MEK1/2 inhibitor U0126, but not nimodipine, reduces upregulation of cerebrovascular contractile receptors after subarachnoid haemorrhage in rats

Clinical Trial Protocol: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study Comparing EG-1962 to Standard of Care Oral Nimodipine in Adults with Aneurysmal Subarachnoid Hemorrhage [NEWTON-2 (Nimodipine Microparticles to Enhance Recovery While Reducing TOxicity After SubarachNoid Hemorrhage)]

(2018) Daniel Hänggi et al.   Neurocritical Care

Smooth muscle cell-driven vascular diseases and molecular mechanisms of VSMC plasticity

(2018) Agne Frismantiene et al.   CELLULAR SIGNALLING

Endothelin receptor mediated Ca 2+ signaling in coronary arteries after experimentally induced ischemia/reperfusion injury in rat

(2017) Sarah Brøgger Kristiansen et al.   JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY

A novel multicolor flow-cytometry application for quantitative detection of receptors on vascular smooth muscle cells

(2017) Aneta Radziwon-Balicka et al.   PLoS One

Response by Hänggi and Macdonald to Letter Regarding Article, “Randomized, Open-Label, Phase 1/2a Study to Determine the Maximum Tolerated Dose of Intraventricular Sustained Release Nimodipine for Subarachnoid Hemorrhage (NEWTON [Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage])”

(2017) Daniel Hänggi et al.   STROKE

Use of solubilizers in preclinical formulations: Effect of Cremophor EL on the pharmacokinetic properties on early discovery compounds

(2016) Bo Liu et al.   EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

Aneurysmal Subarachnoid Hemorrhage and Neuroinflammation: A Comprehensive Review

(2016) Brandon Lucke-Wold et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers

(2016) Ralf G Rempe et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Simple and validated UHPLC–MS/MS analysis of nimodipine in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage

(2016) Susan Mohamed et al.   JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES

A Site-Specific, Sustained-Release Drug Delivery System for Aneurysmal Subarachnoid Hemorrhage

(2016) Daniel Hänggi et al.   Neurotherapeutics

Randomized, Open-Label, Phase 1/2a Study to Determine the Maximum Tolerated Dose of Intraventricular Sustained Release Nimodipine for Subarachnoid Hemorrhage (NEWTON [Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage])

(2016) Daniel Hänggi et al.   STROKE

Cerebrovascular endothelin-1 hyper-reactivity is associated with transient receptor potential canonical channels 1 and 6 activation and delayed cerebral hypoperfusion after forebrain ischaemia in rats

(2015) S. E. Johansson et al.   Acta Physiologica

Effect of Endothelin Receptor Antagonists on Clinically Relevant Outcomes after Experimental Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis

(2015) Kamil G Laban et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Molecular pathophysiology of cerebral edema

(2015) Jesse A Stokum et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

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

(2014) Gro K Povlsen et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial

(2014) Peter J Kirkpatrick et al.   LANCET NEUROLOGY

Plasticity of Cerebrovascular Smooth Muscle Cells After Subarachnoid Hemorrhage

(2014) Lars Edvinsson et al.   Translational Stroke Research

European Stroke Organization Guidelines for the Management of Intracranial Aneurysms and Subarachnoid Haemorrhage

(2013) Thorsten Steiner et al.   CEREBROVASCULAR DISEASES

Current Management of Delayed Cerebral Ischemia: Update from Results of Recent Clinical Trials

(2013) Shakira Brathwaite et al.   Translational Stroke Research

Regulation of enhanced cerebrovascular expression of proinflammatory mediators in experimental subarachnoid hemorrhage via the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway

(2012) Aida Maddahi et al.   Journal of Neuroinflammation

Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage

(2012) E. Sander Connolly et al.   STROKE

Vascular plasticity in cerebrovascular disorders

(2011) Lars IH Edvinsson et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Comparison of MEK/ERK pathway inhibitors on the upregulation of vascular G-protein coupled receptors in rat cerebral arteries

(2010) Hardip Sandhu et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Blockade of the MEK/ERK Pathway with a Raf Inhibitor Prevents Activation of Pro-Inflammatory Mediators in Cerebral Arteries and Reduction in Cerebral Blood Flow after Subarachnoid Hemorrhage in a Rat Model

(2010) Aida Maddahi et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Improvement in neurological outcome and abolition of cerebrovascular endothelin B and 5-hydroxytryptamine 1B receptor upregulation through mitogen-activated protein kinase kinase 1/2 inhibition after subarachnoid hemorrhage in rats

(2010) Carl Christian Larsen et al.   JOURNAL OF NEUROSURGERY

Enhanced cerebrovascular expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 via the MEK/ERK pathway during cerebral ischemia in the rat

(2009) Aida Maddahi et al.   BMC NEUROSCIENCE

Equal contribution of increased intracranial pressure and subarachnoid blood to cerebral blood flow reduction and receptor upregulation after subarachnoid hemorrhage

(2009) Saema Ansar et al.   JOURNAL OF NEUROSURGERY

DOSE‐RELATED EFFICACY OF A CONTINUOUS INTRACISTERNAL NIMODIPINE TREATMENT ON CEREBRAL VASOSPASM IN THE RAT DOUBLE SUBARACHNOID HEMORRHAGE MODEL

(2009) Daniel Hänggi et al.   NEUROSURGERY

Feasibility and safety of intrathecal nimodipine on posthaemorrhagic cerebral vasospasm refractory to medical and endovascular therapy

(2008) Daniel Hänggi et al.   CLINICAL NEUROLOGY AND NEUROSURGERY

Subtype Activation and Interaction of Protein Kinase C and Mitogen-Activated Protein Kinase Controlling Receptor Expression in Cerebral Arteries and Microvessels After Subarachnoid Hemorrhage

(2007) Saema Ansar et al.   STROKE