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Trends in Neurosciences Nov 2022In the brain, increases in neural activity drive changes in local blood flow via neurovascular coupling. The common explanation for increased blood flow (known as... (Review)
Review
In the brain, increases in neural activity drive changes in local blood flow via neurovascular coupling. The common explanation for increased blood flow (known as functional hyperemia) is that it supplies the metabolic needs of active neurons. However, there is a large body of evidence that is inconsistent with this idea. Baseline blood flow is adequate to supply oxygen needs even with elevated neural activity. Neurovascular coupling is irregular, absent, or inverted in many brain regions, behavioral states, and conditions. Increases in respiration can increase brain oxygenation without flow changes. Simulations show that given the architecture of the brain vasculature, areas of low blood flow are inescapable and cannot be removed by functional hyperemia. As discussed in this article, potential alternative functions of neurovascular coupling include supplying oxygen for neuromodulator synthesis, brain temperature regulation, signaling to neurons, stabilizing and optimizing the cerebral vascular structure, accommodating the non-Newtonian nature of blood, and driving the production and circulation of cerebrospinal fluid (CSF).
Topics: Humans; Neurovascular Coupling; Hyperemia; Brain; Oxygen; Hemodynamics
PubMed: 35995628
DOI: 10.1016/j.tins.2022.08.004 -
Nature Neuroscience Jun 2023Functional hyperemia, also known as neurovascular coupling, is a phenomenon that occurs when neural activity increases local cerebral blood flow. Because all biological...
Functional hyperemia, also known as neurovascular coupling, is a phenomenon that occurs when neural activity increases local cerebral blood flow. Because all biological activity produces metabolic waste, we here sought to investigate the relationship between functional hyperemia and waste clearance via the glymphatic system. The analysis showed that whisker stimulation increased both glymphatic influx and clearance in the mouse somatosensory cortex with a 1.6-fold increase in periarterial cerebrospinal fluid (CSF) influx velocity in the activated hemisphere. Particle tracking velocimetry revealed a direct coupling between arterial dilation/constriction and periarterial CSF flow velocity. Optogenetic manipulation of vascular smooth muscle cells enhanced glymphatic influx in the absence of neural activation. We propose that impedance pumping allows arterial pulsatility to drive CSF in the same direction as blood flow, and we present a simulation that supports this idea. Thus, functional hyperemia boosts not only the supply of metabolites but also the removal of metabolic waste.
Topics: Mice; Animals; Neurovascular Coupling; Hyperemia; Glymphatic System; Hemodynamics; Brain
PubMed: 37264158
DOI: 10.1038/s41593-023-01327-2 -
Physiological Reviews Apr 2015This review focuses on how blood flow to contracting skeletal muscles is regulated during exercise in humans. The idea is that blood flow to the contracting muscles... (Review)
Review
This review focuses on how blood flow to contracting skeletal muscles is regulated during exercise in humans. The idea is that blood flow to the contracting muscles links oxygen in the atmosphere with the contracting muscles where it is consumed. In this context, we take a top down approach and review the basics of oxygen consumption at rest and during exercise in humans, how these values change with training, and the systemic hemodynamic adaptations that support them. We highlight the very high muscle blood flow responses to exercise discovered in the 1980s. We also discuss the vasodilating factors in the contracting muscles responsible for these very high flows. Finally, the competition between demand for blood flow by contracting muscles and maximum systemic cardiac output is discussed as a potential challenge to blood pressure regulation during heavy large muscle mass or whole body exercise in humans. At this time, no one dominant dilator mechanism accounts for exercise hyperemia. Additionally, complex interactions between the sympathetic nervous system and the microcirculation facilitate high levels of systemic oxygen extraction and permit just enough sympathetic control of blood flow to contracting muscles to regulate blood pressure during large muscle mass exercise in humans.
Topics: Animals; Autonomic Nervous System; Blood Flow Velocity; Blood Pressure; Cardiac Output; Energy Metabolism; Exercise; Hemodynamics; Humans; Hyperemia; Muscle Contraction; Muscle, Skeletal; Oxygen; Oxygen Consumption; Regional Blood Flow; Vasodilation
PubMed: 25834232
DOI: 10.1152/physrev.00035.2013 -
International Angiology : a Journal of... Aug 2019
Topics: Consensus; Humans; Hyperemia; Lower Extremity; Pelvic Pain; Practice Guidelines as Topic; Syndrome; Varicose Veins
PubMed: 31345010
DOI: 10.23736/S0392-9590.19.04237-8 -
American Journal of Physiology.... Mar 2020Reactive hyperemia is a well-established technique for noninvasive assessment of peripheral microvascular function and a predictor of all-cause and cardiovascular... (Review)
Review
Reactive hyperemia is a well-established technique for noninvasive assessment of peripheral microvascular function and a predictor of all-cause and cardiovascular morbidity and mortality. In its simplest form, reactive hyperemia represents the magnitude of limb reperfusion following a brief period of ischemia induced by arterial occlusion. Over the past two decades, investigators have employed a variety of methods, including brachial artery velocity by Doppler ultrasound, tissue reperfusion by near-infrared spectroscopy, limb distension by venous occlusion plethysmography, and peripheral artery tonometry, to measure reactive hyperemia. Regardless of the technique used to measure reactive hyperemia, blunted reactive hyperemia is believed to reflect impaired microvascular function. With the advent of several technological advancements, together with an increased interest in the microcirculation, reactive hyperemia is becoming more common as a research tool and is widely used across multiple disciplines. With this in mind, we sought to review the various methodologies commonly used to assess reactive hyperemia and current mechanistic pathways believed to contribute to reactive hyperemia and reflect on several methodological considerations.
Topics: Blood Flow Velocity; Brachial Artery; Humans; Hyperemia; Ischemia; Microcirculation; Vasodilation
PubMed: 32022580
DOI: 10.1152/ajpregu.00339.2019 -
Scientific Reports Feb 2024In free flap operation, temporary hyperemia of the transferred flaps can often be encountered in the early postoperative period, appearing reddish and rapid capillary...
In free flap operation, temporary hyperemia of the transferred flaps can often be encountered in the early postoperative period, appearing reddish and rapid capillary refilling time, which mimics venous congestion. This study aimed to investigate the factors associated with the development of hyperemia and evaluate clinical course. Consecutive patients who underwent free flap-based reconstruction between December 2019 and October 2021 were reviewed. Independent risk factors associated with its development were assessed. Flap showing initial hyperemic features were assessed using flap blood glucose measurement (BGM). If it showed over 60 mg/dL, they were closely observed without management. Their clinical outcomes were evaluated. In total, 204 cases were analyzed, of which 35 (17.2%) showed initial hyperemia. Multivariable analyses showed that using thoracodorsal artery perforator flaps and muscle containing flaps (musculocutaneous/muscle-chimeric flaps) and conducting end-to-end arterial anastomosis (vs. end-to-side) were independent predictors. All cases with initial hyperemia showed over 60 mg/dL in BGM. The phenomenon resolved spontaneously within 6.9 h averagely. Overall perfusion-related complications developed in 10 (4.9%) cases, which rate did not differ between the two groups. Several factors might be associated with the development of initial hyperemia after free flap surgery. With proper assessment, this condition can be successfully managed without unnecessary intervention.
Topics: Humans; Free Tissue Flaps; Hyperemia; Plastic Surgery Procedures; Perforator Flap; Prognosis
PubMed: 38366051
DOI: 10.1038/s41598-024-53834-2 -
Journal of Cerebral Blood Flow and... Nov 2013The retinal vasculature supplies cells of the inner and middle layers of the retina with oxygen and nutrients. Photic stimulation dilates retinal arterioles producing... (Review)
Review
The retinal vasculature supplies cells of the inner and middle layers of the retina with oxygen and nutrients. Photic stimulation dilates retinal arterioles producing blood flow increases, a response termed functional hyperemia. Despite recent advances, the neurovascular coupling mechanisms mediating the functional hyperemia response in the retina remain unclear. In this review, the retinal functional hyperemia response is described, and the cellular mechanisms that may mediate the response are assessed. These neurovascular coupling mechanisms include neuronal stimulation of glial cells, leading to the release of vasoactive arachidonic acid metabolites onto blood vessels, release of potassium from glial cells onto vessels, and production and release of nitric oxide (NO), lactate, and adenosine from neurons and glia. The modulation of neurovascular coupling by oxygen and NO are described, and changes in functional hyperemia that occur with aging and in diabetic retinopathy, glaucoma, and other pathologies, are reviewed. Finally, outstanding questions concerning retinal blood flow in health and disease are discussed.
Topics: Animals; Arachidonic Acid; Flicker Fusion; Glucose; Humans; Hyperemia; Neurons; Oxygen; Photic Stimulation; Regional Blood Flow; Retina; Retinal Vessels; Vasodilation
PubMed: 23963372
DOI: 10.1038/jcbfm.2013.145 -
The Neuroscientist : a Review Journal... Feb 2018Neuronal activity within the brain evokes local increases in blood flow, a response termed functional hyperemia. This response ensures that active neurons receive... (Review)
Review
Neuronal activity within the brain evokes local increases in blood flow, a response termed functional hyperemia. This response ensures that active neurons receive sufficient oxygen and nutrients to maintain tissue function and health. In this review, we discuss the functions of functional hyperemia, the types of vessels that generate the response, and the signaling mechanisms that mediate neurovascular coupling, the communication between neurons and blood vessels. Neurovascular coupling signaling is mediated primarily by the vasoactive metabolites of arachidonic acid (AA), by nitric oxide, and by K. While much is known about these pathways, many contentious issues remain. We highlight two controversies, the role of glial cell Ca signaling in mediating neurovascular coupling and the importance of capillaries in generating functional hyperemia. We propose signaling pathways that resolve these controversies. In this scheme, capillary dilations are generated by Ca increases in astrocyte endfeet, leading to production of AA metabolites. In contrast, arteriole dilations are generated by Ca increases in neurons, resulting in production of nitric oxide and AA metabolites. Arachidonic acid from neurons also diffuses into astrocyte endfeet where it is converted into additional vasoactive metabolites. While this scheme resolves several discrepancies in the field, many unresolved challenges remain and are discussed in the final section of the review.
Topics: Animals; Brain; Cerebrovascular Disorders; Humans; Hyperemia
PubMed: 28403673
DOI: 10.1177/1073858417703033 -
Proceedings of the National Academy of... Apr 2021Cerebral small vessel diseases (SVDs) are a central link between stroke and dementia-two comorbidities without specific treatments. Despite the emerging consensus that...
Cerebral small vessel diseases (SVDs) are a central link between stroke and dementia-two comorbidities without specific treatments. Despite the emerging consensus that SVDs are initiated in the endothelium, the early mechanisms remain largely unknown. Deficits in on-demand delivery of blood to active brain regions (functional hyperemia) are early manifestations of the underlying pathogenesis. The capillary endothelial cell strong inward-rectifier K channel Kir2.1, which senses neuronal activity and initiates a propagating electrical signal that dilates upstream arterioles, is a cornerstone of functional hyperemia. Here, using a genetic SVD mouse model, we show that impaired functional hyperemia is caused by diminished Kir2.1 channel activity. We link Kir2.1 deactivation to depletion of phosphatidylinositol 4,5-bisphosphate (PIP), a membrane phospholipid essential for Kir2.1 activity. Systemic injection of soluble PIP rapidly restored functional hyperemia in SVD mice, suggesting a possible strategy for rescuing functional hyperemia in brain disorders in which blood flow is disturbed.
Topics: Animals; Cerebral Small Vessel Diseases; Cerebrovascular Circulation; Disease Models, Animal; Endothelial Cells; Hyperemia; Male; Mice, Transgenic; Phosphatidylinositol 4,5-Diphosphate; Potassium Channels, Inwardly Rectifying
PubMed: 33875602
DOI: 10.1073/pnas.2025998118 -
Medicina (Kaunas, Lithuania) Apr 2023: This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without... (Review)
Review
: This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without cardiovascular autonomic neuropathy (CAN). : A systematic review of randomized and nonrandomized clinical studies characterizing reactive hyperemia and autonomic activity in type 2 diabetes patients with and without CAN was performed. : Five articles showed differences in RH between healthy subjects and diabetic patients with and/or without neuropathy, while one study did not show such differences between healthy subjects and diabetic patients, but patients with diabetic ulcers had lower RH index values compared to healthy controls. Another study found no significant difference in blood flow after a muscle strain that induced reactive hyperemia between normal subjects and non-smoking diabetic patients. Four studies measured reactive hyperemia using peripheral arterial tonometry (PAT); only two found a significantly lower endothelial-function-derived measure of PAT in diabetic patients than in those without CAN. Four studies measured reactive hyperemia using flow-mediated dilation (FMD), but no significant differences were reported between diabetic patients with and without CAN. Two studies measured RH using laser Doppler techniques; one of them found significant differences in the blood flow of calf skin after stretching between diabetic non-smokers and smokers. The diabetic smokers had neurogenic activity at baseline that was significantly lower than that of the normal subjects. The greatest evidence revealed that the differences in RH between diabetic patients with and without CAN may depend on both the method used to measure hyperemia and that applied for the ANS examination as well as the type of autonomic deficit present in the patients. : In diabetic patients, there is a deterioration in the vasodilator response to the reactive hyperemia maneuver compared to healthy subjects, which depends in part on endothelial and autonomic dysfunction. Blood flow alterations in diabetic patients during RH are mainly mediated by sympathetic dysfunction. The greatest evidence suggests a relationship between ANS and RH; however, there are no significant differences in RH between diabetic patients with and without CAN, as measured using FMD. When the flow of the microvascular territory is measured, the differences between diabetics with and without CAN become evident. Therefore, RH measured using PAT may reflect diabetic neuropathic changes with greater sensitivity compared to FMD.
Topics: Humans; Autonomic Nervous System; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascular; Hyperemia; Randomized Controlled Trials as Topic; Non-Randomized Controlled Trials as Topic
PubMed: 37109728
DOI: 10.3390/medicina59040770