Abstract
White matter damage caused by cerebral hypoperfusion is a major hallmark of subcortical ischemic vascular dementia (SIVD), which is the most common subtype of vascular cognitive impairment and dementia (VCID) syndrome. In an aging society, the number of SIVD patients is expected to increase; however, effective therapies have yet to be developed. To understand the pathological mechanisms, we analyzed the profiles of the cells of the corpus callosum after cerebral hypoperfusion in a preclinical SIVD model. We prepared cerebral hypoperfused mice by subjecting 2-month old male C57BL/6J mice to bilateral carotid artery stenosis (BCAS) operation. BCAS-hypoperfusion mice exhibited cognitive deficits at 4 weeks after cerebral hypoperfusion, assessed by novel object recognition test. RNA samples from the corpus callosum region of sham- or BCAS-operated mice were then processed using RNA sequencing. A gene set enrichment analysis using differentially expressed genes between sham and BCAS-operated mice showed activation of oligodendrogenesis pathways along with angiogenic responses. This database of transcriptomic profiles of BCAS-hypoperfusion mice will be useful for future studies to find a therapeutic target for SIVD.
Highlights
Vascular cognitive impairment and dementia (VCID) syndrome is clinically defined as cognitive decline with evidence of subcortical brain infarction (Erkinjuntti et al, 2000a,b)
One major innovation of this study is the study of gene expression in the corpus callosum region using RNA Sequencing (RNAseq)
White matter dysfunction is a major feature of many CNS diseases; ; basic research of CNS diseases has mostly focused on the pathological mechanisms of gray matter
Summary
Vascular cognitive impairment and dementia (VCID) syndrome is clinically defined as cognitive decline with evidence of subcortical brain infarction (Erkinjuntti et al, 2000a,b). Hypoperfused-BCAS mice replicate the pathophysiology of SIVD patients, such as oligodendrocyte/myelin damage and cognitive decline (Ihara and Tomimoto, 2011; Ihara et al, 2014). This model has been used in various pharmacological studies investigating the treatment of SIVD, which led to the discovery of the potential efficacy of some drugs that are currently approved for other clinical indications (Watanabe et al, 2006; Ueno et al, 2009; Miyamoto et al, 2013a, 2014). In this study, we utilized the mouse cerebral hypoperfusion model of SIVD to examine the gene expression changes in the corpus callosum region after cerebral hypoperfusion
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
