COX-2-Derived Prostaglandin E2 Produced by Pyramidal Neurons Contributes to Neurovascular Coupling in the Rodent Cerebral Cortex

Lacroix, Alexandre; Toussay, Xavier; Anenberg, Eitan; Lecrux, Clotilde; Ferreiròs, Nerea; Karagiannis, Anastassios; Plaisier, Fabrice; Chausson, Patrick; Jarlier, Frédéric; Burgess, Sean A.; Hillman, Elizabeth M. C.; Tegeder, Irmgard; Murphy, Timothy H.; Hamel, Edith; Cauli, Bruno

doi:10.1523/jneurosci.0651-15.2015

Cited by 99 publications

(128 citation statements)

References 121 publications

Supporting

Mentioning

119

Contrasting

Order By: Relevance

“…Consistent with the activity maps, glutamate and the vasoactive COX-2 product prostaglandin E2 (PGE2) released from activated pyramidal cells have been identified as key mediators of the whisker-evoked NVC response [49,73,120], making pyramidal cells the 'hubs' of sensory-evoked NVC responses. Glutamate acts through both ionotropic (NMDA and AMPA) receptors and metabotropic receptors (mGluRs) [49,121,122] that are expressed by neurons and astrocytes [8,123].…”

Section: (A) Whisker-evoked Neurovascular Couplingmentioning

confidence: 71%

“…While technically possible, such investigations have been more rarely performed [52,67,73,75,76], and the acquisition, synchronization and interpretation of these signals in time and space still remain a challenge.…”

Section: (B) the Neurovascular Coupling Responses To Whisker Stimulationmentioning

confidence: 99%

“…Glutamate acts through both ionotropic (NMDA and AMPA) receptors and metabotropic receptors (mGluRs) [49,121,122] that are expressed by neurons and astrocytes [8,123]. The ability of NMDA receptors to rapidly trigger release of neuronal COX-2-derived PGE2 [73,124] likely accounted for the important role of PGE2 in whisker-evoked NVC [73] ( figure 3). Glutamate, however, is believed to act primarily through group 1 mGluRs to induce Ca 2þ transients in astrocytic perivascular endfeet [8,10] and activate a cascade of arachidonic acid metabolites derived from cytochrome P450 epoxygenase ( figure 3).…”

Section: (A) Whisker-evoked Neurovascular Couplingmentioning

confidence: 99%

See 2 more Smart Citations

Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states

Lecrux

Hamel

2016

Phil. Trans. R. Soc. B

Self Cite

104

103

View full text Add to dashboard Cite

One contribution of 15 to a Theo Murphy meeting issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. Brain imaging techniques that use vascular signals to map changes in neuronal activity, such as blood oxygenation level-dependent functional magnetic resonance imaging, rely on the spatial and temporal coupling between changes in neurophysiology and haemodynamics, known as 'neurovascular coupling (NVC)'. Accordingly, NVC responses, mapped by changes in brain haemodynamics, have been validated for different stimuli under physiological conditions. In the cerebral cortex, the networks of excitatory pyramidal cells and inhibitory interneurons generating the changes in neural activity and the key mediators that signal to the vascular unit have been identified for some incoming afferent pathways. The neural circuits recruited by whisker glutamatergic-, basal forebrain cholinergic-or locus coeruleus noradrenergic pathway stimulation were found to be highly specific and discriminative, particularly when comparing the two modulatory systems to the sensory response. However, it is largely unknown whether or not NVC is still reliable when brain states are altered or in disease conditions. This lack of knowledge is surprising since brain imaging is broadly used in humans and, ultimately, in conditions that deviate from baseline brain function. Using the whisker-to-barrel pathway as a model of NVC, we can interrogate the reliability of NVC under enhanced cholinergic or noradrenergic modulation of cortical circuits that alters brain states.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.

show abstract

Section: (A) Whisker-evoked Neurovascular Couplingmentioning

confidence: 71%

Section: (B) the Neurovascular Coupling Responses To Whisker Stimulationmentioning

confidence: 99%

Section: (A) Whisker-evoked Neurovascular Couplingmentioning

confidence: 99%

See 1 more Smart Citation

Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states

Lecrux

Hamel

2016

Phil. Trans. R. Soc. B

Self Cite

104

103

View full text Add to dashboard Cite

show abstract

“…30,38 Constitutive expression of cerebral COX-2, however, is limited to excitatory neurons where, unlike COX-1, it is thought to mediate neurovascular coupling. 31,32,39 The reliance on COX-1 metabolites for the transformation of the hyperemic response to oligemia following CSD suggests that despite their massive depolarization, excitatory cortical neurons which primarily express COX-2, 40,41 are unlikely to contribute. The finding that local action of TXA 2 is involved in mediating, at least in part, the initial oligemic response points potentially to the role of cortical astrocytes, which become activated during CSD 42 and are capable of releasing this vasoconstricting prostanoid.…”

Section: Discussionmentioning

confidence: 99%

Differential contribution of COX-1 and COX-2 derived prostanoids to cortical spreading depression—Evoked cerebral oligemia

Gariepy

Zhao

Levy

2016

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Cortical spreading depression (CSD) is considered a significant phenomenon for human neurological conditions and one of its key signatures is the development of persistent cortical oligemia. The factors underlying this reduction in cerebral blood flow (CBF) remain incompletely understood but may involve locally elaborated vasoconstricting eicosanoids. We employed laser Doppler flowmetry in urethane-anesthetized rats, together with a local pharmacological blockade approach, to test the relative contribution of cyclooxygenase (COX)-derived prostanoids to the oligemic response following CSD. Administration of the non-selective COX inhibitor naproxen completely inhibited the oligemic response. Selective inhibition of COX-1 with SC-560 preferentially reduced the early reduction in CBF while selective COX-2 inhibition with NS-398 affected only the later response. Blocking the action of thromboxane A 2 (TXA 2 ), using the selective thromboxane synthase inhibitor ozagrel, reduced only the initial CBF decrease, while inhibition of prostaglandin F2alpha action, using the selective FP receptor antagonist AL-8810, blocked the later phase of the oligemia. Our results suggest that the long-lasting oligemia following CSD consists of at least two distinct temporal phases, mediated by preferential actions of COX-1-and COX-2-derived prostanoids: an initial phase mediated by COX-1 that involves TXA 2 followed by a later phase, mediated by COX-2 and PGF2alpha.

show abstract

“…137 This same group recently identified a sub-population of COX-2 expressing pyramidal neurons as the primary cell type able to synthesize PGE 2 , which reportedly acts through G s -coupled EP 2 and EP 4 receptors to produce hyperemia. 137,138 However, a fundamental issue is raised by a recent study showing that application of PGE 2 directly to isolated, pressurized parenchymal arterioles from both rat and mouse evoked constriction rather than dilation, through activation of EP 1 receptors, suggesting that PGE 2 is unlikely to act as a direct mediator of NVC on parenchymal arteriole smooth muscle. 139 However, this does not rule out PGE 2 -mediated vasodilatory effects through indirect actions on neurons 139 or on the capillary endothelium.…”

Section: Arachidonic Acid Metabolitesmentioning

confidence: 99%

Ion channel networks in the control of cerebral blood flow

Longden

Hill-Eubanks

Nelson

2015

J Cereb Blood Flow Metab

119

115

View full text Add to dashboard Cite

One hundred and twenty five years ago, Roy and Sherrington made the seminal observation that neuronal stimulation evokes an increase in cerebral blood flow.1 Since this discovery, researchers have attempted to uncover how the cells of the neurovascular unit-neurons, astrocytes, vascular smooth muscle cells, vascular endothelial cells and pericytes-coordinate their activity to control this phenomenon. Recent work has revealed that ionic fluxes through a diverse array of ion channel species allow the cells of the neurovascular unit to engage in multicellular signaling processes that dictate local hemodynamics. In this review we center our discussion on two major themes: (1) the roles of ion channels in the dynamic modulation of parenchymal arteriole smooth muscle membrane potential, which is central to the control of arteriolar diameter and therefore must be harnessed to permit changes in downstream cerebral blood flow, and (2) the striking similarities in the ion channel complements employed in astrocytic endfeet and endothelial cells, enabling dual control of smooth muscle from either side of the blood-brain barrier. We conclude with a discussion of the emerging roles of pericyte and capillary endothelial cell ion channels in neurovascular coupling, which will provide fertile ground for future breakthroughs in the field.

show abstract

COX-2-Derived Prostaglandin E2 Produced by Pyramidal Neurons Contributes to Neurovascular Coupling in the Rodent Cerebral Cortex

Abstract: Vasodilatory prostaglandins play a key role in neurovascular coupling (NVC),

Cited by 99 publications

References 121 publications

Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states

Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states

Differential contribution of COX-1 and COX-2 derived prostanoids to cortical spreading depression—Evoked cerebral oligemia

Ion channel networks in the control of cerebral blood flow

Contact Info

Product

Resources

About