authors: Jun-Ke
authors: JK
authors: Wang
authors: Zhi-Guo
authors: ZG
authors: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D055419:Bone Morphogenetic Protein 7 / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D001929:Brain Edema / Q000150:complications / Q000188:drug therapy; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D016328:NF-kappa B / Q000096:biosynthesis; D009422:Nervous System Diseases / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D014867:Water / Q000378:metabolism
chemical_list: D055419:Bone Morphogenetic Protein 7; D016328:NF-kappa B; D011994:Recombinant Proteins; D014867:Water