ArticleProceedings of the National Academy of Sciences of the United States of America2012
Inversion of neurovascular coupling by subarachnoid blood depends on large-conductance Ca2+-activated K+ (BK) channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 110 citations in OpenAlex.
- Brain Lymphatic Dysfunction in Subarachnoid Hemorrhage: Pathophysiology and Clinical Implications.Biomolecules · 2026Review
- Cortical spreading depolarizations in stroke: Mechanisms, neuroprotective interventions, and monitoring techniques.GeroScience · 2026Review
- All Three Supersystems-Nervous, Vascular, and Immune-Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage.Translational stroke research · 2025Review
- Neurovascular coupling dysfunction in encephalopathy: pathophysiological advances and clinical implications.Frontiers in neurology · 2025Review
- Review
- A switch in the pathway of TRPC3-mediated calcium influx into brain pericytes contributes to capillary spasms after subarachnoid hemorrhage.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Predictive Value of Fibrin Fibrinogen Degradation Products-to-Potassium Ratio for Poor Functional Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Retrospective Case-Control Study.Neurocritical care · 2024Article
- Astrocyte Regulation of Cerebral Blood Flow in Health and Disease.Cold Spring Harbor perspectives in biology · 2024Review
- Cerebrovascular Effects of Alcohol Combined with Tetrahydrocannabinol.Cannabis and cannabinoid research · 2024Article
- Animal Welfare Aspects in Planning and Conducting Experiments on Rodent Models of Subarachnoid Hemorrhage.Cellular and molecular neurobiology · 2023Review
- Blood tissue Plasminogen Activator (tPA) of liver origin contributes to neurovascular coupling involving brain endothelial N-Methyl-D-Aspartate (NMDA) receptors.Fluids and barriers of the CNS · 2023Article
- The protective effect of low-dose minocycline on brain microvascular ultrastructure in a rodent model of subarachnoid hemorrhage.Histochemistry and cell biology · 2023Article
- Development of circadian neurovascular function and its implications.Frontiers in neuroscience · 2023Review
- Revisiting the Timeline of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: Toward a Temporal Risk Profile.Neurocritical care · 2022Article
- Assaying activity-dependent arteriole and capillary responses in brain slices.Neurophotonics · 2022Article
- CADASIL mutations sensitize the brain to ischemia via spreading depolarizations and abnormal extracellular potassium homeostasis.The Journal of clinical investigation · 2022Article
- The blood-brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments.Fluids and barriers of the CNS · 2022Review
- Migraine Aura, Transient Ischemic Attacks, Stroke, and Dying of the Brain Share the Same Key Pathophysiological Process in Neurons Driven by Gibbs-Donnan Forces, Namely Spreading Depolarization.Frontiers in cellular neuroscience · 2022Review
- Low neuronal metabolism during isoflurane-induced burst suppression is related to synaptic inhibition while neurovascular coupling and mitochondrial function remain intact.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Role of perivascular and meningeal macrophages in outcome following experimental subarachnoid hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
The cellular events that cause ischemic neurological damage following aneurysmal subarachnoid hemorrhage (SAH) have remained elusive. We report that subarachnoid blood profoundly impacts communication within the neurovascular unit-neurons, astrocytes, and arterioles-causing inversion of neurovascular coupling. Elevation of astrocytic endfoot Ca(2+) to ∼400 nM by neuronal stimulation or to ∼300 nM by Ca(2+) uncaging dilated parenchymal arterioles in control brain slices but caused vasoconstriction in post-SAH brain slices. Inhibition of K(+) efflux via astrocytic endfoot large-conductance Ca(2+)-activated K(+) (BK) channels prevented both neurally evoked vasodilation (control) and vasoconstriction (SAH). Consistent with the dual vasodilator/vasoconstrictor action of extracellular K(+) ([K(+)](o)), [K(+)](o) <10 mM dilated and [K(+)](o) >20 mM constricted isolated brain cortex parenchymal arterioles with or without SAH. Notably, elevation of external K(+) to 10 mM caused vasodilation in brain slices from control animals but caused a modest constriction in brain slices from SAH model rats; this latter effect was reversed by BK channel inhibition, which restored K(+)-induced dilations. Importantly, the amplitude of spontaneous astrocytic Ca(2+) oscillations was increased after SAH, with peak Ca(2+) reaching ∼490 nM. Our data support a model in which SAH increases the amplitude of spontaneous astrocytic Ca(2+) oscillations sufficiently to activate endfoot BK channels and elevate [K(+)](o) in the restricted perivascular space. Abnormally elevated basal [K(+)](o) combined with further K(+) efflux stimulated by neuronal activity elevates [K(+)](o) above the dilation/constriction threshold, switching the polarity of arteriolar responses to vasoconstriction. Inversion of neurovascular coupling may contribute to the decreased cerebral blood flow and development of neurological deficits that commonly follow SAH.
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