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])

Hänggi, Daniel; Etminan, Nima; Aldrich, François; Steiger, Hans Jakob; Mayer, Stephan A.; Diringer, Michael N.; Hoh, Brian L.; Mocco, J; Faleck, Herbert; Macdonald, R. Loch

doi:10.1161/strokeaha.116.014250

Cited by 58 publications

(28 citation statements)

References 34 publications

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“…In the last 15 years, monitorization of SDs in patients after stroke and brain trauma at intensive care units has been established in multiple centers under the framework of Co-Operative Studies on Brain Injury Depolarizations (COSBID). More than 500 patients have been monitored in multiple centers in various countries, and multiple trials are currently in process, such as DISCHARGE-1, Invasive and Non-Invasive Monitoring of Spreading Depolarization by Electrocorticography in Trauma and Stroke (INSPECT), NEWTON trial (Nimodipine microparticles to Enhance recovery While reducing TOxicity after subarachNoid hemorrhage) and MHS trials [158]. Although the monitorization of the actual patients pointed out some pathological pathways, there have also been some limitations of human trials of SDs.…”

Section: Introductionmentioning

confidence: 99%

Spreading Depolarization Waves in Neurological Diseases: A Short Review about its Pathophysiology and Clinical Relevance

Tas

Solaroğlu

Gürsoy‐Özdemir

2019

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Lesion growth following acutely injured brain tissue after stroke, subarachnoid hemorrhage and traumatic brain injury is an important issue and a new target area for promising therapeutic interventions. Spreading depolarization or peri-lesion depolarization waves were demonstrated as one of the significant contributors of continued lesion growth. In this short review, we discuss the pathophysiology for SD forming events and try to list findings detected in neurological disorders like migraine, stroke, subarachnoid hemorrhage and traumatic brain injury in both human as well as experimental studies. Pharmacological and non-pharmacological treatment strategies are highlighted and future directions and research limitations are discussed.

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Section: Introductionmentioning

confidence: 99%

Spreading Depolarization Waves in Neurological Diseases: A Short Review about its Pathophysiology and Clinical Relevance

Tas

Solaroğlu

Gürsoy‐Özdemir

2019

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“…Nimodipine, an oral calcium channel blocker first introduced in 1985, was the drug typically used to treat SAH and was suggested to effectively prevent neuroischaemic events after SAH . A recent randomized trial showed that the intrathecal application of nimodipine not only reduces DCI, but also improves clinical outcome and that this approach is safe . Other vasodilators, such as fasudil, clazosentan and nicardipine, have also been shown to have some potential value for the treatment of vasoconstriction, although they may induce systemic hypotension and cerebral perfusion pressure …”

Section: The Pathophysiology Of Sahmentioning

confidence: 99%

The role and therapeutic potential of heat shock proteins in haemorrhagic stroke

Shao

Zhou

Yao

et al. 2019

J Cellular Molecular Medi

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Heat shock proteins (HSPs) are induced after haemorrhagic stroke, which includes subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH). Most of these proteins function as neuroprotective molecules to protect cerebral neurons from haemorrhagic stroke and as markers to indicate cellular stress or damage. The most widely studied HSPs in SAH are HSP70, haeme oxygenase‐1 (HO‐1), HSP20 and HSP27. The subsequent pathophysiological changes following SAH can be divided into two stages: early brain injury and delayed cerebral ischaemia, both of which determine the outcome for patients. Because the mechanisms of HSPs in SAH are being revealed and experimental models in animals are continually maturing, new agents targeting HSPs with limited side effects have been suggested to provide therapeutic potential. For instance, some pharmaceutical agents can block neuronal apoptosis signals or dilate cerebral vessels by modulating HSPs. HO‐1 and HSP70 are also critical topics for ICH research, which can be attributed to their involvement in pathophysiological mechanisms and therapeutic potential. However, the process of HO‐1 metabolism can be toxic owing to iron overload and the activation of succedent pathways, for example, the Fenton reaction and oxidative damage; the overall effect of HO‐1 in SAH and ICH tends to be protective and harmful, respectively, given the different pathophysiological changes in these two types of haemorrhagic stroke. In the present study, we focus on the current understanding of the role and therapeutic potential of HSPs involved in haemorrhagic stroke. Therefore, HSPs may be potential therapeutic targets, and new agents targeting HSPs are warranted.

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“…Those include transluminal balloon angioplasty and intra-arterial drug administration; typical agents include verapamil, papaverine, nimodipine, and milrinone. Current areas of study include nitric oxide donors, endothelin-1 antagonists, low-dose heparin, and intrathecal agents; the NEWTON2 trial is currently underway to evaluate intraventricular sustained-release nimodipine for SAH [ 38 ]. Opportunities exist for developing sustained-release spasmolytics, as well as intra-arterial neuroprotectants that could be injected during the time of standard intra-arterial treatments for vasospasm.…”

Section: Conference Proceedings—october 4–5 2017mentioning

confidence: 99%

Uncovering the Rosetta Stone: Report from the First Annual Conference on Key Elements in Translating Stroke Therapeutics from Pre-Clinical to Clinical

Bix

Fraser

Mack

et al. 2018

Transl. Stroke Res.

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The first annual Stroke Translational Research Advancement Workshop (STRAW), entitled “Uncovering the Rosetta Stone: Key Elements in Translating Stroke Therapeutics from Pre-Clinical to Clinical” was held at the University of Kentucky on October 4–5, 2017. This workshop was organized by the Center for Advanced Translational Stroke Science. The workshop consisted of 2 days of activities. These included three presentations establishing the areas of research in stroke therapeutics, discussing the routes for translation from bench to bedside, and identifying successes and failures in the field. On day 2, grant funding opportunities and goals for the National Institute for Neurological Diseases and Stroke were presented. In addition, the meeting also included break-out sessions designed to connect researchers in areas of stroke, and to foster potential collaborations. Finally, the meeting concluded with an open discussion among attendees led by a panel of experts.

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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])

Abstract: Supplemental Digital Content is available in the text.

Cited by 58 publications

References 34 publications

Spreading Depolarization Waves in Neurological Diseases: A Short Review about its Pathophysiology and Clinical Relevance

Spreading Depolarization Waves in Neurological Diseases: A Short Review about its Pathophysiology and Clinical Relevance

The role and therapeutic potential of heat shock proteins in haemorrhagic stroke

Uncovering the Rosetta Stone: Report from the First Annual Conference on Key Elements in Translating Stroke Therapeutics from Pre-Clinical to Clinical

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