Models of neurovascular coupling via potassium and EET signalling

Farr, Hannah; Todem, David

doi:10.1016/j.jtbi.2011.07.006

Cited by 61 publications

(84 citation statements)

References 52 publications

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“…K þ flows into the adjacent astrocytic endfoot depolarizing the astrocyte membrane. It should be noted that Farr and David (2011) refer to this current as the sodiumpotassium (Na-K) pump current, but this is not entirely accurate. The Na-K pump is a mechanism present in the astrocyte synapseadjacent processes that exchanges sodium (Na þ ) ions for K þ ions: three Na þ ions are released for every two K þ ions that enter the astrocyte.…”

Section: Overview Of the Modelmentioning

confidence: 99%

“…The dilation occurs after neural activity triggers a series of chemical and electrical reactions in adjacent astrocytes, glial cells with long extending processes whose endfeet wrap around arterioles and neural synapses (Haydon and Carmignoto, 2006;McCaslin et al, 2011;Halassa et al, 2007). Significant work has been done investigating the vascular response to neural and astrocytic inputs (Bennett et al, 2008;Farr and David, 2011;Filosa et al, 2004) but very little has been done to explore the effect that vascular activities may have on neurons and astrocytes. The hemo-neural hypothesis, proposed by Moore and Cao (2008), implies that the cerebral vasculature has pivotal effects on neural function through a variety of direct and indirect mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…A previous model for the astrocyte signaling cascade, in which the astrocyte signals to the arteriole by releasing epoxyeicosatrienoic acid (EET), has been reported by Bennett et al (2008). Since then, Farr and David (2011) developed this model further to include an EET-dependent potassium (K þ ) release, which activated inward-rectifier potassium (KIR) channels in the arteriole smooth muscle cell (SMC), leading to SMC relaxation and vasodilation. We adapt these models along with a model for small arteries by Gonzalez-Fernandez and Ermentrout (1994) that takes into account the viscoelastic nature of the arteriole wall along with its electrical and biochemical properties.…”

Section: Introductionmentioning

confidence: 99%

“…We adapt these models along with a model for small arteries by Gonzalez-Fernandez and Ermentrout (1994) that takes into account the viscoelastic nature of the arteriole wall along with its electrical and biochemical properties. Here, we combine and significantly extend the models of Gonzalez-Fernandez and Ermentrout (1994), Bennett et al (2008), and Farr and David (2011) by adding a signaling mechanism in the reverse directionfrom vessels to astrocytes -resulting in the first bidirectional neurovascular model. This is also the first model to predict the interactions of astrocytes with vessels experiencing vasomotion.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A bidirectional model for communication in the neurovascular unit

Witthoft

Karniadakis

2012

Journal of Theoretical Biology

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Section: Overview Of the Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A bidirectional model for communication in the neurovascular unit

Witthoft

Karniadakis

2012

Journal of Theoretical Biology

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“…Full details of the phenomenological model will be presented in a forthcoming publication. David and Moore (2008), Alastruey et al (2007), David et al (2010), and Farr and David (2011) provide more background.…”

Section: Cerebrovascular Autoregulation Modelmentioning

confidence: 99%

Numerical techniques for dynamic resistive networks

Brown

2013

ANZIAMJ

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We consider approaches to the numerical difficulties posed by modelling resistive networks with dynamically changing resistances according to a set of coupled ordinary differential equations (odes). The prototype problem is autoregulation on a cerebral microvascular network. In this network the amount of perfusion, or tissue blood supply, is determined by the resistance of the vascular network. This resistance can be dynamically altered to regulate the amount of blood flow and hence maintain a balance of chemicals and nutrients in the tissue. The mechanisms responsible for this are primarily local, and are due to various chemical pathways to the vascular smooth muscle cells lining the arterioles and arteries in the vasculature. These cells contract and dilate, which alters the radii and hence resistance of the vessels. Contents C172Because of the global coupling induced by the resistive network, the resulting stiff system of odes has a dense Jacobian which precludes the direct application of traditional implicit numerical solution methods. We consider a means of remedying this problem by taking a block diagonal Jacobian approximation which allows use of an implicit method but retains the desirable property of explicit solvers of linear solution time scaling with problem size. Subject class: 65L99

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The role of astrocytic calcium and TRPV4 channels in neurovascular coupling

2017

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Neuronal activity evokes a localised change in cerebral blood flow in a response known as neurovascular coupling (NVC). Although NVC has been widely studied the exact mechanisms that mediate this response remain unclear; in particular the role of astrocytic calcium is controversial. Mathematical modelling can be a useful tool for investigating the contribution of various signalling pathways towards NVC and for analysing the underlying cellular mechanisms. The lumped parameter model of a neurovascular unit with both potassium and nitric oxide (NO) signalling pathways and comprised of neurons, astrocytes, and vascular cells has been extended to include the glutamate induced astrocytic calcium pathway with epoxyeicosatrienoic acid (EET) signalling and the stretch dependent TRPV4 calcium channel on the astrocytic endfoot. Results show that the potassium pathway governs the fast onset of vasodilation while the NO pathway has a delayed response, maintaining dilation longer following neuronal stimulation. Increases in astrocytic calcium concentration via the calcium signalling pathway and/or TRPV4 channel to levels consistent with experimental data are insufficient for inducing either vasodilation or constriction, in contrast to a number of experimental results. It is shown that the astrocyte must depolarise in order to produce a significant potassium flux through the astrocytic BK channel. However astrocytic calcium is shown to strengthen potassium induced NVC by opening the BK channel further, consequently allowing more potassium into the perivascular space. The overall effect is vasodilation with a higher maximal vessel radius.

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Models of neurovascular coupling via potassium and EET signalling

Cited by 61 publications

References 52 publications

A bidirectional model for communication in the neurovascular unit

A bidirectional model for communication in the neurovascular unit

Numerical techniques for dynamic resistive networks

The role of astrocytic calcium and TRPV4 channels in neurovascular coupling

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