title: Adrenomedullin deficiency and aging exacerbate ischemic white matter injury after prolonged cerebral hypoperfusion in mice.
abstract: Adrenomedullin was originally isolated from pheochromocytoma cells and reduces insulin resistance by decreasing oxidative stress. White matter lesions induced by aging and hyperglycemia play a crucial role in cognitive impairment in poststroke patients. Here, we examine whether adrenomedullin deficiency and aging exacerbate ischemic white matter injury after prolonged cerebral hypoperfusion. Adrenomedullin heterozygous, wild-type young/aged mice were subjected to prolonged hypoperfusion. Prolonged cerebral hypoperfusion followed by immunohistochemical analysis was used to evaluate white matter injury. After prolonged hypoperfusion, white matter damage progressed in a time-dependent manner in AM(+/-) group compared with the wild-type group. The number of oligodendrocyte progenitor cells gradually increased after prolonged hypoperfusion, whereas oligodendrocytes decreased following a transient increase, but the ratio of increase was mild in the AM(+/-) group (P < 0.05). Oxidative stress was detected in oligodendrocytes, with a larger increase in the AM(+/-) group (P < 0.05). Aged mice showed the same tendency, but white matter damage was worse, especially in the aged AM(+/-) group. Our results demonstrated that white matter injury was increased in adrenomedullin deficiency, which induced oxidative stress. White matter injury was more exacerbated because of hyperglycemia in aged AM(+/-) group. Adrenomedullin may be an important target in the control of ischemic white matter injury.
authors.affiliation: Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Mitome-Mishima
authors.affiliation: Department of Neurology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Miyamoto
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Department of Clinical Laboratory, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shimosawa
authors.affiliation: Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan ; Department of Neuroendovascular Therapy, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Oishi
authors.affiliation: Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Arai
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Department of Neurology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Urabe
mesh_terms: D053607:Adrenomedullin / Q000172:deficiency* / Q000235:genetics; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002908:Chronic Disease; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D066127:White Matter / Q000293:injuries* / Q000378:metabolism / Q000473:pathology
chemical_list: D053607:Adrenomedullin