Regulation of cerebral microvessels by glutamatergic mechanisms

Fergus, Andrea; Lee, Kevin M.

doi:10.1016/s0006-8993(97)00040-1

Cited by 91 publications

(60 citation statements)

References 55 publications

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“…Both NMDA (Southam et al, 1991;Fergus and Lee, 1997;Lovick et al, 1999) and non-NMDA (Yang et al, 1999) receptors have been implicated in the NO-dependent microvascular dilation induced by glutamate. Stellate cells are particularly enriched with extrasynaptic NMDA receptors (Carter and Regehr, 2000;Clark and Cull-Candy, 2002;Rancillac and Crepel, 2004).…”

Section: Introductionmentioning

confidence: 99%

Glutamatergic Control of Microvascular Tone by Distinct GABA Neurons in the Cerebellum

et al. 2006

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The tight coupling between increased neuronal activity and local cerebral blood flow, known as functional hyperemia, is essential for normal brain function. However, its cellular and molecular mechanisms remain poorly understood. In the cerebellum, functional hyperemia depends almost exclusively on nitric oxide (NO). Here, we investigated the role of different neuronal populations in the control of microvascular tone by in situ amperometric detection of NO and infrared videomicroscopy of microvessel movements in rat cerebellar slices. Bath application of an NO donor induced both NO flux and vasodilation. Surprisingly, endogenous release of NO elicited by glutamate was accompanied by vasoconstriction that was abolished by inhibition of Ca 2ϩ -phopholipase A2 and impaired by cyclooxygenase and thromboxane synthase inhibition and endothelin A receptor blockade, indicating a role for prostanoids and endothelin 1 in this response. Interestingly, direct stimulation of single endothelin 1-immunopositive Purkinje cells elicited constriction of neighboring microvessels. In contrast to glutamate, NMDA induced both NO flux and vasodilation that were abolished by treatment with a NO synthase inhibitor or with tetrodotoxin. These findings indicate that NO derived from neuronal origin is necessary for vasodilation induced by NMDA and, furthermore, that NO-producing interneurons mediate this vasomotor response. Correspondingly, electrophysiological stimulation of single nitrergic stellate cells by patch clamp was sufficient to release NO and dilate both intraparenchymal and upstream pial microvessels. These findings demonstrate that cerebellar stellate and Purkinje cells dilate and constrict, respectively, neighboring microvessels and highlight distinct roles for different neurons in neurovascular coupling.

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Section: Introductionmentioning

confidence: 99%

Glutamatergic Control of Microvascular Tone by Distinct GABA Neurons in the Cerebellum

et al. 2006

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“…Whereas there is agreement that NO is essential for NMDAinduced arteriolar dilation, it is unclear whether parenchymal-derived NO can directly reach pial arterioles. Alternatively, pial arteriolar responses may follow the initial dilation of intracortical arterioles via retrograde flow-dependent vasodilation by endothelial factors (15).…”

mentioning

confidence: 99%

N-methyl-d-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets

Domoki

Perciaccante

Shimizu

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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. N-methyl-D-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets. Am J Physiol Heart Circ Physiol 282: H1404-H1409, 2002. First published November 23, 2001 10.1152/ajpheart. 00523.2001.-N-methyl-D-aspartate (NMDA) elicits pial arteriolar dilation that has been associated with neuronal nitric oxide (NO) production. However, endothelial factors or glial P-450 epoxygenase products may play a role. We tested whether NMDA-induced pial vasodilation 1) primarily involves NO diffusion from the parenchyma to the surface arterioles, 2) involves intact endothelial function, and 3) involves a miconazole-sensitive component. Arteriolar diameters were determined using closed cranial window-intravital microscopy in anesthetized piglets. NMDA (10-100 M) elicited virtually identical dose-dependent dilations in paired arterioles (r ϭ 0.94, n ϭ 15). However, NMDA-but not bradykinin (BK)-induced dilations of arteriolar sections over large veins were reduced by 31 Ϯ 1% (means Ϯ SE, P Ͻ 0.05, n ϭ 4) compared with adjacent sections on the cortical surface. Also, 100 M NMDA increased cerebrospinal fluid levels of NO metabolites from 3.7 Ϯ 1.0 to 5.3 Ϯ 1.2 M (P Ͻ 0.05, n ϭ 6). Endothelial stunning by intracarotid injection of phorbol 12,13-dibutyrate did not affect NMDA-induced vasodilation but attenuated vascular responses to hypercapnia and BK by ϳ70% (n ϭ 7). Finally, miconazole (n ϭ 6, 20 M) pretreatment and coapplication with NMDA did not alter vascular responses to NMDA. In conclusion, NMDA appears to dilate pial arterioles exclusively through release and diffusion of NO from neurons to the pial surface in piglets. cerebral circulation; miconazole; pial arterioles; bradykinin PREVIOUS STUDIES suggest that stimulation of N-methyl-D-aspartate (NMDA) receptors on cortical neurons results in dose-dependent pial arteriolar dilation via a mechanism involving neuronal nitric oxide (NO) synthase (nNOS) activation and subsequent NO release in newborn pigs (11,29). Because cerebral resistance vessels and cortical astroglia lack NMDA receptors, cerebral vasodilation to NMDA must be initiated by substances released from activated neurons (30,38). Similar involvement of NO in NMDA-induced pial arteriolar vasodilation or increased cerebral blood flow (CBF) have been observed in many other species (14,32,40). Glutamate receptor activation either by nervous or pharmacological stimulation results in increased blood flow in a variety of regions, such as the cerebral cortex (25, 33, 41), striatum (10), hippocampus (18), cerebellum (3), and medulla (16) in rats. In all these regions, NO seems to be involved in the mechanism of CBF increase, and the major glutamate receptor subtype appears to be the NMDA receptor, except in the cerebellum (3, 40). However, many of the details of this relationship between activation of NMDA receptors and cerebrovascular dilation are unclear. Whereas there is agreement that NO is essential for NMDAinduced arteriolar dilation, it is unclear whether parenchymal-derived N...

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“…As the majority of neurons within the cortex are excitatory [27] and glutamate has been known for a long time to evoke vascular dilation [28], neurovascular coupling research has primarily focused on glutamate-evoked blood flow changes. This glutamate-mediated neurovascular coupling neatly links the most energetically expensive component of synaptic transmission, ion flux through post-synaptic glutamate receptors [17,29,30], with increased energy supply.…”

Section: Cellular Mechanisms Underlying Bold: How Our Incomplete Undementioning

confidence: 99%

Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience

Hall

Howarth

Kurth-Nelson

et al. 2016

Phil. Trans. R. Soc. B

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Cognitive neuroscience depends on the use of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to probe brain function. Although commonly used as a surrogate measure of neuronal activity, BOLD signals actually reflect changes in brain blood oxygenation. Understanding the mechanisms linking neuronal activity to vascular perfusion is, therefore, critical in interpreting BOLD. Advances in cellular neuroscience demonstrating differences in this neurovascular relationship in different brain regions, conditions or pathologies are often not accounted for when interpreting BOLD. Meanwhile, within cognitive neuroscience, the increasing use of high magnetic field strengths and the development of model-based tasks and analyses have broadened the capability of BOLD signals to inform us about the underlying neuronal activity, but these methods are less well understood by cellular neuroscientists. In 2016, a Royal Society Theo Murphy Meeting brought scientists from the two communities together to discuss these issues. Here, we consolidate the main conclusions arising from that meeting. We discuss areas of consensus about what BOLD fMRI can tell us about underlying neuronal activity, and how advanced modelling techniques have improved our ability to use and interpret BOLD. We also highlight areas of controversy in understanding BOLD and suggest research directions required to resolve these issues. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’.

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Regulation of cerebral microvessels by glutamatergic mechanisms

Cited by 91 publications

References 55 publications

Glutamatergic Control of Microvascular Tone by Distinct GABA Neurons in the Cerebellum

Glutamatergic Control of Microvascular Tone by Distinct GABA Neurons in the Cerebellum

N-methyl-d-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets

Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience

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