Neuroserpin, a neuroprotective factor in focal ischemic stroke

Molecular and Cellular Neurosciences
Paolo CinelliPeter Sonderegger

Abstract

Because recent studies have indicated that tissue plasminogen activator (tPA) aggravates neurodegenerative processes in many neural pathologies, we studied whether the endogenous tPA antagonist neuroserpin has a neuroprotective effect in an animal model of focal ischemic stroke. After induction of a focal ischemic stroke in the mouse by occlusion of the middle cerebral artery, we found that microglial cells accumulated in the marginal zone of the infarct are the most important source for both plasminogen activators, tPA and uPA. To investigate the effect of neuroserpin on the size and the histology of the infarct we produced transgenic mice overexpressing neuroserpin approximately sixfold in the nervous system. In the brain of these mice the total tPA activity in the uninjured tissue was strongly reduced. After induction of a focal ischemic stroke in the transgenic mice by a permanent occlusion of the middle cerebral artery (MCA), the infarcts were 30% smaller than in the wild-type mice. Immunohistochemical analyses and in situ hybridization revealed an attenuation of the microglial activation in the reactive zone. Concomitantly, the microglial production of tPA and uPA, as well as the PA-activity in the infarct region was mark...Continue Reading

References

Jul 1, 1991·Journal of Reproduction and Fertility·I WilmutJ P Simons
Jul 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·J L UrbanH Schreiber
Jan 1, 1987·Journal of Neuroscience Research·D Giulian
Jul 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·R L BrinsterR D Palmiter
Oct 29, 1993·Science·J T Coyle, P Puttfarcken
Mar 3, 1994·The New England Journal of Medicine·S A Lipton, P A Rosenberg
Jul 1, 1994·Brain Research. Molecular Brain Research·K A KelleyK Herrup
Aug 1, 1993·The Journal of Clinical Investigation·A P SappinoJ D Vassalli
Jan 1, 1993·Stroke; a Journal of Cerebral Circulation·T N LinC Y Hsu
Aug 1, 1996·Trends in Neurosciences·G W Kreutzberg
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·S E TsirkaS Strickland

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Citations

Jun 20, 2013·Therapeutic Hypothermia and Temperature Management·Xian Nan TangMidori A Yenari
Jun 19, 2002·The Journal of Clinical Investigation·Manuel YepesDaniel A Lawrence
Nov 18, 2003·The Journal of Clinical Investigation·Manuel YepesDaniel A Lawrence
May 17, 2011·Journal of Translational Medicine·Raquel Rodríguez-GonzálezJosé Castillo
Jul 10, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dianer YangChia-Yi Kuan
Jul 21, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Fang WuManuel Yepes
May 16, 2009·Molecular and Cellular Neurosciences·Ping-Yen ChenCheng-Wen Wu
Oct 18, 2007·Molecular and Cellular Neurosciences·Peter ThorntonNancy J Rothwell
Sep 18, 2007·Progress in Neurobiology·Chen Xu Wang, Ashfaq Shuaib
May 20, 2003·The European Journal of Neuroscience·Patrizia Wannier-MorinoDetlev Grabs
Dec 3, 2009·Protein Science : a Publication of the Protein Society·Didier BelorgeyDavid A Lomas
Jul 21, 2004·Trends in Cardiovascular Medicine·Manuel Yepes, Daniel A Lawrence
Sep 9, 2015·Frontiers in Cellular Neuroscience·Manuel Yepes
Jan 23, 2008·Expert Opinion on Therapeutic Targets·Iordanis Gravanis, Stella E Tsirka
Jul 23, 2004·Expert Opinion on Therapeutic Targets·Nathalie LebeurrierCarine Ali
Dec 18, 2010·Neurochemistry International·Raquel Rodríguez-GonzálezJosé Castillo
Aug 12, 2016·Journal of Molecular Neuroscience : MN·Yong ChengNigel P Birch
Sep 19, 2016·Seminars in Cell & Developmental Biology·Tet Woo LeeNigel P Birch
Jun 11, 2003·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Heike BeckKarl H Plate
May 15, 2018·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Jiping YangHuaijun Liu
Jul 13, 2004·The Journal of Biological Chemistry·Olivier PoirotStephan Kellenberger

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