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Translational Stroke Research

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https://www.readbyqxmd.com/read/29150739/cell-therapy-in-stroke-cautious-steps-towards-a-clinical-treatment
#1
REVIEW
Olivier Detante, Keith Muir, Jukka Jolkkonen
In the future, stroke patients may receive stem cell therapy as this has the potential to restore lost functions. However, the development of clinically deliverable therapy has been slower and more challenging than expected. Despite recommendations by STAIR and STEPS consortiums, there remain flaws in experimental studies such as lack of animals with comorbidities, inconsistent approaches to experimental design, and concurrent rehabilitation that might lead to a bias towards positive results. Clinical studies have typically been small, lacking control groups as well as often without clear biological hypotheses to guide patient selection...
November 17, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29127592/disease-of-mrna-regulation-relevance-for-ischemic-brain-injury
#2
Donald J DeGracia
In this mini-review we give an overview of the role of mRNA-binding proteins and their associated messenger ribonucleoprotein complexes (mRNPs) in several disease states, and bring this information to bear on the pathophysiology of brain ischemia. One conclusion reached is that mRNPs may play a causal role in proteotoxicity instead of being merely passive targets. Ischemia therapies targeting mRNPs have advantages over targeting single pathways, but the behavior of mRNPs needs to be considered in the design of therapies...
November 10, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29119370/vasoconstriction-and-impairment-of-neurovascular-coupling-after-subarachnoid-hemorrhage-a-descriptive-analysis-of-retinal-changes
#3
Catharina Conzen, Walid Albanna, Miriam Weiss, David Kürten, Walthard Vilser, Konstantin Kotliar, Charlotte Zäske, Hans Clusmann, Gerrit Alexander Schubert
Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5-14), in 11 patients 3 months after ictus (group B: day 90 ± 35), and in 35 age-matched healthy controls (group C)...
November 8, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29119369/clinical-importance-of-temporal-bone-features-for-the-efficacy-of-contrast-enhanced-sonothrombolysis-a-retrospective-analysis-of-the-nor-sass-trial
#4
Vojtech Novotny, Aliona Nacu, Christopher E Kvistad, Annette Fromm, Gesche F Neckelmann, Andrej N Khanevski, Haakon Tobro, Ulrike Waje-Andreassen, Halvor Naess, Lars Thomassen, Nicola Logallo
Contrast-enhanced sonothrombolysis (CEST) seems to be a safe and promising treatment in acute ischemic stroke. It remains unknown if temporal bone features may influence the efficacy of CEST. We investigated the association between different temporal bone features on admission computed tomography (CT) scan and the outcome in acute ischemic stroke patients included in the randomized Norwegian Sonothrombolysis in Acute Stroke Study (NOR-SASS). Patients diagnosed as stroke mimics and those with infratentorial stroke or with incorrect insonation were excluded...
November 8, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29116527/worse-outcome-in-stroke-patients-treated-with-rt-pa-without-early-reperfusion-associated-factors
#5
Ramón Iglesias-Rey, Manuel Rodríguez-Yáñez, Emilio Rodríguez-Castro, José Manuel Pumar, Susana Arias, María Santamaría, Iria López-Dequidt, Pablo Hervella, Clara Correa-Paz, Tomás Sobrino, Denis Vivien, Francisco Campos, Mar Castellanos, José Castillo
Based on preclinical studies suggesting that recombinant tissue plasminogen activator (rt-PA) may promote ischemic brain injuries, we investigated in patients the possible risk of worse clinical outcome after rt-PA treatment as a result of its inability to resolve cerebral ischemia. Here, we designed a cohort study using a retrospective analysis of patients who received treatment with intravenous (4.5-h window) or intraarterial rt-PA, without or with thrombectomy. Controls were consecutive patients who did not receive recanalization treatment, who met all inclusion criteria...
November 7, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29110250/treatment-with-the-ppar%C3%AE-agonist-pioglitazone-in-the-early-post-ischemia-phase-inhibits-pro-inflammatory-responses-and-promotes-neurogenesis-via-the-activation-of-innate-and-bone-marrow-derived-stem-cells-in-rats
#6
Tomoya Kinouchi, Kenji Shimada, Kenji Yagi, Yoshiteru Tada, Nobuhisa Matsushita, Yoshitaka Kurashiki, Junichiro Satomi, Masataka Sata, Shinji Nagahiro
Neurogenesis is essential for a good post-stroke outcome. Exogenous stem cells are currently being tested to promote neurogenesis after stroke. Elsewhere, we demonstrated that treatment with the PPARγ agonist pioglitazone (PGZ) before cerebral ischemia induction reduced brain damage and activated survival-related genes in ovariectomized (OVX) rats. Here, we tested our hypothesis that post-ischemia treatment with PGZ inhibits brain damage and contributes to neurogenesis via activated stem cells. Bone marrow (BM) cells of 7-week-old Wistar female rats were replaced with BM cells from green fluorescent protein-transgenic (GFP(+BM)) rats...
November 6, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29103103/heroin-use-is-associated-with-ruptured-saccular-aneurysms
#7
Anil Can, Victor M Castro, Yildirim H Ozdemir, Sarajune Dagen, Dmitriy Dligach, Sean Finan, Sheng Yu, Vivian Gainer, Nancy A Shadick, Guergana Savova, Shawn Murphy, Tianxi Cai, Scott T Weiss, Rose Du
While cocaine use is thought to be associated with aneurysmal rupture, it is not known whether heroin use increases the risk of rupture in patients with non-mycotic saccular aneurysms. Our goal was to investigate the association between heroin and cocaine use and the rupture of saccular non-mycotic aneurysms. The medical records of 4701 patients with 6411 intracranial aneurysms, including 1201 prospective patients, diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016 were reviewed and analyzed...
November 4, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29103102/combination-of-emricasan-with-ponatinib-synergistically-reduces-ischemia-reperfusion-injury-in-rat-brain-through-simultaneous-prevention-of-apoptosis-and-necroptosis
#8
Jing Tian, Shu Guo, Heng Chen, Jing-Jie Peng, Miao-Miao Jia, Nian-Sheng Li, Xiao-Jie Zhang, Jie Yang, Xiu-Ju Luo, Jun Peng
Apoptosis and receptor-interacting protein kinase 1/3(RIPK1/3)-mediated necroptosis contribute to the cerebral ischemia/reperfusion (I/R) injury. Emricasan is an inhibitor of caspases in clinical trials for liver diseases while ponatinib could be a potential inhibitor for RIPK1/3. This study aims to investigate the effect of emricasan and/or ponatinib on cerebral I/R injury and the underlying mechanisms. Firstly, we evaluated the status of apoptosis and necroposis in a rat model of cerebral I/R under different conditions, which showed noticeable apoptosis and necroptosis under condition of 2-h ischemia and 24-h reperfusion; next, the preventive or therapeutic effect of emricasan or ponatinib on cerebral I/R injury was tested...
November 4, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29103101/ischemic-preconditioning-protects-astrocytes-against-oxygen-glucose-deprivation-via-the-nuclear-erythroid-2-related-factor-2-pathway
#9
Srinivasan V Narayanan, Kunjan R Dave, Miguel A Perez-Pinzon
Induction of ischemic preconditioning (IPC) represents a potential therapy against cerebral ischemia by activation of adaptive pathways and modulation of mitochondria to induce ischemic tolerance to various cells and tissues. Mitochondrial dysfunction has been ascribed to contribute to numerous neurodegenerative conditions and cerebral ischemia. Nuclear erythroid 2-related factor 2 (Nrf2) is a transcription factor that has traditionally been involved in upregulating cellular antioxidant systems to combat oxidative stress in the brain; however, the association of Nrf2 with mitochondria in the brain remains unclear...
November 4, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29101611/pre-existing-small-vessel-disease-in-patients-with-acute-stroke-from-the-middle-east-southeast-asia-and-philippines
#10
Naveed Akhtar, Abdul Salam, Saadat Kamran, Atlantic D'Souza, Yahia Imam, Ahmed Own, Ahmed ElSotouhy, Surjith Vattoth, Paula Bourke, Zain Bhutta, Sujatha Joseph, Mark Santos, Rabia Ali Khan, Ashfaq Shuaib
Asymptomatic small vessel disease (SVD), including white matter hyperintensities (WMHIs), periventricular hyperintensities (PVHIs), silent stroke (SS), and cerebral microbleeds (CMBs), increases the risk of stroke. There are limited studies of SVD in subjects from the Middle East and Southeast Asia (SA). All patients admitted to stroke service between 2014 and 2015 were reviewed for presence of "pre-existing" SVD. Stroke mimics with no previous history of stroke were used as controls. There were 1727 patients admitted with stroke...
November 3, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29075984/getting-closer-to-an-effective-intervention-of-ischemic-stroke-the-big-promise-of-stem-cell
#11
REVIEW
Deepaneeta Sarmah, Harpreet Kaur, Jackson Saraf, Kanta Pravalika, Avirag Goswami, Kiran Kalia, Anupom Borah, Xin Wang, Kunjan R Dave, Dileep R Yavagal, Pallab Bhattacharya
Stem cell therapy for ischemic stroke has widely been explored. Results from both preclinical and clinical studies have immensely supported the judicious use of stem cells as therapy. These provide an attractive means for preserving and replacing the damaged brain tissues following an ischemic attack. Since the past few years, researchers have used various types of stem cells to replenish insulted neuronal and glial cells in neurological disorders. In the present review, we discuss different types of stem cells employed for the treatment of ischemic stroke and mechanisms and challenges these cells face once introduced into the living system...
October 26, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29067622/factors-mediating-outcome-after-stroke-gender-thrombolysis-and-their-interaction
#12
Seung-Jae Lee, Sung Hyuk Heo, Walter T Ambrosius, Cheryl D Bushnell
Several studies, but not all, have shown that women benefit more from intravenous thrombolysis than men; few have accounted for pre-stroke mobility. Our aim was to determine whether there was an interaction between gender and thrombolysis treatment in 3-month modified Rankin Scale (mRS) score, after adjusting for pre-stroke mobility. We retrospectively reviewed medical records of 1390 consecutive ischemic stroke patients admitted between October 2012 and July 2015. The 3-month mRS was obtained from clinic visits...
October 24, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29039034/inactivation-of-nsf-atpase-leads-to-cathepsin-b-release-after-transient-cerebral-ischemia
#13
Dong Yuan, Chunli Liu, Bingren Hu
Neurons have extraordinary large cell membrane surface area, thus requiring extremely high levels of intracellular membrane-trafficking activities. Consequently, defects in the membrane-trafficking activities preferentially affect neurons. A critical molecule for controlling the membrane-trafficking activities is the N-ethylmaleimide-sensitive factor (NSF) ATPase. This study is to investigate the cascade of events of NSF ATPase inactivation, resulting in a massive buildup of late endosomes (LEs) and fatal release of cathepsin B (CTSB) after transient cerebral ischemia using the 2-vessel occlusion with hypotension (2VO+Hypotension) global brain ischemia model...
October 17, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29034421/hippocampal-deformations-and-entorhinal-cortex-atrophy-as-an-anatomical-signature-of-long-term-cognitive-impairment-from-the-mcao-rat-model-to-the-stroke-patient
#14
C Delattre, C Bournonville, F Auger, R Lopes, C Delmaire, H Henon, A M Mendyk, S Bombois, J C Devedjian, D Leys, C Cordonnier, R Bordet, M Bastide
Stroke patients have an elevated risk of developing long-term cognitive disorders or dementia. The latter is often associated with atrophy of the medial temporal lobe. However, it is not clear whether hippocampal and entorhinal cortex atrophy is the sole predictor of long-term post-stroke dementia. We hypothesized that hippocampal deformation (rather than atrophy) is a predictive marker of long-term post-stroke dementia on a rat model and tested this hypothesis in a prospective cohort of stroke patients.Male Wistar rats were subjected to transient middle cerebral artery occlusion and assessed 6 months later...
October 16, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29027122/hi1a-as-a-novel-neuroprotective-agent-for-ischemic-stroke-by-inhibition-of-acid-sensing-ion-channel-1a
#15
Yandong Ren, Chengchong Li, Jinlong Chang, Rui Wang, Yuhua Wang, Xiang-Ping Chu
Strokes are the second-leading cause of death worldwide, and the cellular and molecular mechanisms underlying stroke-induced brain damage are still uncertain. The present therapy for acute ischemic stroke is limited to thrombolysis with the recombinant tissue plasminogen activator (rtPA). However, rtPA has a narrow therapeutic timeframe of 3-4.5 h, and only approximately 5% of stroke patients can benefit from rtPA treatment. Neuroprotective agents, such as N-methyl-D-aspartate receptor antagonists, have shown great promise in preclinical studies...
October 13, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29022237/dysfunction-of-membrane-trafficking-leads-to-ischemia-reperfusion-injury-after-transient-cerebral-ischemia
#16
REVIEW
Dong Yuan, Chunli Liu, Bingren Hu
Neurons require an extraordinarily high level of membrane trafficking activities because of enriched axonal terminals and dendritic branches. For that reason, defects in the membrane trafficking pathway are a hallmark of most, and may be all, neurodegenerative disorders. A major cellular membrane trafficking pathway is the Golgi apparatus (Golgi hereafter)-late endosome-lysosome axis for supplying lysosomal enzymes. This pathway is regulated by N-ethylmaleimide-sensitive factor (NSF) ATPase. This review article is to discuss a novel hypothesis that brain ischemia inactivates NSF ATPase, resulting in a cascade of events of disruption of the Golgi-endosome-lysosome pathway, release of cathepsin B (CTSB), and induction of mitochondrial outer membrane permeabilization (MOMP) during the postischemic phase...
October 11, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28971348/cerebral-hypoperfusion-and-other-shared-brain-pathologies-in-ischemic-stroke-and-alzheimer-s-disease
#17
Shuying Dong, Shelly Maniar, Mioara D Manole, Dandan Sun
Newly emerged evidence reveals that ischemic stroke and Alzheimer's disease (AD) share pathophysiological changes in brain tissue including hypoperfusion, oxidative stress, immune exhaustion, and inflammation. A mechanistic link between hypoperfusion and amyloid β accumulation can lead to cell damage as well as to motor and cognitive deficits. This review will discuss decreased cerebral perfusion and other related pathophysiological changes common to both ischemic stroke and AD, such as vascular damages, cerebral blood flow alteration, abnormal expression of amyloid β and tau proteins, as well as behavioral and cognitive deficits...
October 2, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28967038/the-protein-modification-and-degradation-pathways-after-brain-ischemia
#18
EDITORIAL
Tibor Kristian, Bingren Hu
No abstract text is available yet for this article.
October 1, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28936802/significance-of-mitochondrial-protein-post-translational-modifications-in-pathophysiology-of-brain-injury
#19
Nina Klimova, Aaron Long, Tibor Kristian
Mitochondria are complex organelles that undergo constant fusion and fission in order to adapt to the ever-changing cellular environment. The fusion/fission proteins, localized in the inner and outer mitochondrial membrane, play critical roles under pathological conditions such as acute brain injury and neurodegenerative diseases. Post-translational modifications of these proteins tightly regulate their function and activity, ultimately impacting mitochondrial dynamics and their efficiency to generate ATP. The individual post-translational modifications that are known to affect mitochondrial dynamics include SUMOylation, ubiquitination, phosphorylation, S-nitrosylation, acetylation, O-linked N-acetyl-glucosamine glycosylation, ADP-ribosylation, and proteolytic cleavage...
September 21, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28900857/endovascular-biopsy-in-vivo-cerebral-aneurysm-endothelial-cell-sampling-and-gene-expression-analysis
#20
Daniel L Cooke, David B McCoy, Van V Halbach, Steven W Hetts, Matthew R Amans, Christopher F Dowd, Randall T Higashida, Devon Lawson, Jeffrey Nelson, Chih-Yang Wang, Helen Kim, Zena Werb, Charles McCulloch, Tomoki Hashimoto, Hua Su, Zhengda Sun
There is limited data describing endothelial cell (EC) gene expression between aneurysms and arteries partly because of risks associated with surgical tissue collection. Endovascular biopsy (EB) is a lower risk alternative to conventional surgical methods, though no such efforts have been attempted for aneurysms. We sought (1) to establish the feasibility of EB to isolate viable ECs by fluorescence-activated cell sorting (FACS), (2) to characterize the differences in gene expression by anatomic location and rupture status using single-cell qPCR, and (3) to demonstrate the utility of unsupervised clustering algorithms to identify cell subpopulations...
September 13, 2017: Translational Stroke Research
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