title: The temporal profile of genomic responses and protein synthesis in ischemic tolerance of the rat brain induced by repeated hyperbaric oxygen.
abstract: Repeated hyperbaric oxygen (HBO) exposure prior to ischemia has been reported to provide neuroprotection against ischemic brain injury. The present study examined the time course of neuroprotection of HBO (3.5 atmosphere absolute, 100% oxygen, 1 h for 5 consecutive days) and the changes of gene/protein expression in rats. First, at 6 h, 12 h, 24 h, and 72 h after HBO sessions, rats were subjected to forebrain ischemia (8 min). Histopathological examination of hippocampal CA1 neurons was done 7 days after ischemia. Second, temporal genomic responses and protein expression were examined at the same time points after HBO sessions without subjecting animals to ischemia. HBO significantly reduced loss of hippocampal CA1 neurons that normally follows transient forebrain ischemia when the last HBO session was 6 h, 12 h, or 24 h before ischemia (survived neurons 55%, 75%, and 53%, respectively), whereas if there was a 72-h delay before the ischemic insult, HBO was not protective (survived neurons only 6%). Statistical analysis on microarray data showed significant upregulation in 60 probe sets including 7 annotated genes (p75NTR, C/EBPdelta, CD74, Edg2, Trip10, Nrp1, and Igf2), whose time course expressions corresponded to HBO-induced neuroprotection. The protein levels of p75NTR, C/EBPdelta, and CD74 were significantly increased (maximum fold changes 2.9, 2.0, and 7.9, respectively). The results suggest that HBO-induced neuroprotection against ischemic injury has time window, protective at 6 h, 12 h and 24 h but not protective at 72 h. Although the precise interaction is to be determined, the genes/proteins relevant to neurotrophin and inflammatory-immune system may be involved in HBO-induced neuroprotection.
authors.affiliation: Department of Anesthesiology-Resuscitology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505 Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hirata
authors.forename: Ying Jun
authors.initials: YJ
authors.lastname: Cui
authors.forename: Takeshi
authors.initials: T
authors.lastname: Funakoshi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Mizukami
authors.forename: Yu-Ichiro
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Futoshi
authors.initials: F
authors.lastname: Shibasaki
authors.forename: Mishiya
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Takefumi
authors.initials: T
authors.lastname: Sakabe
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D006931:Hyperbaric Oxygenation; D019194:Ischemic Preconditioning; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D016548:Prosencephalon / Q000378:metabolism* / Q000503:physiopathology; D014176:Protein Biosynthesis / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D009419:Nerve Tissue Proteins