TY - JOUR
T1 - Cerebral hypoperfusion and cognitive impairment
T2 - The pathogenic role of vascular oxidative stress
AU - Liu, Hui
AU - Zhang, Junjian
N1 - Funding Information:
The authors thank Prof. Paul G. M. Luiten (Department of Molecular Neurobiology, University of Groningen, Netherlands) for the critical modification of the manuscript and the artworks. This study was supported by grant number 30270483 from the National Natural Science Foundation of China and “the Fundamental Research Fund for the Central Universities” of China. Address correspondence to Prof. Junjian Zhang, Ph.D., M.D., Department of Neurology, Zhongnan Hospital, Wuhan University, Donghu Road 169#, Wuhan, 430071, China. E-mail: [email protected]
PY - 2012/9
Y1 - 2012/9
N2 - Alzheimer's disease (AD) and vascular dementia (VaD) are the most frequent causes of cognitive impairment in the elderly. In the pathogenesis of cognitive impairment, the association of neurodegenerative and vascular factors indicates a major role of hemodynamic abnormalities including cerebral hypoperfusion. There is also ample evidence that oxidative stress of vascular origin leads to profound alterations in cerebrovascular regulation and is crucial to cerebrovascular dysfunction in a variety of conditions that result in chronic hypoperfusion of the brain. In rodents, experimental chronic cerebral hypoperfusion (CCH) can be initiated by occlusion of the major arterial supply. This way CCH brings about mitochondrial dysfunction and protein synthesis inhibition. These effects may destroy the balance of antioxidases and reactive oxygen species (ROS) and produce oxidative damage. At the same time, oxidative injury to vascular endothelial cell, glia, and neuron impairs vascular function and neurovascular coupling, which may result in a vicious cycle of further reduction of cerebral perfusion. In clinical cases of severe cognitive dysfunction, vascular risk factors are commonly present, while cerebral hypoperfusion is often associated with vascular oxidative damage. Thus we hypothesize that cerebral hypoperfusion is one of the key factors in the development of cognitive impairment, in which vascular oxidative stress plays a major role. The approaches against cerebrovascular dysfunction, combined with antioxidants and others, might make a promising contribution to the treatment of cognitive impairment.
AB - Alzheimer's disease (AD) and vascular dementia (VaD) are the most frequent causes of cognitive impairment in the elderly. In the pathogenesis of cognitive impairment, the association of neurodegenerative and vascular factors indicates a major role of hemodynamic abnormalities including cerebral hypoperfusion. There is also ample evidence that oxidative stress of vascular origin leads to profound alterations in cerebrovascular regulation and is crucial to cerebrovascular dysfunction in a variety of conditions that result in chronic hypoperfusion of the brain. In rodents, experimental chronic cerebral hypoperfusion (CCH) can be initiated by occlusion of the major arterial supply. This way CCH brings about mitochondrial dysfunction and protein synthesis inhibition. These effects may destroy the balance of antioxidases and reactive oxygen species (ROS) and produce oxidative damage. At the same time, oxidative injury to vascular endothelial cell, glia, and neuron impairs vascular function and neurovascular coupling, which may result in a vicious cycle of further reduction of cerebral perfusion. In clinical cases of severe cognitive dysfunction, vascular risk factors are commonly present, while cerebral hypoperfusion is often associated with vascular oxidative damage. Thus we hypothesize that cerebral hypoperfusion is one of the key factors in the development of cognitive impairment, in which vascular oxidative stress plays a major role. The approaches against cerebrovascular dysfunction, combined with antioxidants and others, might make a promising contribution to the treatment of cognitive impairment.
KW - cerebral hypoperfusion
KW - cognitive impairment
KW - vascular oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=84864958466&partnerID=8YFLogxK
U2 - 10.3109/00207454.2012.686543
DO - 10.3109/00207454.2012.686543
M3 - Article
C2 - 22519891
AN - SCOPUS:84864958466
SN - 0020-7454
VL - 122
SP - 494
EP - 499
JO - International Journal of Neuroscience
JF - International Journal of Neuroscience
IS - 9
ER -