http://www.etsmjournal.com The most accessed research articles published by Experimental & Translational Stroke Medicine 2012-05-03T00:00:00Z Background: Since several neuroprotectives failed to reproduce promising preclinical results under clinicalconditions, efforts emerged to implement clinically relevant endpoints in animal strokestudies. Thereby, insufficient attention was given on autonomic reactions due to experimentalstroke, although clinical trials reported on high functional and prognostic impact. This studyfocused on autonomic consequences and body weight changes in a translational relevantstroke model and investigated interrelations to different outcome measurements. Methods: Forty-eight rats underwent thromboembolic middle cerebral artery occlusion (MCAO) whilerecording heart rate (HR) and mean arterial pressure (MAP). After assessing early functionalimpairment (Menzies score), animals were assigned to control procedure or potentiallyneuroprotective treatment with normobaric (NBO) or hyperbaric oxygen (HBO). Four or 24hours after ischemia onset, functional impairment was re-assessed and FITC-albuminadministered intravenously obtaining leakage-related blood-brain barrier (BBB) impairment.Body weight was documented prior to MCAO and 4 or 24 hours after ischemia onset. Results: During MCAO, HR was found to increase significantly while MAP decreased. The amountof changes in HR was positively correlated with early functional impairment (P = 0.001):Severely affected animals provided an increase of 15.2 compared to 0.8 beats/minute in ratswith low impairment (P = 0.048). Regarding body weight, a decrease of 9.4% within 24hours after MCAO occurred, but treatment-specific alterations showed no significantcorrelations with respective functional or BBB impairment. Conclusions: Future studies should routinely include autonomic parameters to allow inter-groupcomparisons and better understanding of autonomic reactions due to experimental stroke.Prospectively, autonomic consequences might represent a useful outcome parameterenhancing the methodological spectrum of preclinical stroke studies. http://www.etsmjournal.com/content/4/1/7 Dominik Michalski Christopher Weise Carsten Hobohm Lea Küppers-Tiedt Johann Pelz Dietmar Schneider Johannes Kacza Wolfgang Härtig Experimental & Translational Stroke Medicine 2012, null:7 2012-04-17T00:00:00Z doi:10.1186/2040-7378-4-7 /content/figures/2040-7378-4-7-toc.gif Experimental & Translational Stroke Medicine 2040-7378 ${item.volume} 7 2012-04-17T00:00:00Z PDF Background: Rapid reperfusion following ischemia is the most effective therapy in stroke therapy.However, the success may be compromised by ischemia & reperfusion (I/R) injury and at thehuman blood-brain barrier (BBB), therefore the effects on transendothelial transport are ofspecial interest. Current studies suggest the ATP-binding cassette (ABC) transporters to beregulated upon ischemic stroke in a way that impedes the effects of drug therapy. Theimmortalised human brain microvascular endothelial cell line hCMEC/day provides most ofthe unique properties of the BBB with respect to transport and might be a reliable in vitromodel to study transendothelial transport after I/R. Methods: We exposed hCMEC/D3 cells to 24 hours of hypoxia alone and to hypoxia followed by 60min of reoxygenisation as a in vitro model for I/R. Western blot showed mild upregulation ofhypoxia inducible factor (HIF-1alpha) after hypoxia alone and RNA lysates were analysed with awell-established real-time RT-PCR-based TaqMan low-density array detecting 47 of 48known human ABC transporters. Results: No significant increases of ABC mRNA expression levels were detected neither in hypoxicnor in I/R samples. However, slight decrease of ABCC1 in hypoxic and I/R samples and ofABCA10 and ABCD3 in I/R samples was observed. Conclusion: Our data suggests that hCMEC/D3 cell line and - at the moment - in vitro models in generalare a poor basis for stroke research but may be enhanced by co-culturing more cells of theneurovascular unit inducing an overall ischemic response at the BBB. http://www.etsmjournal.com/content/4/1/9 Christian Lindner Alexander Sigrüner Franziska Walther Ulrich Bogdahn Pierre Couraud Gert Schmitz Felix Schlachetzki Experimental & Translational Stroke Medicine 2012, null:9 2012-05-03T00:00:00Z doi:10.1186/2040-7378-4-9 /content/figures/2040-7378-4-9-toc.gif Experimental & Translational Stroke Medicine 2040-7378 ${item.volume} 9 2012-05-03T00:00:00Z PDF Background: Activation of adenosine A1 receptors has neuroprotective effects in animal stroke models. Adenosine levels are regulated by nucleoside transporters. In vitro studies showed that neuron-specific expression of human equilibrative nucleoside transporter 1 (hENT1) decreases extracellular adenosine levels and adenosine A1 receptor activity. In this study, we tested the effect of hENT1 expression on cortical infarct size following intracerebral injection of the vasoconstrictor endothelin-1 (ET-1) or saline. Methods: Mice underwent stereotaxic intracortical injection of ET-1 (1 μl; 400 pmol) or saline (1 μl). Some mice received the adenosine receptor antagonist caffeine (25 mg/kg, intraperitoneal) 30 minutes prior to ET-1. Perfusion and T2-weighted magnetic resonance imaging (MRI) were used to measure cerebral blood flow (CBF) and subsequent infarct size, respectively. Results: ET-1 reduced CBF at the injection site to 7.3 ± 1.3% (n = 12) in hENT1 transgenic (Tg) and 12.5 ± 2.0% (n = 13) in wild type (Wt) mice. At 48 hours following ET-1 injection, CBF was partially restored to 35.8 ± 4.5% in Tg and to 45.2 ± 6.3% in Wt mice; infarct sizes were significantly greater in Tg (9 ± 1.1 mm3) than Wt (5.4 ± 0.8 mm3) mice. Saline-treated Tg and Wt mice had modest decreases in CBF and infarcts were less than 1 mm3. For mice treated with caffeine, CBF values and infarct sizes were not significantly different between Tg and Wt mice. Conclusions: ET-1 produced greater ischemic injury in hENT1 Tg than in Wt mice. This genotype difference was not observed in mice that had received caffeine. These data indicate that hENT1 Tg mice have reduced ischemia-evoked increases in adenosine receptor activity compared to Wt mice. http://www.etsmjournal.com/content/4/1/4 Hanifi Soylu Dali Zhang Richard Buist Melanie Martin Benedict Albensi Fiona Parkinson Experimental & Translational Stroke Medicine 2012, null:4 2012-03-12T00:00:00Z doi:10.1186/2040-7378-4-4 /content/figures/2040-7378-4-4-toc.gif Experimental & Translational Stroke Medicine 2040-7378 ${item.volume} 4 2012-03-12T00:00:00Z XML Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury. http://www.etsmjournal.com/content/2/1/16 Christiane Albert-Weissenberger Anna-Leena Siren Experimental & Translational Stroke Medicine 2010, null:16 2010-08-13T00:00:00Z doi:10.1186/2040-7378-2-16 /content/figures/2040-7378-2-16-toc.gif Experimental & Translational Stroke Medicine 2040-7378 ${item.volume} 16 2010-08-13T00:00:00Z XML Stroke is a common cause of permanent disability accompanied by devastating impairments for which there is a pressing need for effective treatment. Motor, sensory and cognitive deficits are common following stroke, yet treatment is limited. Along with histological measures, functional outcome in animal models has provided valuable insight to the biological basis and potential rehabilitation efforts of experimental stroke. Developing and using tests that have the ability to identify behavioral deficits is essential to expanding the development of translational therapies. The present aim of this paper is to review many of the current behavioral tests that assess functional outcome after stoke in rodent models. While there is no perfect test, there are many assessments that are sensitive to detecting the array of impairments, from global to modality specific, after stroke. http://www.etsmjournal.com/content/2/1/13 Krystal Schaar Miranda Brenneman Sean Savitz Experimental & Translational Stroke Medicine 2010, null:13 2010-07-19T00:00:00Z doi:10.1186/2040-7378-2-13 /content/figures/2040-7378-2-13-toc.gif Experimental & Translational Stroke Medicine 2040-7378 ${item.volume} 13 2010-07-19T00:00:00Z XML Stroke is a leading cause of disability and death in many countries. Understanding the pathophysiology of ischemic injury and developing therapies is an important endeavor that requires much additional research. Animal stroke models provide an important mechanism for these activities. A large number of stroke models have been developed and are currently used in laboratories around the world. These models are overviewed as are approaches for measuring infarct size and functional outcome. http://www.etsmjournal.com/content/1/1/7 Kenneth Sicard Marc Fisher Experimental & Translational Stroke Medicine 2009, null:7 2009-11-13T00:00:00Z doi:10.1186/2040-7378-1-7 /content/figures/2040-7378-1-7-toc.gif Experimental & Translational Stroke Medicine 2040-7378 ${item.volume} 7 2009-11-13T00:00:00Z XML Stroke, a major cause of disability and mortality in the elderly, occurs when a cerebral blood vessel is occluded or ruptured, resulting in ischemic damage and death of brain cells. The injury mechanism involves metabolic and oxidative stress, excitotoxicity, apoptosis and inflammatory processes, including activation of glial cells and infiltration of leukocytes. In animal models, dietary energy restriction, by daily calorie reduction (CR) or intermittent fasting (IF), extends lifespan and decreases the development of age-related diseases. Dietary energy restriction may also benefit neurons, as suggested by experimental evidence showing that CR and IF protect neurons against degeneration in animal models. Recent findings by our group and others suggest the possibility that dietary energy restriction may protect against stroke induced brain injury, in part by inducing the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF); protein chaperones, including heat shock protein 70 (Hsp70) and glucose regulated protein 78 (GRP78); antioxidant enzymes, such as superoxide dismutases (SOD) and heme oxygenase-1 (HO-1), silent information regulator T1 (SIRT1), uncoupling proteins and anti-inflammatory cytokines. This article discusses the protective mechanisms activated by dietary energy restriction in ischemic stroke. http://www.etsmjournal.com/content/3/1/8 Silvia Manzanero Mathias Gelderblom Tim Magnus Thiruma Arumugam Experimental & Translational Stroke Medicine 2011, null:8 2011-09-12T00:00:00Z doi:10.1186/2040-7378-3-8 /content/figures/2040-7378-3-8-toc.gif Experimental & Translational Stroke Medicine 2040-7378 ${item.volume} 8 2011-09-12T00:00:00Z XML Rodent models of focal cerebral ischemia are essential tools in experimental stroke research. They have added tremendously to our understanding of injury mechanisms in stroke and have helped to identify potential therapeutic targets. A plethora of substances, however, in particular an overwhelming number of putative neuroprotective agents, have been shown to be effective in preclinical stroke research, but have failed in clinical trials. A lot of factors may have contributed to this failure of translation from bench to bedside. Often, deficits in the quality of experimental stroke research seem to be involved. In this article, we review the commonest rodent models of focal cerebral ischemia - middle cerebral artery occlusion, photothrombosis, and embolic stroke models - with their respective advantages and problems, and we address the issue of quality in preclinical stroke modeling as well as potential reasons for translational failure. http://www.etsmjournal.com/content/1/1/8 Stefan Braeuninger Christoph Kleinschnitz Experimental & Translational Stroke Medicine 2009, null:8 2009-11-25T00:00:00Z doi:10.1186/2040-7378-1-8 /content/figures/2040-7378-1-8-toc.gif Experimental & Translational Stroke Medicine 2040-7378 ${item.volume} 8 2009-11-25T00:00:00Z XML The method to induce unilateral cryogenic lesions was first described in 1958 by Klatzo. We describe here an adaptation of this model that allows reliable measurement of lesion volume and vasogenic edema by 2, 3, 5-triphenyltetrazolium chloride (TTC) -staining and Evans blue extravasation in mice. A copper or aluminium cylinder with a tip diameter of 2.5 mm is cooled with liquid nitrogen (-196degreesC) and placed on the exposed skull bone over the parietal cortex (stereotaxic coordinates from bregma: 1.5 mm posterior, 1.5 mm lateral). The tip diameter and the contact time between the tip and the parietal skull determine the extent of cryolesion. Due to an early damage of the blood brain barrier (BBB), the cryogenic cortical injury is characterized by vasogenic edema, marked brain swelling, and inflammation. The lesion grows during the first 24 hours, a process involving complex interactions between endothelial cells, immune cells, cerebral blood flow, and the intracranial pressure. These contribute substantially to the damage from the initial injury. The major advantage of the cryogenic lesion model is the circumscribed and highly reproducible lesion size and location. http://www.etsmjournal.com/content/4/1/6 Furat Raslan Christiane Albert-WeiSZenberger Ralf-Ingo Ernestus Christoph Kleinschnitz Anna-Leena Siren Experimental & Translational Stroke Medicine 2012, null:6 2012-04-05T00:00:00Z doi:10.1186/2040-7378-4-6 /content/figures/2040-7378-4-6-toc.gif Experimental & Translational Stroke Medicine 2040-7378 ${item.volume} 6 2012-04-05T00:00:00Z PDF Background: Severe brain edema is observed in a number of patients suffering from subarachnoidhemorrhage (SAH). Little is known about its pathogenesis and time-course in the first hoursafter SAH. This study was performed to investigate the development of brain edema and itscorrelation with brain perfusion after experimental SAH. Methods: Male Sprague-Dawley rats, randomly assigned to one of six groups (n = 8), were subjected toSAH using the endovascular filament model or underwent a sham operation. Animals weresacrificed 15, 30, 60, 180 or 360 minutes after SAH. Intracranial pressure (ICP), meanarterial blood pressure (MABP), cerebral perfusion pressure (CPP) and bilateral local cerebralblood flow (LCBF) were continuously measured. Brain water content (BWC) was determinedby the wet/dry-weight method. Results: After SAH, CPP and LCBF rapidly decreased. The decline of LCBF markedly exceeded thedecline of CPP and persisted until the end of the observation period. BWC continuouslyincreased. A significant correlation was observed between the BWC and the extent of theperfusion deficit in animals sacrificed after 180 and 360 minutes. Conclusions: The significant correlation with the perfusion deficit after SAH suggests that the developmentof brain edema is related to the extent of ischemia and acute vasoconstriction in the firsthours after SAH. http://www.etsmjournal.com/content/4/1/8 Thomas Westermaier Christian Stetter Furat Raslan Giles Hamilton Vince Ralf-Ingo Ernestus Experimental & Translational Stroke Medicine 2012, null:8 2012-05-02T00:00:00Z doi:10.1186/2040-7378-4-8 /content/figures/2040-7378-4-8-toc.gif Experimental & Translational Stroke Medicine 2040-7378 ${item.volume} 8 2012-05-02T00:00:00Z PDF