scholarly journals Retinal Neurovascular Coupling in Diabetes

2020 ◽  
Vol 9 (9) ◽  
pp. 2829 ◽  
Author(s):  
Gerhard Garhöfer ◽  
Jacqueline Chua ◽  
Bingyao Tan ◽  
Damon Wong ◽  
Doreen Schmidl ◽  
...  
Keyword(s):  
Blood Flow ◽  
Diabetic Retinopathy ◽  
Molecular Mechanisms ◽  
Visual Stimulation ◽  
Neurovascular Coupling ◽  
Neural Tissue ◽  
Current Evidence ◽  
Compelling Evidence ◽  
Functional Hyperemia ◽  
Patients With Diabetes

Neurovascular coupling, also termed functional hyperemia, is one of the physiological key mechanisms to adjust blood flow in a neural tissue in response to functional activity. In the retina, increased neural activity, such as that induced by visual stimulation, leads to the dilatation of retinal arterioles, which is accompanied by an immediate increase in retinal and optic nerve head blood flow. According to the current scientific view, functional hyperemia ensures the adequate supply of nutrients and metabolites in response to the increased metabolic demand of the neural tissue. Although the molecular mechanisms behind neurovascular coupling are not yet fully elucidated, there is compelling evidence that this regulation is impaired in a wide variety of neurodegenerative and vascular diseases. In particular, it has been shown that the breakdown of the functional hyperemic response is an early event in patients with diabetes. There is compelling evidence that alterations in neurovascular coupling precede visible signs of diabetic retinopathy. Based on these observations, it has been hypothesized that a breakdown of functional hyperemia may contribute to the retinal complications of diabetes such as diabetic retinopathy or macular edema. The present review summarizes the current evidence of impaired neurovascular coupling in patients with diabetes. In this context, the molecular mechanisms of functional hyperemia in health and disease will be covered. Finally, we will also discuss how neurovascular coupling may in future be used to monitor disease progression or risk stratification.

Regulation of blood flow in diabetic retinopathy

2020 ◽  
Vol 37 ◽  
Author(s):  
Amy R. Nippert ◽  
Eric A. Newman
Keyword(s):  
Blood Flow ◽  
Diabetic Retinopathy ◽  
Neuronal Activity ◽  
Neurovascular Coupling ◽  
Functional Hyperemia ◽  
Retinal Neurons ◽  
Adequate Supply ◽  
Oxygen Levels ◽  
Signaling Mechanisms ◽  
Diabetic Brain

Abstract Blood flow in the retina increases in response to light-evoked neuronal activity, ensuring that retinal neurons receive an adequate supply of oxygen and nutrients as metabolic demands vary. This response, termed “functional hyperemia,” is disrupted in diabetic retinopathy. The reduction in functional hyperemia may result in retinal hypoxia and contribute to the development of retinopathy. This review will discuss the neurovascular coupling signaling mechanisms that generate the functional hyperemia response in the retina, the changes to neurovascular coupling that occur in diabetic retinopathy, possible treatments for restoring functional hyperemia and retinal oxygen levels, and changes to functional hyperemia that occur in the diabetic brain.

scholarly journals Functional Hyperemia and Mechanisms of Neurovascular Coupling in the Retinal Vasculature

2013 ◽  
Vol 33 (11) ◽  
pp. 1685-1695 ◽  
Author(s):  
Eric A Newman
Keyword(s):  
Blood Flow ◽  
Glial Cells ◽  
Neurovascular Coupling ◽  
Retinal Blood Flow ◽  
Retinal Vasculature ◽  
Functional Hyperemia ◽  
Cellular Mechanisms ◽  
Neuronal Stimulation ◽  
Health And Disease ◽  
Coupling Mechanisms

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.

Neurovascular coupling is not influenced by lower body negative pressure in humans

2020 ◽  
Vol 319 (1) ◽  
pp. H22-H31
Author(s):  
Milena Samora ◽  
Lauro C. Vianna ◽  
Jake C. Carmo ◽  
Victor Macedo ◽  
Matthew Dawes ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vertebral Artery ◽  
Cerebral Artery ◽  
Negative Pressure ◽  
Visual Stimulation ◽  
Posterior Cerebral Artery ◽  
Lower Body Negative Pressure ◽  
Neurovascular Coupling ◽  
Lower Body ◽  
Artery Blood Flow

Visual stimulation evoked a robust increase in posterior cerebral artery velocity and a modest increase in vertebral artery blood flow, i.e., neurovascular coupling (NVC), which was unaffected by lower body negative pressure in humans (LBNP). In addition, although LBNP induced a mild hypocapnia, this degree of hypocapnia in the absence of LBNP failed to modify the NVC response.

scholarly journals Retinal Neurodegeneration in Diabetes: an Emerging Concept in Diabetic Retinopathy

2021 ◽  
Vol 21 (12) ◽  
Author(s):  
Mira M. Sachdeva
Keyword(s):  
Diabetic Retinopathy ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Treatment Options ◽  
Retinal Disease ◽  
Vascular Pathology ◽  
Patients With Diabetes ◽  
Retinal Neurodegeneration ◽  
Diabetic Retinal Neurodegeneration

Abstract Purpose of Review Diabetic retinopathy (DR), the leading cause of blindness in working-aged adults, remains clinically defined and staged by its vascular manifestations. However, early retinal neurodegeneration may precede vascular pathology, suggesting that this neuronal damage may contribute to disease pathogenesis and represent an independent target for intervention. This review will discuss the evidence and implications for diabetic retinal neurodegeneration. Recent Findings A growing body of literature has identified progressive retinal thinning and visual dysfunction in patients with diabetes even prior to the onset of DR, though advances in retinal vascular imaging suggest that vascular remodeling and choroidal changes occur during these early stages as well. Animal models of diabetes and in vitro studies have also suggested that diabetes may directly affect the retinal neural and glial tissue, providing support to the concept that diabetic retinal neurodegeneration occurs early in the disease and suggesting potentially relevant molecular pathways. Summary Diabetic retinal neurodegeneration may represent a “preclinical” manifestation of diabetic retinal disease and remains an active area of investigation. As the natural history and molecular mechanisms become increasingly understood, it may lead to upcoming developments in not only the treatment options but also the clinical definition of DR.

scholarly journals Exhaustive Exercise Attenuates the Neurovascular Coupling by Blunting the Pressor Response to Visual Stimulation

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yuji Yamaguchi ◽  
Tsukasa Ikemura ◽  
Naoyuki Hayashi
Keyword(s):  
Blood Flow ◽  
Visual Stimulation ◽  
Pressor Response ◽  
Neurovascular Coupling ◽  
Transcranial Doppler Ultrasound ◽  
Mean Value ◽  
Exhaustive Exercise ◽  
Maximal Heart Rate ◽  
Eyes Closed ◽  
Relative Change

Neurovascular coupling (NVC) is assessed as an increase response to visual stimulation, and is monitored by blood flow of the posterior cerebral artery (PCA). To investigate whether exhaustive exercise modifies NVC, and more specifically, the relative contributions of vasodilatation in the downstream of PCA and the pressor response on NVC, we measured blood flow velocity in the PCA (PCAv) in 13 males using transcranial Doppler ultrasound flowmetry during a leg-cycle exercise at 75% of maximal heart rate until exhaustion. NVC was estimated as the relative change in PCAv from the mean value obtained during 20-s with the eyes closed to the peak value obtained during 40-s of visual stimulation involving looking at a reversed checkerboard. Conductance index (CI) was calculated by dividing PCAv by mean arterial pressure (MAP) to evaluate the vasodilatation. At exhaustion, PCAv was significantly decreased relative to baseline measurements, and the PCAv response to visual stimulation significantly decreased. Compared to baseline, exhaustive exercise significantly suppressed the increase in MAP to visual stimulation, while the CI response did not significantly change by the exercise. These results suggest that exhaustive exercise attenuates the magnitude of NVC by blunting the pressor response to visual stimulation.

scholarly journals Reversal of neurovascular coupling in the default mode network: Evidence from hypoxia

2020 ◽  
pp. 0271678X2093082
Author(s):  
Gabriella MK Rossetti ◽  
Giovanni d’Avossa ◽  
Matthew Rogan ◽  
Jamie H Macdonald ◽  
Samuel J Oliver ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Neuronal Activity ◽  
Motion Detection ◽  
Default Mode Network ◽  
Visual Stimulation ◽  
Neurovascular Coupling ◽  
Bold Response ◽  
Default Mode ◽  
Regional Specificity

Local changes in cerebral blood flow are thought to match changes in neuronal activity, a phenomenon termed neurovascular coupling. Hypoxia increases global resting cerebral blood flow, but regional cerebral blood flow (rCBF) changes are non-uniform. Hypoxia decreases baseline rCBF to the default mode network (DMN), which could reflect either decreased neuronal activity or altered neurovascular coupling. To distinguish between these hypotheses, we characterized the effects of hypoxia on baseline rCBF, task performance, and the hemodynamic (BOLD) response to task activity. During hypoxia, baseline CBF increased across most of the brain, but decreased in DMN regions. Performance on memory recall and motion detection tasks was not diminished, suggesting task-relevant neuronal activity was unaffected. Hypoxia reversed both positive and negative task-evoked BOLD responses in the DMN, suggesting hypoxia reverses neurovascular coupling in the DMN of healthy adults. The reversal of the BOLD response was specific to the DMN. Hypoxia produced modest increases in activations in the visual attention network (VAN) during the motion detection task, and had no effect on activations in the visual cortex during visual stimulation. This regional specificity may be particularly pertinent to clinical populations characterized by hypoxemia and may enhance understanding of regional specificity in neurodegenerative disease pathology.

scholarly journals Prostaglandin E2 Dilates Intracerebral Arterioles When Applied to Capillaries: Implications for Small Vessel Diseases

2021 ◽  
Vol 13 ◽  
Author(s):  
Amanda C. Rosehart ◽  
Thomas A. Longden ◽  
Nick Weir ◽  
Jackson T. Fontaine ◽  
Anne Joutel ◽  
...  
Keyword(s):  
Blood Flow ◽  
Laser Scanning ◽  
Small Vessel Disease ◽  
Ex Vivo ◽  
Neurovascular Coupling ◽  
Laser Scanning Microscopy ◽  
Small Vessel ◽  
Prostaglandin E ◽  
Functional Hyperemia ◽  
Flow Measurements

Prostaglandin E2 (PGE2) has been widely proposed to mediate neurovascular coupling by dilating brain parenchymal arterioles through activation of prostanoid EP4 receptors. However, our previous report that direct application of PGE2 induces an EP1-mediated constriction strongly argues against its direct action on arterioles during neurovascular coupling, the mechanisms sustaining functional hyperemia. Recent advances have highlighted the role of capillaries in sensing neuronal activity and propagating vasodilatory signals to the upstream penetrating parenchymal arteriole. Here, we examined the effect of capillary stimulation with PGE2 on upstream arteriolar diameter using an ex vivo capillary-parenchymal arteriole preparation and in vivo cerebral blood flow measurements with two-photon laser-scanning microscopy. We found that PGE2 caused upstream arteriolar dilation when applied onto capillaries with an EC50 of 70 nM. The response was inhibited by EP1 receptor antagonist and was greatly reduced, but not abolished, by blocking the strong inward-rectifier K+ channel. We further observed a blunted dilatory response to capillary stimulation with PGE2 in a genetic mouse model of cerebral small vessel disease with impaired functional hyperemia. This evidence casts previous findings in a different light, indicating that capillaries are the locus of PGE2 action to induce upstream arteriolar dilation in the control of brain blood flow, thereby providing a paradigm-shifting view that nonetheless remains coherent with the broad contours of a substantial body of existing literature.

Astrocytes in health and disease

2007 ◽  
Vol 148 (15) ◽  
pp. 697-702 ◽  
Author(s):  
Marianna Murányi ◽  
Zsombor Lacza
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Free Radicals ◽  
Molecular Mechanisms ◽  
Neuronal Dysfunction ◽  
Supporting Cells ◽  
Neuronal Synapses ◽  
Health And Disease ◽  
Novel Targets ◽  
Therapeutic Tools

It is now known that astrocytes are not merely supporting cells but they also play an important role in neuronal funcions. Astrocytes tightly ensheat neuronal synapses and regulate the excitation of neurons by uptaking neurotransmitters; reglulate the cerebral blood flow, cerebral fluid volume and extracellular concentrations of ions. They also supply fuel in the form of lactate and provide free radical scavangers such as glutathione for active neurons. These facts indicate that impaired function of astrocytes may lead to neuronal dysfunction. After brain injury (stroke, trauma or tumors) astrocytes are swollen and release active molecules such as glutamate or free radicals resulting in neuronal dysfunction. Thus, investigation of the molecular mechanisms of astrocyte function may reveal novel targets for the development of therapeutic tools in neuronal diseases.

Role of blood flow and impaired autoregulation in the pathogenesis of diabetic retinopathy

Diabetes ◽  
1995 ◽  
Vol 44 (6) ◽  
pp. 603-607 ◽  
Author(s):  
E. M. Kohner ◽  
V. Patel ◽  
S. M. Rassam
Keyword(s):  
Blood Flow ◽  
Diabetic Retinopathy
Sign in / Sign up

Export Citation Format

Share Document