Permanent, bilateral common carotid artery occlusion in the rat: A model for chronic cerebral hypoperfusion-related neurodegenerative diseases

• Published in: Brain Research Reviews Vol. 54; no. 1; pp. 162 - 180
• Main Authors: Farkas, Eszter, Luiten, Paul G.M, Bari, Ferenc
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.04.2007; Elsevier
• Subjects: Animals; Biological and medical sciences; Brain - blood supply; Brain - metabolism; Brain - physiopathology; Carotid Artery, Common - physiopathology; Carotid occlusion; Carotid Stenosis - complications; Carotid Stenosis - physiopathology; Cerebral blood flow; Cerebrovascular Circulation - physiology; Cerebrovascular Disorders - complications; Cerebrovascular Disorders - physiopathology; Chronic Disease - prevention & control; Chronic Disease - therapy; Disease Models, Animal; Hippocampus; Humans; Hypoxia-Ischemia, Brain - complications; Hypoxia-Ischemia, Brain - physiopathology; Learning; Medical sciences; Neurodegenerative Diseases - etiology; Neurodegenerative Diseases - physiopathology; Neurology; Rat; Rats; Vascular diseases and vascular malformations of the nervous system; White matter; APP; matrix metalloproteinase-2; BBB; DG; IPL; Rat; cyclooxygenase-2; pyr; OPL; hippocampus CA1 stratum pyramidale; IDE; MDA; Learning; blood–brain barrier; rad; GAP-43; retina outer plexiform layer; brain-derived neurotrophic factor; malondialdehyde; Alzheimer's disease; hematoxylin–eosin; insulin-degrading enzyme; nitric oxide; AD; EEG; H&E; DG iml; permanent, bilateral common carotid artery occlusion, two-vessel occlusion; EP; myelin basic protein; electroencephalogram; α7NicR; Sec; dentate gyrus; MMP-2; growth-associated protein-43; ROS; cerebral blood flow; HPC; MAP-2; CgA; glial fibrillary acidic protein; retina inner plexiform layer; sham-operated control; NO; Cu/Zn-SOD; microtubule-associated protein-2; COX-2; Cu/Zn-superoxide dismutase; encephalitogenic peptide; CBF; glutathione; white matter; amyloid precursor protein; WM; reactive oxygen species; MBP; dentate gyrus inner molecular layer; GSH; or; hippocampus; BDNF; SHAM; 2VO; GFAP; neprilysin; Carotid occlusion; hippocampus CA1 stratum oriens; Nep; α7-nicotinic acetylcholine receptor; chromogranin A; hippocampus CA1 stratum radiatum; γ-secretase; Cerebral blood flow; White matter; Hippocampus; Occlusion; Regional blood flow; Animal model; Rodentia; Central nervous system; Cardiovascular disease; Review; Encephalon; Vertebrata; Chronic; Mammalia; Acquisition process; Ischemia; Animal; Degenerative disease; Hemodynamics
• ISSN: 0165-0173; 1872-6321
• DOI: 10.1016/j.brainresrev.2007.01.003

Abstract Chronic cerebral hypoperfusion has been associated with cognitive decline in aging and Alzheimer's disease. Moreover, the pattern of cerebral blood flow in mild cognitive impairment has emerged as a predictive marker for the progression into Alzheimer's disease. The reconstruction of a pathological condition in animal models is a suitable approach to the unraveling of causal relationships. For this reason, permanent, bilateral occlusion of the common carotid arteries (2VO) in rats has been established as a procedure to investigate the effects of chronic cerebral hypoperfusion on cognitive dysfunction and neurodegenerative processes. Over the years, the 2VO model has generated a large amount of data, revealing the 2VO-related pattern of cerebral hypoperfusion and metabolic changes, learning and memory disturbances, failure of neuronal signaling, and the neuropathological changes in the hippocampus. In addition, the model has been introduced in research into ischemic white matter injury and ischemic eye disease. The present survey sets out to provide a comprehensive summary of the achievements made with the 2VO model, and a critical evaluation and integration of the various results, and to relate the experimental data to human diseases. The data that have accumulated from use of the 2VO model in the rat permit an understanding of the causative role played by cerebral hypoperfusion in neurodegenerative diseases. Thorough characterization of the model suggests that 2VO in the rat is suitable for the development of potentially neuroprotective strategies in neurodegenerative diseases.