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Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection

The cerebral microcirculation holds a critical position to match the high metabolic demand by neuronal activity. Functionally, microcirculation is virtually inseparable from other nervous system cells under both physiological and pathological conditions. For successful bench-to-bedside translation o...

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Autores principales: Erdener, Şefik Evren, Dalkara, Turgay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707104/
https://www.ncbi.nlm.nih.gov/pubmed/31474933
http://dx.doi.org/10.3389/fneur.2019.00889
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author Erdener, Şefik Evren
Dalkara, Turgay
author_facet Erdener, Şefik Evren
Dalkara, Turgay
author_sort Erdener, Şefik Evren
collection PubMed
description The cerebral microcirculation holds a critical position to match the high metabolic demand by neuronal activity. Functionally, microcirculation is virtually inseparable from other nervous system cells under both physiological and pathological conditions. For successful bench-to-bedside translation of neuroprotection research, the role of microcirculation in acute and chronic neurodegenerative disorders appears to be under-recognized, which may have contributed to clinical trial failures with some neuroprotectants. Increasing data over the last decade suggest that microcirculatory impairments such as endothelial or pericyte dysfunction, morphological irregularities in capillaries or frequent dynamic stalls in blood cell flux resulting in excessive heterogeneity in capillary transit may significantly compromise tissue oxygen availability. We now know that ischemia-induced persistent abnormalities in capillary flow negatively impact restoration of reperfusion after recanalization of occluded cerebral arteries. Similarly, microcirculatory impairments can accompany or even precede neural loss in animal models of several neurodegenerative disorders including Alzheimer's disease. Macrovessels are relatively easy to evaluate with radiological or experimental imaging methods but they cannot faithfully reflect the downstream microcirculatory disturbances, which may be quite heterogeneous across the tissue at microscopic scale and/or happen fast and transiently. The complexity and size of the elements of microcirculation, therefore, require utilization of cutting-edge imaging techniques with high spatiotemporal resolution as well as multidisciplinary team effort to disclose microvascular-neurodegenerative connection and to test treatment approaches to advance the field. Developments in two photon microscopy, ultrafast ultrasound, and optical coherence tomography provide valuable experimental tools to reveal those microscopic events with high resolution. Here, we review the up-to-date advances in understanding of the primary microcirculatory abnormalities that can result in neurodegenerative processes and the combined neurovascular protection approaches that can prevent acute as well as chronic neurodegeneration.
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spelling pubmed-67071042019-08-30 Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection Erdener, Şefik Evren Dalkara, Turgay Front Neurol Neurology The cerebral microcirculation holds a critical position to match the high metabolic demand by neuronal activity. Functionally, microcirculation is virtually inseparable from other nervous system cells under both physiological and pathological conditions. For successful bench-to-bedside translation of neuroprotection research, the role of microcirculation in acute and chronic neurodegenerative disorders appears to be under-recognized, which may have contributed to clinical trial failures with some neuroprotectants. Increasing data over the last decade suggest that microcirculatory impairments such as endothelial or pericyte dysfunction, morphological irregularities in capillaries or frequent dynamic stalls in blood cell flux resulting in excessive heterogeneity in capillary transit may significantly compromise tissue oxygen availability. We now know that ischemia-induced persistent abnormalities in capillary flow negatively impact restoration of reperfusion after recanalization of occluded cerebral arteries. Similarly, microcirculatory impairments can accompany or even precede neural loss in animal models of several neurodegenerative disorders including Alzheimer's disease. Macrovessels are relatively easy to evaluate with radiological or experimental imaging methods but they cannot faithfully reflect the downstream microcirculatory disturbances, which may be quite heterogeneous across the tissue at microscopic scale and/or happen fast and transiently. The complexity and size of the elements of microcirculation, therefore, require utilization of cutting-edge imaging techniques with high spatiotemporal resolution as well as multidisciplinary team effort to disclose microvascular-neurodegenerative connection and to test treatment approaches to advance the field. Developments in two photon microscopy, ultrafast ultrasound, and optical coherence tomography provide valuable experimental tools to reveal those microscopic events with high resolution. Here, we review the up-to-date advances in understanding of the primary microcirculatory abnormalities that can result in neurodegenerative processes and the combined neurovascular protection approaches that can prevent acute as well as chronic neurodegeneration. Frontiers Media S.A. 2019-08-16 /pmc/articles/PMC6707104/ /pubmed/31474933 http://dx.doi.org/10.3389/fneur.2019.00889 Text en Copyright © 2019 Erdener and Dalkara. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Erdener, Şefik Evren
Dalkara, Turgay
Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection
title Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection
title_full Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection
title_fullStr Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection
title_full_unstemmed Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection
title_short Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection
title_sort small vessels are a big problem in neurodegeneration and neuroprotection
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707104/
https://www.ncbi.nlm.nih.gov/pubmed/31474933
http://dx.doi.org/10.3389/fneur.2019.00889
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