Open AccessWhite Matter Injury Due to Experimental Chronic Cerebral Hypoperfusion Is Associated with C5 Deposition
Author(s) -
Qinghai Liu,
Shuhan He,
Leonid Groysman,
David Shaked,
Jonathan J. Russin,
Steven Cen,
William J. Mack
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0084802
Subject(s) - white matter , corpus callosum , medicine , ischemia , pathogenesis , stroke (engine) , cardiology , pathology , stenosis , perfusion , inflammation , microglia , radiology , magnetic resonance imaging , mechanical engineering , engineering
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.