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Acute Ablation of Cortical Pericytes Leads to Rapid Neurovascular Uncoupling
dc.creator | Kisler, Kassandra | |
dc.creator | Nikolakopoulou, Angeliki M. | |
dc.creator | Sweeney, Melanie D. | |
dc.creator | Lazić, Divna | |
dc.creator | Zhao, Zhen | |
dc.creator | Zloković, Berislav V. | |
dc.date.accessioned | 2020-05-08T10:49:03Z | |
dc.date.available | 2020-05-08T10:49:03Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 1662-5102 | |
dc.identifier.uri | https://www.frontiersin.org/article/10.3389/fncel.2020.00027/full | |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/3663 | |
dc.description.abstract | Pericytes are perivascular mural cells that enwrap brain capillaries and maintain blood-brain barrier (BBB) integrity. Most studies suggest that pericytes regulate cerebral blood flow (CBF) and oxygen delivery to activated brain structures, known as neurovascular coupling. While we have previously shown that congenital loss of pericytes leads over time to aberrant hemodynamic responses, the effects of acute global pericyte loss on neurovascular coupling have not been studied. To address this, we used our recently reported inducible pericyte-specific Cre mouse line crossed to iDTR mice carrying Cre-dependent human diphtheria toxin (DT) receptor, which upon DT treatment leads to acute pericyte ablation. As expected, DT led to rapid progressive loss of pericyte coverage of cortical capillaries up to 50% at 3 days post-DT, which correlated with approximately 50% reductions in stimulus-induced CBF responses measured with laser doppler flowmetry (LDF) and/or intrinsic optical signal (IOS) imaging. Endothelial response to acetylcholine, microvascular density, and neuronal evoked membrane potential responses remained, however, unchanged, as well as arteriolar smooth muscle cell (SMC) coverage and functional responses to adenosine, as we previously reported. Together, these data suggest that neurovascular uncoupling in this model is driven by pericyte loss, but not other vascular deficits or neuronal dysfunction. These results further support the role of pericytes in CBF regulation and may have implications for neurological conditions associated with rapid pericyte loss such as hypoperfusion and stroke, as well as conditions where the exact time course of global regional pericyte loss is less clear, such as Alzheimer's disease (AD) and other neurogenerative disorders. | en |
dc.publisher | Frontiers Media SA | |
dc.relation | National Institutes of Health (R01AG039452, R01NS100459, R01AG023084, R01NS090904, R01NS034467) | |
dc.relation | Foundation Leducq Transatlantic Network of Excellence (16 CVD 05) | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | Frontiers in Cellular Neuroscience | |
dc.subject | Intrinsic optical signal imaging | |
dc.subject | Acute pericyte ablation | |
dc.subject | Capillary | |
dc.subject | Cerebral blood flow | |
dc.subject | Laser Doppler flowmetry | |
dc.subject | Neurovascular coupling | |
dc.subject | Voltage sensitive dye imaging | |
dc.title | Acute Ablation of Cortical Pericytes Leads to Rapid Neurovascular Uncoupling | en |
dc.type | article | en |
dc.rights.license | BY | |
dcterms.abstract | Лазић, Дивна; Николакопоулоу, Aнгелики М.; Кислер, Кассандра; Зхао, Зхен; Злоковић, Берислав В.; Сwеенеy, Мелание Д.; | |
dc.rights.holder | © 2020 Kisler, Nikolakopoulou, Sweeney, Lazic, Zhao and Zlokovic. | |
dc.citation.volume | 14 | |
dc.identifier.doi | 10.3389/fncel.2020.00027 | |
dc.identifier.pmid | 32116568 | |
dc.identifier.scopus | 2-s2.0-85083913078 | |
dc.identifier.wos | 000517522500001 | |
dc.citation.apa | Kisler, K., Nikolakopoulou, A. M., Sweeney, M. D., Lazic, D., Zhao, Z., & Zlokovic, B. V. (2020). Acute Ablation of Cortical Pericytes Leads to Rapid Neurovascular Uncoupling. Frontiers in Cellular Neuroscience, 14, 27. | |
dc.citation.vancouver | Kisler K, Nikolakopoulou AM, Sweeney MD, Lazic D, Zhao Z, Zlokovic B V. Acute Ablation of Cortical Pericytes Leads to Rapid Neurovascular Uncoupling. Front Cell Neurosci. 2020;14:27. | |
dc.citation.spage | 27 | |
dc.type.version | publishedVersion | |
dc.citation.rank | M22 |
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