Biphasic Functional Regulation in Hippocampus of Rat with Chronic Cerebral Hypoperfusion Induced by Permanent Occlusion of Bilateral Common Carotid Artery

BackgroundChronic cerebral hypoperfusion induced by permanent occlusion of the bilateral common carotid artery (BCCAO) in rats has been commonly used for the study of Alzheimer’s disease and vascular dementia. Despite the apparent cognitive dysfunction in rats with BCCAO, the molecular markers or pathways involved in the pathological alternation have not been clearly identified.MethodsTemporal changes (sham, 21, 35, 45, 55 and 70 days) in gene expression in the hippocampus of rats after BCCAO were measured using time-course microarray analysis. Gene Ontology (GO) and pathway analyses were performed to identify the functional involvement of temporally regulated genes in BCCAO.ResultsTwo major gene expression patterns were observed in the hippocampus of rats after BCCAO. One pattern, which was composed of 341 early up-regulated genes after the surgical procedure, was dominantly involved in immune-related biological functions (false discovery rate [FDR]FADD and SOCS3 as possible core genes in the sensory function loss process using text-based mining and interaction network analysis.ConclusionsThe biphasic regulatory mechanism first reported here could provide molecular evidence of BCCAO-induced impaired memory in rats as well as mechanism of the development of vascular dementia.