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Translational Stroke Research

Arjang Salehi, Amandine Jullienne, Kara M Wendel, Mary Hamer, Jiping Tang, John H Zhang, William J Pearce, Richard A DeFazio, Zinaida S Vexler, Andre Obenaus
We introduce a novel protocol to stain, visualize, and analyze blood vessels from the rat and mouse cerebrum. This technique utilizes the fluorescent dye, DiI, to label the lumen of the vasculature followed by perfusion fixation. Following brain extraction, the labeled vasculature is then imaged using wide-field fluorescence microscopy for axial and coronal images and can be followed by regional confocal microscopy. Axial and coronal images can be analyzed using classical angiographic methods for vessel density, length, and other features...
May 15, 2018: Translational Stroke Research
Ran Liu, Haijiao Li, Ya Hua, Richard F Keep, Jiangxi Xiao, Guohua Xi, Yining Huang
Early hemolysis occurs in the hematoma within 24 h in rat model of intracerebral hemorrhage (ICH). The present study investigated the prevalence of early hemolysis in ICH patients using MRI and the relationship between early hemolysis and perihematomal edema. Thirty ICH patients were prospectively enrolled within 24 h of onset. All patients had cranial CT on admission. Cranial MRI with T2 FLAIR-weighted imaging and T2*-weighted imaging were undertaken at days 1 and 14. The evolution of a non-hypointense lesion on T2*-weighted images and the relationship between the volume of that non-hypointense lesion and perihematomal edema volume were investigated...
May 15, 2018: Translational Stroke Research
Yongqiu Xie, Yi-Ju Li, Beilei Lei, Dawn Kernagis, Wen-Wei Liu, Ellen R Bennett, Talagnair Venkatraman, Christopher D Lascola, Daniel T Laskowitz, David S Warner, Michael L James
Sex dimorphism has been demonstrated after experimental intracerebral hemorrhage (ICH). Decreased mortality and improved neurobehavioral outcomes occur in female compared to male mice after intrastriatal autologous blood or collagenase injection. Sex-specific differences in post-ICH gene and protein expression may provide mechanistic insight into this phenomenon. Ten- to 12-week-old C57BL/6 male (M) and female in high estrous state (HE-F) underwent left intrastriatal collagenase injection. We assessed neurobehavioral outcomes over the first 30 days, hematoma volume and cerebral edema evolution over the first 24 h, and transcriptomic gene and protein expression at pre-selected time points during the acute phase of injury...
May 13, 2018: Translational Stroke Research
Hongyu Xie, Kewei Yu, Naiyun Zhou, Xueyan Shen, Shan Tian, Bei Zhang, Yuyang Wang, Junfa Wu, Gang Liu, Congyu Jiang, Ruiping Hu, Cenk Ayata, Yi Wu
Brain has limited capacity for spontaneous recovery of lost function after stroke. Exposure to enriched environment (EE) can facilitate functional recovery, but mechanisms underlying this effect are poorly understood. Here, we used a middle cerebral artery occlusion (MCAO) model to investigate the impact of EE on angiogenesis in the post-ischemic brain in adult male Sprague Dawley rats, and examined whether blood-borne factors may contribute. Compared with standard cage (SC), exposure to EE was associated with greater improvement in neurological function, higher peri-infarct vascular density, and higher chronic post-ischemic cerebral blood flow assessed by laser speckle imaging...
April 26, 2018: Translational Stroke Research
Maria E Ramos-Araque, Cristina Rodriguez, Rebeca Vecino, Elisa Cortijo Garcia, Mercedes de Lera Alfonso, Mercedes Sanchez Barba, Laura Colàs-Campàs, Francisco Purroy, Juan F Arenillas, Angeles Almeida, Maria Delgado-Esteban
Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2...
April 23, 2018: Translational Stroke Research
Francesco Arba, Benedetta Piccardi, Vanessa Palumbo, Betti Giusti, Patrizia Nencini, Anna Maria Gori, Alice Sereni, Mascia Nesi, Giovanni Pracucci, Giorgio Bono, Paolo Bovi, Enrico Fainardi, Domenico Consoli, Antonia Nucera, Francesca Massaro, Giovanni Orlandi, Francesco Perini, Rossana Tassi, Maria Sessa, Danilo Toni, Rosanna Abbate, Domenico Inzitari
Small vessel disease (SVD) is frequent in aging and stroke patients. Inflammation and remodeling of extracellular matrix have been suggested as concurrent mechanisms of SVD. We investigated the relationship between imaging features of SVD and circulating metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in patients with ischaemic stroke. In patients treated with intravenous thrombolysis, we took blood samples before intravenous thrombolysis and 90 days after the acute stroke and analysed levels of MMPs and TIMPs...
April 23, 2018: Translational Stroke Research
Natasha Shroff, Bradley P Ander, Xinhua Zhan, Boryana Stamova, DaZhi Liu, Heather Hull, Farah R Hamade, Cheryl Dykstra-Aiello, Kwan Ng, Frank R Sharp, Glen C Jickling
The histone deacetylase 9 (HDAC9) polymorphism rs2107595 is associated with an increased risk for large vessel atherosclerotic stroke (LVAS). In humans, there remains a need to better understand this HDAC9 polymorphism's contribution to large vessel stroke. In this pilot study, we evaluated whether the HDAC9 polymorphism rs2107595 is associated with differences in leukocyte gene expression in patients with LVAS. HDAC9 SNP rs2107595 was genotyped in 155 patients (43 LVAS and 112 vascular risk factor controls)...
April 13, 2018: Translational Stroke Research
Gregory J Bix, Justin F Fraser, William J Mack, S Thomas Carmichael, Miguel Perez-Pinzon, Halina Offner, Lauren Sansing, Francesca Bosetti, Cenk Ayata, Keith R Pennypacker
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...
April 10, 2018: Translational Stroke Research
Sarah E Perry, Anna Miles, John N Fink, Maggie-Lee Huckabee
Cough reflex testing has been evaluated as a component of the clinical swallowing assessment as a means of identifying patients at risk of aspiration during swallowing. A previous study by our research group found good sensitivity and specificity of the cough reflex test for identifying patients at risk of aspiration post-stroke, yet its use did not decrease pneumonia rates, contrary to previous reports. The aim of this study was to expand on our earlier work by implementing a clinical management protocol incorporating cough reflex testing within the same healthcare setting and compare patient outcomes to those from the original study and to evaluate clinical outcomes in patients with acute stroke who were managed using the Dysphagia in Stroke Protocol (DiSP)...
March 30, 2018: Translational Stroke Research
James E Faber, Hua Zhang, Wojciech Rzechorzek, Kathy Z Dai, Benjamin T Summers, Cooper Blazek, Samuel J Hedges
Variation in blood flow mediated by the posterior communicating collateral arteries (PComs) contributes to variation in the severity of tissue injury in obstructive disease. Evidence in animals and humans indicates that differences in the extent of PComs, i.e., their anatomic lumen diameter and whether they are present bilaterally, unilaterally, or absent, are a major factor. These differences arise during development since they are present at birth. However, the causal mechanisms are unknown. We used angiography after maximal dilation to examine involvement of genetic, environmental, and stochastic factors...
March 27, 2018: Translational Stroke Research
Motoki Tanaka, Takunori Ogaeri, Mikhail Samsonov, Masahiro Sokabe
Progesterone (P4) exerts potent neuroprotection both in young and aged animal models of stroke. The neuroprotection is likely to be mediated by allopregnanolone (ALLO) metabolized from P4 by 5α-reductase, since the neuroprotection is attenuated by the 5α-reductase inhibitor finasteride, which was done only with young animals though. Thus, we do not know the contribution of ALLO to the P4-induced neuroprotection in aged animals. We examined effects of finasteride on the P4-induced neuroprotection in aged (16-18-month-old) male rats subjected to transient focal cerebral ischemia...
March 25, 2018: Translational Stroke Research
Ye Liu, Emma D Eaton, Taryn E Wills, Sarah K McCann, Ana Antonic, David W Howells
Low translational yield for stroke may reflect the focus of discovery science on rodents rather than humans. Just how little is known about human neuronal ischaemic responses is confirmed by systematic review and meta-analysis revealing that data for the most commonly used SH-SY5Y human cells comprises only 84 papers. Oxygen-glucose deprivation, H2 O2 , hypoxia, glucose-deprivation and glutamate excitotoxicity yielded - 58, - 61, - 29, - 45 and - 49% injury, respectively, with a dose-response relationship found only for H2 O2 injury (R2  = 29...
March 23, 2018: Translational Stroke Research
Bo Chen, Gandi Ng, Yahui Gao, See Wee Low, Edwin Sandanaraj, Boominathan Ramasamy, Sakthivel Sekar, Kishore Bhakoo, Tuck Wah Soong, Bernd Nilius, Carol Tang, Edward G Robins, Julian Goggi, Ping Liao
The transient receptor potential melastatin 4 (TRPM4) channel has been suggested to play a key role in the treatment of ischemic stroke. However, in vivo evaluation of TRPM4 channel, in particular by direct channel suppression, is lacking. In this study, we used multimodal imaging to assess edema formation and quantify the amount of metabolically functional brain salvaged after a rat model of stroke reperfusion. TRPM4 upregulation in endothelium emerges as early as 2 h post-stroke induction. Expression of TRPM4 channel was suppressed directly in vivo by treatment with siRNA; scrambled siRNA was used as a control...
March 22, 2018: Translational Stroke Research
Vibha Shukla, Perry Fuchs, Allen Liu, Charles H Cohan, Chuanhui Dong, Clinton B Wright, Miguel A Perez-Pinzon, Kunjan R Dave
Diabetes significantly increases the risk of stroke and post-stroke mortality. Recurrent hypoglycemia (RH) is common among diabetes patients owing to glucose-lowering therapies. Earlier, we showed that RH in a rat model of insulin-dependent diabetes exacerbates cerebral ischemic damage. Impaired mitochondrial function has been implicated as a central player in the development of cerebral ischemic damage. Hypoglycemia is also known to affect mitochondrial functioning. The present study tested the hypothesis that prior exposure of insulin-treated diabetic (ITD) rats to RH exacerbates brain damage via enhanced post-ischemic mitochondrial dysfunction...
March 22, 2018: Translational Stroke Research
Grant C O'Connell, Madison B Treadway, Connie S Tennant, Noelle Lucke-Wold, Paul D Chantler, Taura L Barr
Our group recently identified a panel of ten genes whose RNA expression levels in whole blood have utility for detection of stroke. The purpose of this study was to determine the mechanisms by which these genes become differentially expressed during stroke pathology. First, we assessed the transcriptional distribution of the ten genes across the peripheral immune system by measuring their expression levels on isolated neutrophils, monocytes, B-lymphocytes, CD-4+ T-lymphocytes, CD-8+ T-lymphocytes, and NK-cells generated from the blood of healthy donors (n = 3)...
March 17, 2018: Translational Stroke Research
Saadat Kamran, Abdul Salam, Naveed Akhtar, Ayman Alboudi, Kainat Kamran, Rajvir Singh, Numan Amir, Jihad Inshasi, Uwais Qidwai, Rayaz A Malik, Ashfaq Shuaib
In patients with malignant middle cerebral artery (MMCA) stroke, a vital clinically relevant question is determination of the speed with which infarction evolves to select the time for decompressive hemicraniectomy [DHC]. A retrospective, multicenter cross-sectional study of patients referred for DHC, based on the criteria of randomized controlled trials, was undertaken to identify factors for selecting the timing of DHC in MMCA stroke, stratified by time [< 48, 48-72, > 72 h]. Infarction volume and infarct growth rate [IGR] were measured on all CT scans...
March 6, 2018: Translational Stroke Research
Tomáš Dorňák, Michal Král, Zuzana Sedláčková, Daniel Šaňák, Eva Čecháková, Petra Divišová, Jana Zapletalová, Petr Kaňovský
In the original publication of the article, there was a switched order of author names.
March 5, 2018: Translational Stroke Research
Lin Liu, Hui Yuan, Yanhua Yi, Edward C Koellhoffer, Yashasvee Munshi, Fan Bu, Yi Zhang, Zhenggang Zhang, Louise D McCullough, Jun Li
Neurite plasticity is a critical aspect of brain functional recovery after stroke. Emerging data suggest that Ras-related C3 botulinum toxin substrate 1 (Rac1) plays a central role in axonal regeneration in the injured brain, specifically by stimulating neuronal intrinsic growth and counteracting the growth inhibitory signaling that leads to growth cone collapse. Therefore, we investigated the functional role of Rac1 in axonal regeneration after stroke.Delayed treatment with a specific Rac1 inhibitor, NSC 23766, worsened functional recovery, which was assessed by the pellet reaching test from day 14 to day 28 after stroke...
February 24, 2018: Translational Stroke Research
William M Armstead, Hugh Hekierski, Philip Pastor, Serge Yarovoi, Abd Al-Roof Higazi, Douglas B Cines
The sole FDA-approved drug treatment for ischemic stroke is tissue-type plasminogen activator (tPA). However, upregulation of JNK mitogen-activated protein kinase (MAPK) and endothelin 1 (ET-1) by tPA after stroke contributes to impaired cerebrovascular autoregulation. Wild-type (wt) tPA can bind to the lipoprotein-related receptor (LRP), which mediates vasodilation, or NMDA receptors (NMDA-Rs), exacerbating vasoconstriction. Elevations in IL-6, a marker of inflammation that accompanies stroke, are reported to be an adverse prognostic factor...
February 23, 2018: Translational Stroke Research
Devin William McBride, Guangyong Wu, Derek Nowrangi, Jerry J Flores, Liang Hui, Paul R Krafft, John H Zhang
Most large vessel stroke patients have permanent occlusion, for which there are no current treatment options. Recent case studies have indicated delayed recanalization, that is recanalization outside of the 6-h treatment window, may lead to improved outcome. We hypothesized that delayed recanalization will restore cerebral blood flow, leading to improved function in rats. Male SD rats were subjected to pMCAO or sham surgery. Delayed recanalization was performed on either day 3, 7, or 14 after pMCAO in a subset of animals...
April 2018: Translational Stroke Research
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