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      Zebrafish models of cerebrovascular disease

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          Abstract

          Perturbations in cerebral blood flow and abnormalities in blood vessel structure are the hallmarks of cerebrovascular disease. While there are many genetic and environmental factors that affect these entities through a heterogeneous group of disease processes, the ultimate final pathologic insult in humans is defined as a stroke, or damage to brain parenchyma. In the case of ischemic stroke, blood fails to reach its target destination whereas in hemorrhagic stroke, extravasation of blood occurs outside of the blood vessel lumen, resulting in direct damage to brain parenchyma. As these acute events can be neurologically devastating, if not fatal, development of novel therapeutics are urgently needed. The zebrafish ( Danio rerio) is an attractive model for the study of cerebrovascular disease because of its morphological and physiological similarity to human cerebral vasculature, its ability to be genetically manipulated, and its fecundity allowing for large-scale, phenotype-based screens.

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          Efficient In Vivo Genome Editing Using RNA-Guided Nucleases

          Woong Hwang, Yanfang Fu, Deepak Reyon … (2013)
          Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems have evolved in bacteria and archaea as a defense mechanism to silence foreign nucleic acids of viruses and plasmids. Recent work has shown that bacterial type II CRISPR systems can be adapted to create guide RNAs (gRNAs) capable of directing site-specific DNA cleavage by the Cas9 nuclease in vitro. Here we show that this system can function in vivo to induce targeted genetic modifications in zebrafish embryos with efficiencies comparable to those obtained using ZFNs and TALENs for the same genes. RNA-guided nucleases robustly enabled genome editing at 9 of 11 different sites tested, including two for which TALENs previously failed to induce alterations. These results demonstrate that programmable CRISPR/Cas systems provide a simple, rapid, and highly scalable method for altering genes in vivo, opening the door to using RNA-guided nucleases for genome editing in a wide range of organisms.
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            Molecular regulation of vessel maturation.

            Rakesh Jain (2003)
            The maturation of nascent vasculature, formed by vasculogenesis or angiogenesis, requires recruitment of mural cells, generation of an extracellular matrix and specialization of the vessel wall for structural support and regulation of vessel function. In addition, the vascular network must be organized so that all the parenchymal cells receive adequate nutrients. All of these processes are orchestrated by physical forces as well as by a constellation of ligands and receptors whose spatio-temporal patterns of expression and concentration are tightly regulated. Inappropriate levels of these physical forces or molecules produce an abnormal vasculature--a hallmark of various pathologies. Normalization of the abnormal vasculature can facilitate drug delivery to tumors and formation of a mature vasculature can help realize the promise of therapeutic angiogenesis and tissue engineering.
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              International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion.

              Andrew J. Molyneux, Richard Kerr, Ly-Mee Yu … (2005)
              Two types of treatment are being used for patients with ruptured intracranial aneurysms: endovascular detachable-coil treatment or craniotomy and clipping. We undertook a randomised, multicentre trial to compare these treatments in patients who were suitable for either treatment because the relative safety and efficacy of these approaches had not been established. Here we present clinical outcomes 1 year after treatment. 2143 patients with ruptured intracranial aneurysms, who were admitted to 42 neurosurgical centres, mainly in the UK and Europe, took part in the trial. They were randomly assigned to neurosurgical clipping (n=1070) or endovascular coiling (n=1073). The primary outcome was death or dependence at 1 year (defined by a modified Rankin scale of 3-6). Secondary outcomes included rebleeding from the treated aneurysm and risk of seizures. Long-term follow up continues. Analysis was in accordance with the randomised treatment. We report the 1-year outcomes for 1063 of 1073 patients allocated to endovascular treatment, and 1055 of 1070 patients allocated to neurosurgical treatment. 250 (23.5%) of 1063 patients allocated to endovascular treatment were dead or dependent at 1 year, compared with 326 (30.9%) of 1055 patients allocated to neurosurgery, an absolute risk reduction of 7.4% (95% CI 3.6-11.2, p=0.0001). The early survival advantage was maintained for up to 7 years and was significant (log rank p=0.03). The risk of epilepsy was substantially lower in patients allocated to endovascular treatment, but the risk of late rebleeding was higher. In patients with ruptured intracranial aneurysms suitable for both treatments, endovascular coiling is more likely to result in independent survival at 1 year than neurosurgical clipping; the survival benefit continues for at least 7 years. The risk of late rebleeding is low, but is more common after endovascular coiling than after neurosurgical clipping.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Cereb Blood Flow Metab
                Journal ID (iso-abbrev): J. Cereb. Blood Flow Metab
                Title: Journal of Cerebral Blood Flow & Metabolism
                Publisher: Nature Publishing Group
                ISSN (Print): 0271-678X
                ISSN (Electronic): 1559-7016
                Publication date (Print): April 2014
                Publication date (Electronic): 12 February 2014
                Publication date PMC-release: 1 April 2014
                Volume: 34
                Issue: 4
                Pages: 571-577
                Affiliations
                [1 ]Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts, USA
                [2 ]Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School , Charlestown, Massachusetts, USA
                [3 ]Broad Institute , Cambridge, Massachusetts, USA
                Author notes
                [* ]Department of Neurological Surgery, Massachusetts General Hospital and Harvard Medical School , 55 Fruit Street, White Building Room 502, Boston, MA 02114, USA. E-mail: walcott.brian@ 123456mgh.harvard.edu
                Article
                Publisher Item ID: jcbfm201427
                DOI: 10.1038/jcbfm.2014.27
                PMC ID: 3982096
                PubMed ID: 24517974
                SO-VID: bfa96094-45e6-470d-9c08-c5066ff69bf7
                Copyright © Copyright © 2014 International Society for Cerebral Blood Flow & Metabolism, Inc.
                License:

                This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/

                History
                Date received : 11 November 2013
                Date revision received : 27 December 2013
                Date accepted : 07 January 2014
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Neurosciences
                Keywords: aneurysm,arteriovenous malformation,cavernous malformation,moyamoya,stroke,zebrafish
                Data availability:
                ScienceOpen disciplines: Neurosciences
                Keywords: aneurysm, arteriovenous malformation, cavernous malformation, moyamoya, stroke, zebrafish

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