ArticleBMC neuroscience2013
Early events triggering delayed vasoconstrictor receptor upregulation and cerebral ischemia after subarachnoid hemorrhage.
Article in BMC neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: Experimental-Clinical Disconnect and the Unmet Need.Neurocritical care · 2020Pooled it
- Switching Off Vascular MAPK Signaling: A Novel Strategy to Prevent Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage.Translational stroke research · 2025Review
- High levels of uric acid upregulate endothelin receptors: the role of MAPK pathways in anArchives of medical science : AMS · 2025Article
- Incidence and Factors in Delayed Neurological Deficits after Subarachnoid Hemorrhage in Mice.Brain hemorrhages · 2024Article
- Changes in P2YPhysiological reports · 2022Article
- Synergistic effects of a cremophor EL drug delivery system and its U0126 cargo in anDrug delivery · 2019Article
- Preclinical update on regulation of intracranial pressure in relation to idiopathic intracranial hypertension.Fluids and barriers of the CNS · 2019Review
- The protective effect of cardamonin on the factors involved in delayed cerebral vasospasm in a rat model of subarachnoid hemorrhage.International journal of clinical and experimental pathology · 2018Article
- Proteomic Expression Changes in Large Cerebral Arteries After Experimental Subarachnoid Hemorrhage in Rat Are Regulated by the MEK-ERK1/2 Pathway.Journal of molecular neuroscience : MN · 2017Article
- Timing of Mean Transit Time Maximization is Associated with Neurological Outcome After Subarachnoid Hemorrhage.Clinical neuroradiology · 2017Article
- A pilot study on the impact of dopamine, serotonin, and brain-derived neurotrophic factor genotype on long-term functional outcomes after subarachnoid hemorrhage.SAGE open medicine · 2017Article
- A novel multicolor flow-cytometry application for quantitative detection of receptors on vascular smooth muscle cells.PloS one · 2017Article
- Aneurysmal Subarachnoid Hemorrhage and Neuroinflammation: A Comprehensive Review.International journal of molecular sciences · 2016Review
- Characteristics of Cerebrovascular Injury in the Hyperacute Phase After Induced Severe Subarachnoid Hemorrhage.Translational stroke research · 2015Article
- MEK1/2 inhibitor U0126 but not endothelin receptor antagonist clazosentan reduces upregulation of cerebrovascular contractile receptors and delayed cerebral ischemia, and improves outcome after subarachnoid hemorrhage in rats.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Article
- CaMKII inhibition with KN93 attenuates endothelin and serotonin receptor-mediated vasoconstriction and prevents subarachnoid hemorrhage-induced deficits in sensorimotor function.Journal of neuroinflammation · 2014Article
- Plasticity of cerebrovascular smooth muscle cells after subarachnoid hemorrhage.Translational stroke research · 2014Article
- Controversies and evolving new mechanisms in subarachnoid hemorrhage.Progress in neurobiology · 2014Article
- To look beyond vasospasm in aneurysmal subarachnoid haemorrhage.BioMed research international · 2014Review
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUpregulation of vasoconstrictor receptors in cerebral arteries, including endothelin B (ETB) and 5-hydroxytryptamine 1B (5-HT(1B)) receptors, has been suggested to contribute to delayed cerebral ischemia, a feared complication after subarachnoid hemorrhage (SAH). This receptor upregulation has been shown to be mediated by intracellular signalling via the mitogen activated protein kinase kinase (MEK1/2)--extracellular regulated kinase 1/2 (ERK1/2) pathway. However, it is not known what event(s) that trigger MEK-ERK1/2 activation and vasoconstrictor receptor upregulation after SAH.We hypothesise that the drop in cerebral blood flow (CBF) and wall tension experienced by cerebral arteries in acute SAH is a key triggering event. We here investigate the importance of the duration of this acute CBF drop in a rat SAH model in which a fixed amount of blood is injected into the prechiasmatic cistern either at a high rate resulting in a short acute CBF drop or at a slower rate resulting in a prolonged acute CBF drop.
resultsWe demonstrate that the duration of the acute CBF drop is determining for a) degree of early ERK1/2 activation in cerebral arteries, b) delayed upregulation of vasoconstrictor receptors in cerebral arteries and c) delayed CBF reduction, neurological deficits and mortality. Moreover, treatment with an inhibitor of MEK-ERK1/2 signalling during an early time window from 6 to 24 h after SAH was sufficient to completely prevent delayed vasoconstrictor receptor upregulation and improve neurological outcome several days after the SAH.
conclusionsOur findings suggest a series of events where 1) the acute CBF drop triggers early MEK-ERK1/2 activation, which 2) triggers the transcriptional upregulation of vasoconstrictor receptors in cerebral arteries during the following days, where 3) the resulting enhanced cerebrovascular contractility contribute to delayed cerebral ischemia.
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