From the earliest stages of development, when cerebral angiogenesis and neurogenesis are entwined, to the end of life, the interplay between vascular and neural systems of the brain is critical in health and disease. Cerebral microvascular endothelial cells constitute the blood–brain barrier and in concert with pericytes or smooth muscle cells, glia and neurons, integrate into a functional neurovascular unit (NVU). This multicellular NVU maintains homoeostasis of the brain’s microenvironment by restricting the entry of systemic pathogens and neurotoxins as well as meeting the metabolic demands of neural activity. Recent evidence of cerebral microvascular pathologies in vascular diseases and dementia, including Alzheimer’s disease, has challenged the notion that vascular events are merely the consequence of neuronal pathology. This review focuses on molecular mechanisms of neurovascular dysfunction in dementia and outlines currently employed in vitro models to decode such mechanisms. Deciphering neurovascular crosstalk is likely to be more important in understanding the molecular mechanisms of disease than previously anticipated and may offer novel therapeutic opportunities for dementia and related conditions.
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Review Article|
February 14 2018
Neurovascular dysfunction in dementia – human cellular models and molecular mechanisms
Isobel Parkes
;
Isobel Parkes
*
1
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, U.K.
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Satyan Chintawar
;
Satyan Chintawar
*
1
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, U.K.
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M. Zameel Cader
1
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, U.K.
Correspondence: M. Zameel Cader (zameel.cader@ndcn.ox.ac.uk)
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Clin Sci (Lond) (2018) 132 (3): 399-418.
Article history
Received:
July 17 2017
Revision Received:
January 15 2018
Accepted:
January 19 2018
Citation
Isobel Parkes, Satyan Chintawar, M. Zameel Cader; Neurovascular dysfunction in dementia – human cellular models and molecular mechanisms. Clin Sci (Lond) 14 February 2018; 132 (3): 399–418. doi: https://doi.org/10.1042/CS20160720
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