Abstract 173: Chronic Cerebral Hypoperfusion Induces Cognitive Impairment and Aggravates the Progression of Cardiac and Renal Dysfunction

Abstract

Background: Vascular contributions to cognitive impairment and dementia (VICD) are major health problems worldwide. Heart-kidney deficit and dementia frequently coexist, but little is known whether VICD induces cardiac and kidney deficit absent from primary heart and kidney deficit. The purpose of this study was to investigate the effect of VCID on white matter (WM) injury and cognitive impairment, as well as how VCID affects heart and kidney function at 2 and 8 months after bilateral common carotid artery stenosis (BCAS) in a mouse model of VICD. Methods: Adult male C57BL/6J (8-months) mice were subjected to Sham and BCAS surgery using micro coils with inner diameter of 0.16 mm. Cognitive functional tests and cardiac function were measured before mice were sacrificed at 2 months post BCAS (2M-BCAS) and at 8 months post BCAS (8M-BCAS), respectively. The brains, hearts and kidneys were then harvested for histological and immunohistochemical (IHC) staining. Significant statistics were determined as p<0.05. Results: Compared to Sham group, mice in 2M-BCAS and 8M-BCAS group both exhibit significantly: 1) increased cognitive deficits identified by decreasing the novel object recognition (NOR) test, social interaction test and Morris water maze test. 2) increased axonal/WM injury by decreasing Bielschowsky silver and Luxol fast blue density. 3) decreased left ventricular ejection fraction (LVEF) measured by echocardiogram. 4) increased heart iba-1, cardiac and renal fibrosis indicated by picrosirius red (PSR) staining. 5) increased mesangial proliferation and thickening of the glomerular basement membrane (GBM). Compared to 2M-BCAS, 8M-BCAS mice exhibit significantly: 1) worse axonal/WM injury. 2) worse LVEF and fractional shortening (FS). 3) increased heart iba-1 expression as well as cardiac and renal fibrosis. 4) induced severer mesangial proliferation and thickening of GBM. Conclusions: Our data indicate that BCAS not only induces progressive long-term cognitive impairment and WM/axonal damage, but also induces progressive cardiac and renal dysfunction compared to sham control mice.