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Nogo-A targeted therapy promotes vascular repair and functional recovery following stroke.

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Title: Nogo-A targeted therapy promotes vascular repair and functional recovery following stroke.
Authors: Rust, Ruslan1,2 rust@irem.uzh.ch, Grönnert, Lisa1, Gantner, Christina3, Enzler, Alinda2, Mulders, Geertje1, Weber, Rebecca Z.1, Siewert, Arthur4, Limasale, Yanuar D. P.5, Meinhardt, Andrea5, Maurer, Michael A.1, Sartori, Andrea M.1,2, Hofer, Anna-Sophie1,2, Werner, Carsten5, Schwab, Martin E.1,2 schwab@irem.uzh.ch
Source: Proceedings of the National Academy of Sciences of the United States of America. 7/9/2019, Vol. 116 Issue 28, p14270-14279. 10p.
Subjects: Nogo protein, Cerebral ischemia, Spinal cord injuries, Central nervous system, Stroke
Abstract: Stroke is a major cause of serious disability due to the brain's limited capacity to regenerate damaged tissue and neuronal circuits. After ischemic injury, a multiphasic degenerative and inflammatory response is coupled with severely restricted vascular and neuronal repair, resulting in permanent functional deficits. Although clinical evidence indicates that revascularization of the ischemic brain regions is crucial for functional recovery, no therapeutics that promote angiogenesis after cerebral stroke are currently available. Besides vascular growth factors, guidance molecules have been identified to regulate aspects of angiogenesis in the central nervous system (CNS) and may provide targets for therapeutic angiogenesis. In this study, we demonstrate that genetic deletion of the neurite outgrowth inhibitor Nogo-A or one of its corresponding receptors, S1PR2, improves vascular sprouting and repair and reduces neurological deficits after cerebral ischemia in mice. These findings were reproduced in a therapeutic approach using intrathecal anti-Nogo-A antibodies; such a therapy is currently in clinical testing for spinal cord injury. These results provide a basis for a therapeutic blockage of inhibitory guidance molecules to improve vascular and neural repair after ischemic CNS injuries. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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PubType: Academic Journal
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  Data: Nogo-A targeted therapy promotes vascular repair and functional recovery following stroke.
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  Data: <searchLink fieldCode="AR" term="%22Rust%2C+Ruslan%22">Rust, Ruslan</searchLink><relatesTo>1,2</relatesTo><i> rust@irem.uzh.ch</i><br /><searchLink fieldCode="AR" term="%22Grönnert%2C+Lisa%22">Grönnert, Lisa</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Gantner%2C+Christina%22">Gantner, Christina</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Enzler%2C+Alinda%22">Enzler, Alinda</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Mulders%2C+Geertje%22">Mulders, Geertje</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Weber%2C+Rebecca+Z%2E%22">Weber, Rebecca Z.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Siewert%2C+Arthur%22">Siewert, Arthur</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Limasale%2C+Yanuar+D%2E+P%2E%22">Limasale, Yanuar D. P.</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Meinhardt%2C+Andrea%22">Meinhardt, Andrea</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Maurer%2C+Michael+A%2E%22">Maurer, Michael A.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Sartori%2C+Andrea+M%2E%22">Sartori, Andrea M.</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Hofer%2C+Anna-Sophie%22">Hofer, Anna-Sophie</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Werner%2C+Carsten%22">Werner, Carsten</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Schwab%2C+Martin+E%2E%22">Schwab, Martin E.</searchLink><relatesTo>1,2</relatesTo><i> schwab@irem.uzh.ch</i>
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  Data: Stroke is a major cause of serious disability due to the brain's limited capacity to regenerate damaged tissue and neuronal circuits. After ischemic injury, a multiphasic degenerative and inflammatory response is coupled with severely restricted vascular and neuronal repair, resulting in permanent functional deficits. Although clinical evidence indicates that revascularization of the ischemic brain regions is crucial for functional recovery, no therapeutics that promote angiogenesis after cerebral stroke are currently available. Besides vascular growth factors, guidance molecules have been identified to regulate aspects of angiogenesis in the central nervous system (CNS) and may provide targets for therapeutic angiogenesis. In this study, we demonstrate that genetic deletion of the neurite outgrowth inhibitor Nogo-A or one of its corresponding receptors, S1PR2, improves vascular sprouting and repair and reduces neurological deficits after cerebral ischemia in mice. These findings were reproduced in a therapeutic approach using intrathecal anti-Nogo-A antibodies; such a therapy is currently in clinical testing for spinal cord injury. These results provide a basis for a therapeutic blockage of inhibitory guidance molecules to improve vascular and neural repair after ischemic CNS injuries. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=137465792
RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1073/pnas.1905309116
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      – Code: eng
        Text: English
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        PageCount: 10
        StartPage: 14270
    Subjects:
      – SubjectFull: Nogo protein
        Type: general
      – SubjectFull: Cerebral ischemia
        Type: general
      – SubjectFull: Spinal cord injuries
        Type: general
      – SubjectFull: Central nervous system
        Type: general
      – SubjectFull: Stroke
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      – TitleFull: Nogo-A targeted therapy promotes vascular repair and functional recovery following stroke.
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              Text: 7/9/2019
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              Y: 2019
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