RT Journal Article
T1 Defective hippocampal neurogenesis underlies cognitive impairment by carotid stenosis-induced cerebral hypoperfusion in mice
A1 Fraga, Enrique
A1 Medina, Violeta
A1 Cuartero Desviat, María Isabel
A1 García Culebras, Alicia
A1 Bravo Ferrer, Isabel
A1 Hernández Jiménez, Macarena
A1 García Segura, Juan Manuel
A1 Hurtado Moreno, Olivia
A1 Pradillo Justo, Jesús Miguel
A1 Lizasoaín Hernández, Ignacio
A1 Moro Sánchez, María Ángeles
AB Chronic cerebral hypoperfusion due to carotid artery stenosis is a major cause of vascular cognitive impairment and dementia (VCID). Bilateral carotid artery stenosis (BCAS) in rodents is a well-established model of VCID where most studies have focused on white matter pathology and subsequent cognitive deficit. Therefore, our aim was to study the implication of adult hippocampal neurogenesis in hypoperfusion-induced VCID in mice, and its relationship with cognitive hippocampal deficits. Mice were subjected to BCAS; 1 and 3 months later, hippocampal memory and neurogenesis/cell death were assessed, respectively, by the novel object location (NOL) and spontaneous alternation performance (SAP) tests and by immunohistology. Hypoperfusion was assessed by arterial spin labeling-magnetic resonance imaging (ASL-MRI). Hypoperfused mice displayed spatial memory deficits with decreased NOL recognition index. Along with the cognitive deficit, a reduced number of newborn neurons and their aberrant morphology indicated a remarkable impairment of the hippocampal neurogenesis. Both increased cell death in the subgranular zone (SGZ) and reduced neuroblast proliferation rate may account for newborn neurons number reduction. Our data demonstrate quantitative and qualitative impairment of adult hippocampal neurogenesis disturbances associated with cerebral hypoperfusion-cognitive deficits in mice. These findings pave the way for novel diagnostic and therapeutic targets for VCID.
SN 1662-5102
YR 2023
FD 2023
LK https://hdl.handle.net/20.500.14352/88883
UL https://hdl.handle.net/20.500.14352/88883
LA eng
NO Fraga E, Medina V, Cuartero MI, García-Culebras A, Bravo-Ferrer I, Hernández-Jiménez M, Garcia-Segura JM, Hurtado O, Pradillo JM, Lizasoain I and Moro MÁ (2023) Defective hippocampal neurogenesis underlies cognitive impairment by carotid stenosis-induced cerebral hypoperfusion in mice. Front. Cell. Neurosci. 17:1219847. doi: 10.3389/fncel.2023.1219847
NO Ministerio de Ciencia e Innovación (España) 
NO Instituto de Salud Carlos III
NO Leducq Foundation for Cardiovascular Research
NO European Commission 
DS Docta Complutense
RD 5 abr 2025