title: White matter injury due to experimental chronic cerebral hypoperfusion is associated with C5 deposition.
abstract: The C5 complement protein is a potent inflammatory mediator that has been implicated in the pathogenesis of both stroke and neurodegenerative disease. Microvascular failure is proposed as a potential mechanism of injury. Along these lines, this investigation examines the role of C5 in the setting of chronic cerebral hypoperfusion. Following experimental bilateral carotid artery stenosis, C5 protein deposition increases in the corpus callosum over thirty days (p<0.05). The time course is temporally consistent with the appearance of white matter injury. Concurrently, systemic serum C5 levels do not appear to differ between bilateral carotid artery stenosis and sham-operated mice, implicating a local cerebral process. Following bilateral carotid artery stenosis, C5 deficient mice demonstrate decreased white matter ischemia in the corpus callosum when compared to C5 sufficient controls (p<0.05). Further, the C5 deficient mice exhibit fewer reactive astrocytes and microglia (p<0.01). This study reveals that the C5 complement protein may play a critical role in mediating white matter injury through inflammation in the setting of chronic cerebral hypoperfusion.
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Shuhan
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Leonid
authors.initials: L
authors.lastname: Groysman
authors.affiliation: Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Shaked
authors.affiliation: Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Russin
authors.affiliation: Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, United States.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Scotton
authors.affiliation: Department of Preventative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Cen
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America ; Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Mack
mesh_terms: D000818:Animals; D016893:Carotid Stenosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002531:Cerebellum / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D003182:Complement C5 / Q000235:genetics / Q000378:metabolism*; D003337:Corpus Callosum / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D066127:White Matter / Q000098:blood supply / Q000293:injuries / Q000378:metabolism / Q000473:pathology
chemical_list: D003182:Complement C5