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Experimental & Translational Stroke Medicine

Phillip Ferdinand, Christine Roffe
BACKGROUND: 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...
2016: Experimental & Translational Stroke Medicine
Mariana Moreira Coutinho Arroja, Emma Reid, Christopher McCabe
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))...
2016: Experimental & Translational Stroke Medicine
Muhammad U Farooq, Christopher Goshgarian, Jiangyong Min, Philip B Gorelick
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...
2016: Experimental & Translational Stroke Medicine
Scott Munro, Sally Rodbard, Khalid Ali, Claire Horsfield, Wendy Knibb, Janet Holah, Ottilia Speirs, Tom Quinn
BACKGROUND: 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. METHODS: 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...
2016: Experimental & Translational Stroke Medicine
Ahmed Alhusban, Anna Kozak, Wael Eldahshan, Adviye Ergul, Susan C Fagan
[This corrects the article DOI: 10.1186/s13231-016-0018-x.].
2016: Experimental & Translational Stroke Medicine
Ahmed Alhusban, Anna Kozak, Wael Eldashan, Adviye Ergul, Susan C Fagan
BACKGROUND: Blood flow restoration with fibrinolysis and thrombectomy is recommended to limit injury in stroke patients with proximal artery occlusion. Angiotensin receptor blockers have been shown to be neuroprotective in models of permanent and temporary occlusion, but the benefits on expression of trophic factors have been seen only when the artery is reopened. It is possible that early artery opening with endovascular intervention may increase the likelihood of identifying an effective combination therapy for patients...
2016: Experimental & Translational Stroke Medicine
Elisa Cuccione, Giada Padovano, Alessandro Versace, Carlo Ferrarese, Simone Beretta
Cerebral collateral circulation is a subsidiary vascular network, which is dynamically recruited after arterial occlusion, and represents a powerful determinant of ischemic stroke outcome. Although several methods may be used for assessing cerebral collaterals in the acute phase of ischemic stroke in humans and rodents, they are generally underutilized. Experimental stroke models may play a unique role in understanding the adaptive response of cerebral collaterals during ischemia and their potential for therapeutic modulation...
2016: Experimental & Translational Stroke Medicine
Frieder Schlunk, Waltraud Pfeilschifter, Kazim Yigitkanli, Eng H Lo, Christian Foerch
BACKGROUND: No evidence-based therapy is available for patients with acute intracerebral hemorrhage (ICH). In view of the profound inflammatory reaction in the perilesional tissue, we investigated in a well-characterized experimental model whether the administration of the immunomodulator fingolimod (FTY720) is neuroprotective in acute ICH. METHODS: ICH was induced by means of a stereotactic intrastriatal injection of collagenase type VII-S. FTY720 (1 mg/kg) was administered intraperitoneally 1 h after ICH induction...
2016: Experimental & Translational Stroke Medicine
Christoph Kleinschnitz, Ralf A Linker, Tim Magnus, Thomas Korn, Sven G Meuth
From October 31th - November 2nd, 2014, the 6th NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. 70 doctoral students and postdocs from over 25 different groups working in German and Swiss university hospitals or research institutes attended the meeting to discuss their latest experiments and findings in the fields of neuroimmunology, neurodegeneration and neurovascular research. The meeting was regarded as a very well organized platform to support research of young investigators in Germany and all participants enjoyed the stimulating environment for lively in depth discussions...
2015: Experimental & Translational Stroke Medicine
Amelia J Tomkins, Nadine Schleicher, Lucy Murtha, Manfred Kaps, Christopher R Levi, Max Nedelmann, Neil J Spratt
BACKGROUND: Early recanalization of occluded vessels in stroke is closely associated with improved clinical outcome. Microbubble-enhanced sonothrombolysis is a promising therapy to improve recanalization rates and reduce the time to recanalization. Testing any thrombolytic therapy requires a model of thromboembolic stroke, but to date these models have been highly variable with regards to clot stability. Here, we developed a model of thromboembolic stroke in rats with site-specific delivery of platelet-rich clots (PRC) to the main stem of the middle cerebral artery (MCA)...
2015: Experimental & Translational Stroke Medicine
Sung-Ha Hong, Larissa Khoutorova, Nicolas G Bazan, Ludmila Belayev
BACKGROUND: Ischemic brain injury disrupts the blood-brain barrier (BBB) and then triggers a cascade of events, leading to edema formation, secondary brain injury and poor neurological outcomes. Recently, we have shown that docosahexaenoic acid (DHA) improves functional and histological outcomes following experimental stroke. However, little is known about the effect of DHA on BBB dysfunction after cerebral ischemia-reperfusion injury. The present study was designed to determine whether DHA protects against BBB disruption after focal cerebral ischemia in rats...
2015: Experimental & Translational Stroke Medicine
Simon R Platt, Shannon P Holmes, Elizabeth W Howerth, Kylee Jo J Duberstein, C Robert Dove, Holly A Kinder, Emily L Wyatt, Amie V Linville, Vivian W Lau, Steven L Stice, William D Hill, David C Hess, Franklin D West
BACKGROUND: Efforts to develop stroke treatments have met with limited success despite an intense need to produce novel treatments. The failed translation of many of these therapies in clinical trials has lead to a close examination of the therapeutic development process. One of the major factors believed to be limiting effective screening of these treatments is the absence of an animal model more predictive of human responses to treatments. The pig may potentially fill this gap with a gyrencephalic brain that is larger in size with a more similar gray-white matter composition to humans than traditional stroke animal models...
March 23, 2014: Experimental & Translational Stroke Medicine
Peter Kraft, Kerstin Göbel, Sven G Meuth, Christoph Kleinschnitz
BACKGROUND: The role of the immune system in the pathophysiology of acute ischemic stroke is increasingly recognized. However, targeted treatment strategies to modulate immunological pathways in stroke are still lacking. Glatiramer acetate is a multifaceted immunomodulator approved for the treatment of relapsing-remitting multiple sclerosis. Experimental studies suggest that glatiramer acetate might also work in other neuroinflammatory or neurodegenerative diseases apart from multiple sclerosis...
February 27, 2014: Experimental & Translational Stroke Medicine
Armin Schneider, Andreas Rogalewski, Oliver Wafzig, Friederike Kirsch, Norbert Gretz, Carola Krüger, Kai Diederich, Claudia Pitzer, Rico Laage, Christian Plaas, Gerhard Vogt, Jens Minnerup, Wolf-Rüdiger Schäbitz
BACKGROUND AND PURPOSE: Both the immobilization of the unaffected arm combined with physical therapy (forced arm use, FAU) and voluntary exercise (VE) as model for enriched environment are promising approaches to enhance recovery after stroke. The genomic mechanisms involved in long-term plasticity changes after different means of rehabilitative training post-stroke are largely unexplored. The present investigation explored the effects of these physical therapies on behavioral recovery and molecular markers of regeneration after experimental ischemia...
February 14, 2014: Experimental & Translational Stroke Medicine
Claudia Pösel, Anna Uri, Isabell Schulz, Johannes Boltze, Gesa Weise, Daniel-Christoph Wagner
BACKGROUND: Sterile inflammation is a substantial element of post-stroke pathophysiology with the determination of autoimmunity versus tolerance being one of its most important aspects. It is believed that this determination is initiated relatively early after stroke onset by clearing macrophages and migratory dendritic cells (DC). However, the phenotypic differentiation of macrophages and DC is intricate particularly in the disease context. Here, we utilized a set of surface markers used in mucosal immunity research to investigate the involvement of macrophages and DC subpopulations in post-stroke inflammation in mice...
2014: Experimental & Translational Stroke Medicine
Md Nasrul Hoda, Susan C Fagan, Mohammad B Khan, Kumar Vaibhav, Aizaz Chaudhary, Phillip Wang, Krishnan M Dhandapani, Jennifer L Waller, David C Hess
BACKGROUND: After the failure of so many drugs and therapies for acute ischemic stroke, innovative approaches are needed to develop new treatments. One promising strategy is to test combinations of agents in the pre-hospital setting prior to the administration of intravenous tissue plasminogen activator (IV-tPA) and/ or the use of mechanical reperfusion devices in the hospital. METHODS: We performed a 2 × 2 factorial design preclinical trial where we tested minocycline (MINO), remote ischemic perconditioning (RIPerC) and their combination treatment in a thromboembolic clot model of stroke in mice, without IV-tPA or later treated with IV-tPA at 4 hours post-stroke...
2014: Experimental & Translational Stroke Medicine
Fanny Quandt, Friedhelm C Hummel
Neuromuscular stimulation has been used as one potential rehabilitative treatment option to restore motor function and improve recovery in patients with paresis. Especially stroke patients who often regain only limited hand function would greatly benefit from a therapy that enhances recovery and restores movement. Multiple studies investigated the effect of functional electrical stimulation on hand paresis, the results however are inconsistent. Here we review the current literature on functional electrical stimulation on hand motor recovery in stroke patients...
2014: Experimental & Translational Stroke Medicine
Kathleen M Buckley, Daniel L Hess, Irina Y Sazonova, Sudharsan Periyasamy-Thandavan, John R Barrett, Russell Kirks, Harrison Grace, Galina Kondrikova, Maribeth H Johnson, David C Hess, Patricia V Schoenlein, Md Nasrul Hoda, William D Hill
BACKGROUND AND PURPOSE: The role of autophagy in response to ischemic stroke has been confusing with reports that both enhancement and inhibition of autophagy decrease infarct size and improve post-stroke outcomes. We sought to clarify this by comparing pharmacologic modulation of autophagy in two clinically relevant murine models of stroke. METHODS: We used rapamycin to induce autophagy, and chloroquine to block completion of autophagy, by treating mice immediately after stroke and at 24 hours post-stroke in two different models; permanent Middle Cerebral Artery Ligation (MCAL), which does not allow for reperfusion of distal trunk of middle cerebral artery, and Embolic Clot Middle Cerebral Artery Occlusion (eMCAO) which allows for a slow reperfusion similar to that seen in most human stroke patients...
2014: Experimental & Translational Stroke Medicine
Alexander Widiapradja, Tomislav Santro, Milan Basta, Christopher G Sobey, Silvia Manzanero, Thiruma V Arumugam
BACKGROUND: The brain endothelium is a key component of the blood brain barrier which is compromised following ischemia, allowing infiltration of damaging immune cells and other inflammatory molecules into the brain. Intravenous immunoglobulin (IVIg) is known to reduce infarct size in a mouse model of experimental stroke. FINDINGS: Flow cytometry analysis showed that the protective effect of IVIg in ischemia and reperfusion injury in vivo is associated with reduced leukocyte infiltration, suggesting an involvement of the endothelium...
2014: Experimental & Translational Stroke Medicine
Aslan Güzel, Roland Rölz, Guido Nikkhah, Ulf D Kahlert, Jaroslaw Maciaczyk
INTRODUCTION: Although there are many experimental studies describing the methodology of the middle cerebral artery occlusion (MCAO) in the literature, only limited data on these distinct anatomical structures and the details of the surgical procedure in a step by step manner. The aim of the present study simply is to examine the surgical anatomy of MCAO model and its modifications in the rat. MATERIALS AND METHODS: Forty Sprague-Dawley rats were used; 20 during the training phase and 20 for the main study...
2014: Experimental & Translational Stroke Medicine
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