Abstract

Increases in brain blood flow, evoked by neuronal activity, power neural computation and form the basis of BOLD(blood-oxygen-level-dependent) functional imaging. Whether blood flow is controlled solely by arteriole smooth muscle, or also by capillary pericytes, is controversial. We demonstrate that neuronal activity and the neurotransmitter glutamate evoke the release of messengers that dilate capillaries by actively relaxing pericytes. Dilation is mediated by prostaglandin E-2, but requires nitric oxide release to suppress vasoconstricting 20-HETE synthesis. In vivo, when sensory input increases blood flow, capillaries dilate before arterioles and are estimated to produce 84% of the blood flow increase. In pathology, ischaemia evokes capillary constriction by pericytes. We show that this is followed by pericyte death in rigor, which may irreversibly constrict capillaries and damage the blood-brain barrier. Thus, pericytes are major regulators of cerebral blood flow and initiators of functional imaging signals. Prevention of pericyte constriction and death may reduce the long-lasting blood flow decrease that damages neurons after stroke.

Authors

Hall, Catherine N.;  Reynell, Clare;  Gesslein, Bodil;  Hamilton, Nicola B.;  Mishra, Anusha;  Sutherland, Brad A.;  O'Farrell, Fergus M.;  Buchan, Alastair M.;  Lauritzen, Martin;  Attwell, David

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  • Abstract, title and references ● Is the aim clear? Yes ● Is it clear what the study found and how they did it? Yes ● Is the title informative and relevant? Yes ● Are the references: ● Relevant? Yes ● Recent? Yes ● Referenced correctly? Yes ● Are appropriate key studies included? Yes Introduction/ background ● Is it clear what is already known about this topic? Yes ● Is the research question clearly outlined? Yes ● Is the research question justified given what is already known about the topic? Yes Methods ● Is the process of subject selection clear? Yes ● Are the variables defined and measured appropriately? Yes ● Are the study methods valid and reliable? To some Extent ● Is there enough detail in order to replicate the study? Yes Results ● Is the data presented in an appropriate way? Yes ● Tables and figures relevant and clearly presented? Yes ● Appropriate units, rounding, and number of decimals? Yes ● Titles, columns, and rows labelled correctly and clearly? Yes ● Categories grouped appropriately? Yes ● Does the text in the results add to the data or is it repetitive? repetitive ● Are you clear about what is a statistically significant result? Yes ● Are you clear about what is a practically meaningful result? Yes Discussion and Conclusions ● Are the results discussed from multiple angles and placed into context without being over interpreted? Yes ● Do the conclusions answer the aims of the study? To some extent ● Are the conclusions supported by references or results? Yes ● Are the limitations of the study fatal or are they opportunities to inform future research? Needs Future Research.

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  • Nitric oxide influences pericytes, as shown by the results and conclusions of a 2007 study [Majumder S, Tamilarasan KP, Kolluru GK, Muley A, Nair CM, Omanakuttan A, Murty KV, Chatterjee S. Activated pericyte attenuates endothelial functions: nitric oxide-cGMP rescues activated pericyte-associated endothelial dysfunctions. Biochem Cell Biol. 2007;85(6):709-720.]: - activated pericytes attenuate the migration, proliferation, permeability, and NO production of endothelial cells - activated pericytes restrict angiogenesis in egg yolk vascular bed models, and NO supplementation recovers 70% of the inhibition - supplementation with NO, sildenafil citrate (phosphodiesterase inhibitor), and 8-bromo-cGMP (cGMP analog) partially recovers activated-pericyte-mediated endothelium dysfunction - NO-cGMP alleviates activated-pericyte-associated endothelial dysfunction, including angiogenesis, in a cGMP-dependent manner Circulating nitric oxide increases as a result of physical exercise performance [Tsukiyama Y, Ito T, Nagaoka K, Eguchi E, Ogino K. Effects of exercise training on nitric oxide, blood pressure and antioxidant enzymes. J Clin Biochem Nutr. 2017;60(3):180-186.]. Then can it be considered that physical exercise has a prophylactic effect for the mechanism described in the paper?

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