The ins and outs of the BCCAo model for chronic hypoperfusion: a multimodal and longitudinal MRI approach.
Cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAo) in rodents has been proposed as an experimental model of white matter damage and vascular dementia. However, the histopathological and behavioral alterations reported in this model are variable and a full characterization of the dynamic alterations is not available. Here we implemented a longitudinal multimodal magnetic resonance imaging (MRI) design, including time-of-flight angiography, high resolution T1-weighted images, T2 relaxometry mapping, diffusion tensor imaging, and cerebral blood flow measurements up to 12 weeks after BCCAo or sham-operation in Wistar rats. Changes in MRI were related to behavioral performance in executive function tasks and histopathological alterations in the same animals. MRI frequently (70%) showed various degrees of acute ischemic lesions, ranging from very small to large subcortical infarctions. Independently, delayed MRI changes were also apparent. The patterns of MRI alterations were related to either ischemic necrosis or gliosis. Progressive microstructural changes revealed by diffusion tensor imaging in white matter were confirmed by observation of myelinated fiber degeneration, including severe optic tract degeneration. The latter interfered with the visually cued learning paradigms used to test executive functions. Independently of brain damage, BCCAo induced progressive arteriogenesis in the vertebrobasilar tree, a process that was associated with blood flow recovery after 12 weeks. The structural alterations found in the basilar artery were compatible with compensatory adaptive changes driven by shear stress. In summary, BCCAo in rats induces specific signatures in multimodal MRI that are compatible with various types of histological lesion and with marked adaptive arteriogenesis.
Experimental 7T MRI Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain ; Department of Brain Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.
Guadalupe
G
Soria
Raúl
R
Tudela
Ana
A
Márquez-Martín
Lluïsa
L
Camón
Dafnis
D
Batalle
Emma
E
Muñoz-Moreno
Elisenda
E
Eixarch
Josep
J
Puig
Salvador
S
Pedraza
Elisabet
E
Vila
Alberto
A
Prats-Galino
Anna M
AM
Planas
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000473:pathology*; D001488:Basilar Artery / Q000473:pathology; D001522:Behavior, Animal; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000601:surgery; D017536:Carotid Artery, Common / Q000473:pathology*; D002908:Chronic Disease; D003287:Contrast Media; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D064847:Multimodal Imaging; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014795:Visual Pathways / Q000473:pathology
D003287:Contrast Media