Experimental and Translational Stroke Medicine

Increasing evidence suggests that cell therapy improves functional recovery in experimental models of stroke and myocardial infarction. So far only small pilot trials tested the effects of cell therapy in stroke patients, whereas large clinical trials were conducted in patients with ischemic heart disease. To investigate the therapeutic benefit of cell therapy to improve the recovery after stroke, we determined the efficacy of bone marrow derived mononuclear cells, which were shown to improve the recovery in experimental and clinical acute myocardial infarction studies, in a rat stroke model. Adult male Wistar rats were randomly assigned to receive either five million human bone marrow mononuclear cells (hBMC) or placebo intraarterially 3 days after photothrombotic ischemia. For immunosuppression the animals received daily injections of cyclosporine throughout the experiment, commencing 24 hours before the cell transplantation. A battery of behavioral tests was performed before and up to 4 weeks after ischemia. Body temperature and body weight revealed no difference between groups. Neurological deficits measured by the Rotarod test, the adhesive-removal test and the cylinder test were not improved by hBMC transplantation compared to placebo. This study demonstrates that hBMC do not improve functional recovery when transplanted intraaterially 3 days after the onset of focal cerebral ischemia. A possible reason for the failed neurological improvement after cell therapy might be the delayed treatment initiation compared to other experimental stroke studies that showed efficacy of bone marrow mononuclear cells.

Jens Minnerup

Florian H Seeger

Katharina Kuhnert

Kai Diederich

Matthias Schilling

Stefanie Dimmeler

Wolf-Rüdiger Schäbitz

Experimental & Translational Stroke Medicine

Intracarotid administration of human bone marrow mononuclear cells in rat photothrombotic ischemia

颈内动脉注射人骨髓单个核细胞在大鼠光血栓性缺血中的应用

Permanent middle cerebral artery (MCA) occlusion (pMCAO) by electrocoagulation is a commonly used model but with potential traumatic lesions. Early MRI monitoring may assess pMCAO for non-specific brain damage. The surgical steps of pMCAO were evaluated for traumatic cerebral injury in 22 Swiss mice using diffusion and T2-weighted MRI (7T) performed within 1 h and 24 h after surgery. Temporal muscle cauterization without MCA occlusion produced an early T2 hyperintensity mimicking an infarct. No lesion was visible after temporal muscle incision or craniotomy. Early MRI monitoring is useful to identify non-specific brain injury that could hamper neuroprotective drugs assessment.

Fabien Chauveau

Samir Moucharrafie

Marlène Wiart

Jean-Christophe Brisset

Yves Berthezène

Norbert Nighoghossian

Tae-Hee Cho

In vivo MRI assessment of permanent middle cerebral artery occlusion by electrocoagulation: pitfalls of procedure

电凝法永久性大脑中动脉闭塞的在体MRI评估：操作中的陷阱

Abstract Background Anticoagulation is an important means to prevent from acute ischemic stroke but is associated with a significant risk of severe hemorrhages. Previous studies have shown that blood coagulation factor XII (FXII)-deficient mice are protected from pathological thrombus formation during cerebral ischemia without bearing an increased bleeding tendency. Hence, pharmacological blockade of FXII might be a promising and safe approach to prevent acute ischemic stroke and possibly other thromboembolic disorders but pharmacological inhibitors selective over FXII are still lacking. In the present study we investigated the efficacy of COU254, a novel nonpeptidic 3-carboxamide-coumarin that selectively blocks FXII activity, on stroke development and post stroke functional outcome in mice. Methods C57Bl/6 mice were treated with COU254 (40 mg/kg i.p.) or vehicle and subjected to 60 min transient middle cerebral artery occlusion (tMCAO) using the intraluminal filament method. After 24 h infarct volumes were determined from 2,3,5-Triphenyltetrazoliumchloride(TTC)-stained brain sections and functional scores were assessed. Hematoxylin and eosin (H&amp;E) staining was used to estimate the extent of neuronal cell damage. Thrombus formation within the infarcted brain areas was analyzed by immunoblot. Results Infarct volumes and functional outcomes on day 1 after tMCAO did not significantly differ between COU254 pre-treated mice or untreated controls (p &gt; 0.05). Histology revealed extensive ischemic neuronal damage regularly including the cortex and the basal ganglia in both groups. COU254 treatment did not prevent intracerebral fibrin(ogen) formation. Conclusions COU254 at the given concentration of 40 mg/kg failed to demonstrate efficacy in acute ischemic stroke in this preliminary study. Further preclinical evaluation of 3-carboxamide-coumarins is needed before the antithrombotic potential of this novel class of FXII inhibitors can be finally judged.

Peter Kraft

Tobias Schwarz

Lionel Pochet

Guido Stoll

Christoph Kleinschnitz

COU254, a specific 3-carboxamide-coumarin inhibitor of coagulation factor XII, does not protect mice from acute ischemic stroke

COU254，一种凝血因子XII的特异性3-酰胺香豆素抑制剂，不能保护小鼠免受急性缺血性中风

Transgenic mice bred on C57Bl/6 or Sv/129 genetic background are frequently used in stroke research. It is well established that variations in cerebrovascular anatomy and hemodynamics can influence stroke outcome in different inbred mouse lines. We compared stroke development in C57Bl/6 and Sv/129 mice in the widely used model of transient middle cerebral artery occlusion (tMCAO) by multimodal ultra-high field magnetic resonance imaging (MRI). C57Bl/6 and Sv/129 mice underwent 60 min of tMCAO and were analyzed by MRI 2 h and 24 h afterwards. Structural and functional images were registered to a standard anatomical template. Probability maps of infarction were rendered by automated segmentation from quantitative T2-relaxometric images. Whole-brain segmentation of infarction was accomplished manually on high-resolution T2-weighted (T2-w) RARE images. Cerebral perfusion (cerebral blood flow, CBF) was measured quantitatively by modified continuous arterial-spin-labeling (CASL) and apparent diffusion coefficients (ADC) by spin-echo diffusion-weighted imaging (DWI). Probabilities of cortical (95.1% ± 3.1 vs. 92.1% ± 2.5; p > 0.05) and subcortical (100% vs. 100%; p > 0.05) infarctions at 24 h were similar in both groups as was the whole-brain volumetric extent of cerebral infarction. In addition, CBF and ADC values did not differ between C57Bl/6 and Sv/129 mice at any time point or region of interest. The C57Bl/6 and Sv/129 genetic background is no major confounding factor of infarct size and cerebral perfusion in the tMCAO model.

Mirko Pham

Xavier Helluy

Stefan Braeuninger

Peter Jakob

Martin Bendszus

Outcome of experimental stroke in C57Bl/6 and Sv/129 mice assessed by multimodal ultra-high field MRI

C57Bl/6 和 Sv/129 小鼠实验性卒中的结果通过多模态超高场磁共振成像评估

Report on the 1st scientific meeting of the "Verein zur Forderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Mittenwalde/Motzen, Germany, Oct. 30th - Nov. 1st, 2009. A scientific meeting report.

Tim Magnus

Ralf Linker

Sven G Meuth

Thomas Korn

Report on the 1st scientific meeting of the "Verein zur Förderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Mittenwalde/Motzen, Germany, Oct. 30th - Nov. 1st, 2009

"神经科学青年人才促进协会"（NEUROWIND e.V.）首届科学会议报告，于2009年10月30日至11月1日在德国米滕瓦尔德/莫岑举行

Hypoxia is a common occurrence following stroke and associated with poor clinical and functional outcomes. Normal oxygen physiology is a finely controlled mechanism from the oxygenation of haemoglobin in the pulmonary capillaries to its dissociation and delivery in the tissues. In no organ is this process more important than the brain, which has a number of vascular adaptions to be able to cope with a certain threshold of hypoxia, beyond which further disruption of oxygen delivery potentially leads to devastating consequences. Hypoxia following stroke is common and is often attributed to pneumonia, aspiration and respiratory muscle dysfunction, with sleep apnoea syndromes, pulmonary embolism and cardiac failure being less common but important treatable causes. As well as treating the underlying cause, oxygen therapy is a vital element to correcting hypoxia, but excessive use can itself cause molecular and clinical harm. As cerebral vascular occlusion completely obliterates oxygen delivery to its target tissue, the use of supplemental oxygen, even when not hypoxic, would seem a reasonable solution to try and correct this deficit, but to date randomised clinical trials have not shown benefit. Whilst evidence for the use of supplemental oxygen therapy is currently lacking, it is vital to rapidly identify and treat all causes of hypoxia in the acute stroke patient, as a failure to will lead to poorer clinical outcomes. The full results of a large randomised trial looking at the use of supplemental oxygen therapy are currently pending.

Phillip Ferdinand

Christine Roffe

Hypoxia after stroke: a review of experimental and clinical evidence

卒中后缺氧：实验与临床证据综述

The renin angiotensin system (RAS) consists of the systemic hormone system, critically involved in regulation and homeostasis of normal physiological functions [i.e. blood pressure (BP), blood volume regulation], and an independent brain RAS, which is involved in the regulation of many functions such as memory, central control of BP and metabolic functions. In general terms, the RAS consists of two opposing axes; the 'classical axis' mediated primarily by Angiotensin II (Ang II), and the 'alternative axis' mediated mainly by Angiotensin-(1–7) (Ang-(1–7)). An imbalance of these two opposing axes is thought to exist between genders and is thought to contribute to the pathology of cardiovascular conditions such as hypertension, a stroke co-morbidity. Ischaemic stroke pathophysiology has been shown to be influenced by components of the RAS with specific RAS receptor antagonists and agonists improving outcome in experimental models of stroke. Manipulation of the two opposing axes following acute ischaemic stroke may provide an opportunity for protection of the neurovascular unit, particularly in the presence of pre-existing co-morbidities where the balance may be shifted. In the present review we will give an overview of the experimental stroke studies that have investigated pharmacological interventions of the RAS.

Mariana Moreira Coutinho Arroja

Emma Reid

Christopher McCabe

Therapeutic potential of the renin angiotensin system in ischaemic stroke

缺血性卒中中肾素-血管紧张素系统的治疗潜力

Cerebral hyperperfusion is a relatively rare syndrome with significant and potentially preventable clinical consequences. The pathophysiology of cerebral hyperperfusion syndrome (CHS) may involve dysregulation of the cerebral vascular system and hypertension, in the setting of increase in cerebral blood flow. The early recognition of CHS is important to prevent complications such as intracerebral hemorrhage. This review will focus on CHS following carotid endarterectomy and carotid artery stenting. We will discuss the typical clinical features of CHS, risk factors, pathophysiology, diagnostic modalities for detection, identification of patients at risk, and prevention and treatment. Although currently there are no specific guidelines for the management of CHS, identification of patients at risk for CHS and aggressive treatment of hypertension are recommended.

Muhammad U. Farooq

Christopher Goshgarian

Jiangyong Min

Philip B. Gorelick

Pathophysiology and management of reperfusion injury and hyperperfusion syndrome after carotid endarterectomy and carotid artery stenting

颈动脉内膜切除术和颈动脉支架植入术后再灌注损伤和过度灌注综合征的病理生理学及管理

Suspected transient ischaemic attack (TIA) is a common presentation to emergency medical services (EMS) in the United Kingdom (UK). Several EMS systems have adopted the ABCD2 score to aid pre-hospital risk stratification and decision-making on patient disposition, such as direct referral to an Emergency Department or specialist TIA clinic. However, the ABCD2 score, developed for hospital use, has not been validated for use in the pre-hospital context of EMS care. We conducted a pilot study to assess eligibility criteria, recruitment rates, protocol compliance, consent and follow-up procedures to inform the development of a definitive study to validate the ABCD2 tool in pre-hospital evaluation of patients with suspected TIA. From 1st May–1st September 2013, nine patients with an EMS suspected diagnosis of TIA had the TIA diagnosis later confirmed by a specialist from five participating sites. This recruitment rate is comparable to stroke trials in the EMS setting. Bureaucratic obstacles and duplication of approval processes across participating sites took 13 months to resolve before recruitment commenced. Due to the initial difficulty in recruitment, a substantial amendment was approved to modify inclusion criteria, allowing patients with atrial fibrillation and/or taking anticoagulant therapy to participate in the study. It is possible to identify, recruit and follow up patients with suspected TIA in the EMS setting. Training large numbers of EMS staff is required as exposure to TIA patients is infrequent. Significant insight was gained into the complexity of NHS research governance mechanisms in the UK. This knowledge will facilitate the planning of a future adequately powered study to validate the ABCD2 tool in a pre-hospital setting.

Scott Munro

Sally Rodbard

Khalid Ali

Claire Horsfield

Wendy Knibb

Janet Holah

Ottilia Speirs

Tom Quinn

A pilot study evaluating the use of ABCD2 score in pre-hospital assessment of patients with suspected transient ischaemic attack: experience and lessons learned

一项评估ABCD2评分在疑似短暂性脑缺血发作患者院前评估中应用的初步研究：经验与教训

[This corrects the article DOI: 10.1186/s13231-016-0018-x.].

Ahmed Alhusban

Anna Kozak

Wael Eldahshan

Adviye Ergul

Susan C. Fagan

Erratum to: Artery reopening is required for the neurorestorative effects of angiotensin modulation after experimental stroke

勘误：动脉再通对实验性卒中后血管紧张素调节的神经修复作用是必需的

Publication Information	Publisher: BioMed Central Ltd，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2010，Proportion of original research papers: ，Self Citation Rate:， Gold OA Rate:

Experimental and Translational Stroke Medicine

Journal Citation Format

A journal article with 1 author

A journal article with 2 authors

A journal article with 3 authors

A journal article with 5 or more authors

Books Citation Format

Thesis Citation Format

Web sites Citation Format

Patent Citation Format

Staying up late manually editing references? ivySCI automatically matches journals and helps you generate references with a single click.

Share Submission Experience