From Mechanisms to Medicine: Neurovascular Coupling in the Diagnosis and Treatment of Cerebrovascular Disorders: A Narrative Review

Lu Yang; Wenbo Zhao; Yuan Kan; Changhong Ren; Xunming Ji

doi:10.3390/cells14010016

journal article Open Access Dec 27, 2024

From Mechanisms to Medicine: Neurovascular Coupling in the Diagnosis and Treatment of Cerebrovascular Disorders: A Narrative Review

Lu Yang

Cells Vol. 14 No. 1 pp. 16 · MDPI AG

View at Publisher Save 10.3390/cells14010016

Abstract

Neurovascular coupling (NVC) refers to the process of local changes in cerebral blood flow (CBF) after neuronal activity, which ensures the timely and adequate supply of oxygen, glucose, and substrates to the active regions of the brain. Recent clinical imaging and experimental technology advancements have deepened our understanding of the cellular mechanisms underlying NVC. Pathological conditions such as stroke, subarachnoid hemorrhage, cerebral small vascular disease, and vascular cognitive impairment can disrupt NVC even before clinical symptoms appear. However, the complexity of the underlying mechanism remains unclear. This review discusses basic and clinical experimental evidence on how neural activity sensitively communicates with the vasculature to cause spatial changes in blood flow in cerebrovascular diseases. A deeper understanding of how neurovascular unit-related cells participate in NVC regulation is necessary to better understand blood flow and nerve activity recovery in cerebrovascular diseases.

Topics

No keywords indexed for this article. Browse by subject →

References

163

[1]

Gagliano, G., Monteverdi, A., Casali, S., Laforenza, U., Wheeler-Kingshott, C.A.M.G., D’angelo, E., and Mapelli, L. (2022). Non-Linear Frequency Dependence of Neurovascular Coupling in the Cerebellar Cortex Implies Vasodilation–Vasoconstriction Competition. Cells, 11. 10.3390/cells11061047

[2]

Bazargani "Astrocyte calcium signaling: The third wave" Nat. Neurosci. (2016) 10.1038/nn.4201

[3]

Balbi "Acute changes in neurovascular reactivity after subarachnoid hemorrhage in vivo" J. Cereb. Blood Flow Metab. (2017) 10.1177/0271678x15621253

[4]

Zhang "Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling" Nat. Neurosci. (2024) 10.1038/s41593-023-01515-0

[5]

Wang "Altered resting-state neurovascular coupling in patients with pontine infarction" Exp. Gerontol. (2023) 10.1016/j.exger.2023.112241

[6]

Attwell "Glial and neuronal control of brain blood flow" Nature (2010) 10.1038/nature09613

[7]

Kisler "Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease" Nat. Rev. Neurosci. (2017) 10.1038/nrn.2017.48

[8]

Muoio "The neurovascular unit—Concept review" Acta Physiol. (2014) 10.1111/apha.12250

[9]

Inocencio, I.M., Kaur, N., Tran, N.T., and Wong, F.Y. (2023). Cerebral haemodynamic response to somatosensory stimulation in preterm lambs is enhanced following sildenafil and inhaled nitric oxide administration. Front. Physiol., 14. 10.3389/fphys.2023.1101647

[10]

Mughal "The post-arteriole transitional zone: A specialized capillary region that regulates blood flow within the CNS microvasculature" J. Physiol. (2023) 10.1113/jp282246

[11]

Understanding calcium waves and sparks in central neurons

William N. Ross

Nature Reviews Neuroscience 2012 10.1038/nrn3168

[12]

Noor "Neurovascular coupling during deep brain stimulation" Brain Stimul. (2020) 10.1016/j.brs.2020.03.005

[13]

Gan "Glymphatic influx and clearance are accelerated by neurovascular coupling" Nat. Neurosci. (2023) 10.1038/s41593-023-01327-2

[14]

Fast Hemodynamic Responses in the Visual Cortex of the Awake Mouse

M. Andrea Pisauro, Neel T. Dhruv, Matteo Carandini et al.

The Journal of Neuroscience 2013 10.1523/jneurosci.2130-13.2013

[15]

Iddings "Enhanced parenchymal arteriole tone and astrocyte signaling protect neurovascular coupling mediated parenchymal arteriole vasodilation in the spontaneously hypertensive rat" J. Cereb. Blood Flow Metab. (2015) 10.1038/jcbfm.2015.31

[16]

Sotero "Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis" Nat. Commun. (2016) 10.1038/ncomms11934

[17]

Lecrux "Pyramidal neurons are “neurogenic hubs” in the neurovascular coupling response to whisker stimulation" J. Neurosci. (2011) 10.1523/jneurosci.4943-10.2011

[18]

Lecrux "Pyramidal cells and cytochrome P450 epoxygenase products in the neurovascular coupling response to basal fore-brain cholinergic input" J. Cereb. Blood Flow Metab. (2012) 10.1038/jcbfm.2012.4

[19]

Kocharyan "Specific subtypes of cortical GABA interneurons contribute to the neurovascular coupling response to basal forebrain stimulation" J. Cereb. Blood Flow Metab. (2008) 10.1038/sj.jcbfm.9600558

[20]

Han "Neurovascular Coupling under Chronic Stress Is Modified by Altered GABAergic Interneuron Activity" J. Neurosci. (2019) 10.1523/jneurosci.1357-19.2019

[21]

Vazquez "Inhibitory Neuron Activity Contributions to Hemodynamic Responses and Metabolic Load Examined Using an Inhibitory Optogenetic Mouse Model" Cereb. Cortex (2018) 10.1093/cercor/bhy225

[22]

Echagarruga "nNOS-expressing interneurons control basal and behaviorally evoked arterial dilation in somatosensory cortex of mice" eLife (2020) 10.7554/elife.60533

[23]

The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease

Costantino Iadecola

Neuron 2017 10.1016/j.neuron.2017.07.030

[24]

Krueger "CNS pericytes: Concepts, misconceptions, and a way out" Glia (2010) 10.1002/glia.20898

[25]

Lu "Astrocyte-induced cortical vasodilation is mediated by D-serine and endothelial nitric oxide synthase" Proc. Natl. Acad. Sci. USA (2013) 10.1073/pnas.1215929110

[26]

Lacroix "COX-2-Derived Prostaglandin E2 Produced by Pyramidal Neurons Contributes to Neurovascular Coupling in the Rodent Cerebral Cortex" J. Neurosci. (2015) 10.1523/jneurosci.0651-15.2015

[27]

Uhlirova "Cell type specificity of neurovascular coupling in cerebral cortex" eLife (2016) 10.7554/elife.14315

[28]

Mishra "Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles" Nat. Neurosci. (2016) 10.1038/nn.4428

[29]

Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation

Micaela Zonta, María Cecilia Angulo, Sara Gobbo et al.

Nature Neuroscience 2003 10.1038/nn980

[30]

Takano "Astrocyte-mediated control of cerebral blood flow" Nat. Neurosci. (2006) 10.1038/nn1623

[31]

Nizar "In vivo stimulus-induced vasodilation occurs without IP3 receptor activation and may precede astrocytic calcium in-crease" J. Neurosci. (2013) 10.1523/jneurosci.3285-12.2013

[32]

Filosa "Local potassium signaling couples neuronal activity to vasodilation in the brain" Nat. Neurosci. (2006) 10.1038/nn1779

[33]

Lind "Rapid stimulus-evoked astrocyte Ca2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo" Proc. Natl. Acad. Sci. USA (2013) 10.1073/pnas.1310065110

[34]

Institoris "Astrocytes amplify neurovascular coupling to sustained activation of neocortex in awake mice" Nat. Commun. (2022) 10.1038/s41467-022-35383-2

[35]

Rosenegger "Tonic Local Brain Blood Flow Control by Astrocytes Independent of Phasic Neurovascular Coupling" J. Neurosci. (2015) 10.1523/jneurosci.1780-15.2015

[36]

Hatakeyama "Differential pial and penetrating arterial responses examined by optogenetic activation of astrocytes and neurons" J. Cereb. Blood Flow Metab. (2021) 10.1177/0271678x211010355

[37]

Longden "Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow" Nat. Neurosci. (2017) 10.1038/nn.4533

[38]

Capillary pericytes regulate cerebral blood flow in health and disease

Catherine N. Hall, Clare Reynell, Bodil Gesslein et al.

Nature 2014 10.1038/nature13165

[39]

Gu "Long-term optical imaging of neurovascular coupling in mouse cortex using GCaMP6f and intrinsic hemodynamic signals" NeuroImage (2018) 10.1016/j.neuroimage.2017.09.055

[40]

Fekete "Microglia monitor and protect neuronal function through specialized somatic purinergic junctions" Science (2020) 10.1126/science.aax6752

[41]

Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions

Eszter Császár, Nikolett Lénárt, Csaba Cserép et al.

Journal of Experimental Medicine 2022 10.1084/jem.20211071

[42]

Negative feedback control of neuronal activity by microglia

Ana Badimon, Hayley J. Strasburger, Pinar Ayata et al.

Nature 2020 10.1038/s41586-020-2777-8

[43]

Toth "Purinergic glio-endothelial coupling during neuronal activity: Role of P2Y1 receptors and eNOS in functional hyperemia in the mouse somatosensory cortex" Am. J. Physiol. Circ. Physiol. (2015) 10.1152/ajpheart.00463.2015

[44]

Chen "A critical role for the vascular endothelium in functional neurovascular coupling in the brain" J. Am. Heart Assoc. (2014) 10.1161/jaha.114.000787

[45]

Endothelial NMDA receptors mediate activity-dependent brain hemodynamic responses in mice

Adam D. Hogan-Cann, Ping Lu, Christopher M. Anderson

Proceedings of the National Academy of Sciences 2019 10.1073/pnas.1902647116

[46]

Sonkusare "Inward rectifier potassium (Kir2.1) channels as end-stage boosters of endothelium-dependent vasodilators" J. Physiol. (2016) 10.1113/jp271652

[47]

Turner "CVN-AD Alzheimer’s mice show premature reduction in neurovascular coupling in response to spreading depression and anoxia compared to aged controls" Alzheimer’s Dement. (2021) 10.1002/alz.12289

[48]

Mapelli "Granular Layer Neurons Control Cerebellar Neurovascular Coupling Through an NMDA Receptor/NO-Dependent System" J. Neurosci. (2017) 10.1523/jneurosci.2025-16.2016

[49]

The pericyte connectome: spatial precision of neurovascular coupling is driven by selective connectivity maps of pericytes and endothelial cells and is disrupted in diabetes

Tamas Kovacs-Oller, Elena Ivanova, Paola Bianchimano et al.

Cell Discovery 2020 10.1038/s41421-020-0180-0

[50]

Thakore "Brain endothelial cell TRPA1 channels initiate neurovascular coupling" eLife (2021) 10.7554/elife.63040

Showing 50 of 163 references

Metrics

14

Citations

163

References

Details

Published: Dec 27, 2024
Vol/Issue: 14(1)
Pages: 16
License: View

Authors

L

Lu Yang

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

W

Wenbo Zhao

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100054, China

Y

Yuan Kan

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

C

Changhong Ren

Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100054, China; Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

X

Xunming Ji

Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100054, China; Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

Funding

National Natural Science Foundation of China Award: JQ22020

Beijing Natural Science Foundation Award: JQ22020

National Key R&D Program of China Award: JQ22020

Cite This Article

Lu Yang, Wenbo Zhao, Yuan Kan, et al. (2024). From Mechanisms to Medicine: Neurovascular Coupling in the Diagnosis and Treatment of Cerebrovascular Disorders: A Narrative Review. Cells, 14(1), 16. https://doi.org/10.3390/cells14010016

From Mechanisms to Medicine: Neurovascular Coupling in the Diagnosis and Treatment of Cerebrovascular Disorders: A Narrative Review

You May Also Like