title: The role of neuroglobin in the neuroprotection of limb ischemic preconditioning in rats.
abstract: Recent evidence suggests that limb ischemic preconditioning (LIP) protects neurons against cerebral ischemia-reperfusion injury. However, the mechanisms of LIP are not well understood. Neuroglobin (Ngb) is a recently discovered globin that affords protection against hypoxic/ischemic brain injury. This study was performed to investigate the role of Ngb in the neuroprotection of LIP against brain ischemia and the involvements of mitochondria in the process. The rat global brain ischemic model was used, and the CA1 hippocampus was selected as the observational target. Ngb expression was investigated by RT-PCR and Western blot. Neuropathological evaluation was performed by thionin staining. Mitochondrial membrane potential (Δψm), Na(+)-K(+)-ATPase activity, and ultrastructure were examined by flow cytometry, spectrophotometry, and transmission electron microscopy, respectively. We also used Ngb antisense oligodeoxynucleotides (AS-ODNs) and Ngb inducer hemin to inhibit or mimic the effect of LIP. We found that LIP significantly up-regulated Ngb expression and protected neurons against ischemia. Furthermore, LIP effectively improved deterioration in the Δψm, mitochondrial Na(+)-K(+)-ATPase activity, and ultrastructure induced by cerebral ischemia. These effects of LIP were inhibited partly by Ngb AS-ODNs and mimicked by hemin. It could be concluded that up-regulation of Ngb expression played an important role in the neuroprotection induced by LIP, and the Ngb-mediated neuroprotection of LIP was, at least partly, associated with mitochondria.
authors.affiliation: Department of Pathophysiology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, China.
authors.forename: Shu-Qin
authors.initials: SQ
authors.lastname: Li
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Yu-Zhou
authors.initials: YZ
authors.lastname: Wu
authors.forename: Yu-Yan
authors.initials: YY
authors.lastname: Hu
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005121:Extremities / Q000098:blood supply* / Q000473:pathology*; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D019194:Ischemic Preconditioning; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000078787:Neuroglobin; D018696:Neuroprotective Agents / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018696:Neuroprotective Agents; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D006427:Hemin; D005914:Globins