ArticlePloS one2014
Early MEK1/2 inhibition after global cerebral ischemia in rats reduces brain damage and improves outcome by preventing delayed vasoconstrictor receptor upregulation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- CGRP-targeted migraine treatment and early pathophysiology in experimental subarachnoid hemorrhage.The journal of headache and pain · 2026Article
- Relationships of Jugular Bulb Parameters with Cerebral Perfusion and Metabolism After Resuscitation from Cardiac Arrest: A Post-Hoc Analysis of Experimental Studies Using a Minipig Model.Neurocritical care · 2025Article
- The MEK Inhibitor Trametinib Improves Outcomes following Subarachnoid Haemorrhage in Female Rats.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Effects of Sodium Nitroprusside Administered Via a Subdural Intracranial Catheter on the Microcirculation, Oxygenation, and Electrocortical Activity of the Cerebral Cortex in a Pig Cardiac Arrest Model.Journal of the American Heart Association · 2022Article
- Changes in P2YPhysiological reports · 2022Article
- Brain size reductions associated with endothelin B receptor mutation, a cause of Hirschsprung's disease.BMC neuroscience · 2021Article
- IMCC: A Novel Quantitative Approach Revealing Variation of Global Modular Map and Local Inter-Module Coordination Among Differential Drug's Targeted Cerebral Ischemic Networks.Frontiers in pharmacology · 2021Article
- Blockade of Acid-Sensing Ion Channels Attenuates Recurrent Hypoglycemia-Induced Potentiation of Ischemic Brain Damage in Treated Diabetic Rats.Neuromolecular medicine · 2019Article
- Safflor yellow B reduces hypoxia-mediated vasoconstriction by regulating endothelial micro ribonucleic acid/nitric oxide synthase signaling.Oncotarget · 2017Article
- Alterations in the Cerebral Microvascular Proteome Expression Profile After Transient Global Cerebral Ischemia in Rat.Journal of molecular neuroscience : MN · 2017Article
- Improved assessment of outcomes following transient global cerebral ischemia in mice.Experimental brain research · 2016Article
- Increased cerebrovascular sensitivity to endothelin-1 in a rat model of obstructive sleep apnea: a role for endothelin receptor B.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlobal cerebral ischemia following cardiac arrest is associated with increased cerebral vasoconstriction and decreased cerebral blood flow, contributing to delayed neuronal cell death and neurological detriments in affected patients. We hypothesize that upregulation of contractile ETB and 5-HT1B receptors, previously demonstrated in cerebral arteries after experimental global ischemia, are a key mechanism behind insufficient perfusion of the post-ischemic brain, proposing blockade of this receptor upregulation as a novel target for prevention of cerebral hypoperfusion and delayed neuronal cell death after global cerebral ischemia. The aim was to characterize the time-course of receptor upregulation and associated neuronal damage after global ischemia and investigate whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and thereby improve functional outcome after global cerebral ischemia. Incomplete global cerebral ischemia was induced in Wistar rats and the time-course of enhanced contractile responses and the effect of U0126 in cerebral arteries were studied by wire myography and the neuronal cell death by TUNEL. The expression of ETB and 5-HT1B receptors was determined by immunofluorescence.
resultsEnhanced vasoconstriction peaked in fore- and midbrain arteries 3 days after ischemia. Neuronal cell death appeared initially in the hippocampus 3 days after ischemia and gradually increased until 7 days post-ischemia. Treatment with U0126 normalised cerebrovascular ETB and 5-HT1B receptor expression and contractile function, reduced hippocampal cell death and improved survival rate compared to vehicle treated animals.
conclusionsExcessive cerebrovascular expression of contractile ETB and 5-HT1B receptors is a delayed response to global cerebral ischemia peaking 3 days after the insult, which likely contributes to the development of delayed neuronal damage. The enhanced cerebrovascular contractility can be prevented by treatment with the MEK1/2 inhibitor U0126, diminishes neuronal damage and improves survival rate, suggesting MEK1/2 inhibition as a novel strategy for early treatment of neurological consequences following global cerebral ischemia.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.