Contraindications of VEGF-based therapeutic angiogenesis: effects on macrophage density and histology of normal and ischemic brains

Vascular Pharmacology
Panya S ManoonkitiwongsaPatrick D Lyden

Abstract

Therapeutic angiogenesis by vascular endothelial growth factor (VEGF) is advocated as a promising treatment strategy for brain ischemic stroke. However, data in the literature demonstrating the benefit of therapeutic angiogenesis are contradictory. In this paper, we describe the effects of non-angiogenic and angiogenic doses of VEGF165 on macrophage density and histology of normal and ischemic brains of adult rats. VEGF165 was administered intra-arterially for 7 days following temporary occlusion of the middle cerebral artery. In contrast to ischemic brains treated with non-angiogenic doses of VEGF165 which showed preserved neuropil and reduced numbers of macrophages, ischemic brains treated by an angiogenic dose showed phagocytized neuropil and high macrophage density. Though neither non-angiogenic nor angiogenic doses caused macrophage infiltration in normal brains, damage of the brain matrix occurred with the angiogenic dose. These results suggest an angiogenic dose of VEGF165 injures the nervous tissue rather than promote recovery. Angiogenesis by VEGF monotherapy for ischemic stroke should be viewed with caution, or avoided. Since our data show intravascular administration of VEGF165 does not cause macrophage inflammation,...Continue Reading

References

Jan 1, 1989·Stroke; a Journal of Cerebral Circulation·E Z LongaR Cummins
May 1, 1989·Stroke; a Journal of Cerebral Circulation·L PerssonY Olsson
May 1, 1986·Stroke; a Journal of Cerebral Circulation·J B BedersonH Bartkowski
Apr 1, 1996·Journal of Korean Medical Science·J W ShimJ G Chi
Dec 22, 1998·The American Journal of Cardiology·J M Isner
Apr 28, 1999·Journal of Neuropathology and Experimental Neurology·K H Plate
Jun 22, 1999·Journal of Neuropathology and Experimental Neurology·M A ProescholdtM J Merrill
Dec 10, 1999·The Journal of Clinical Investigation·N van BruggenN Ferrara
Oct 13, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·P S ManoonkitiwongsaP D Lyden
Jan 30, 2002·Acta Haematologica·N Ferrara, H P Gerber
Feb 20, 2002·Trends in Cardiovascular Medicine·Zhenggang Zhang, Michael Chopp
Mar 29, 2002·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Zheng Gang ZhangMichael Chopp
Apr 24, 2002·Seminars in Cell & Developmental Biology·Peter Carmeliet, Erik Storkebaum
Aug 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Kunlin JinDavid A Greenberg
Oct 23, 2002·Brain : a Journal of Neurology·Heike J SchochHugo H Marti
Oct 31, 2002·Cerebrovascular Diseases·Julien BogousslavskyUNKNOWN European-Australian Fiblast (Trafermin) in Acute Stroke Group
Nov 6, 2002·Journal of Neuroimmunology·Frauke ForstreuterRolf Mentlein
Feb 20, 2003·Journal of Hematotherapy & Stem Cell Research·Zhao Zhong ChongKenneth Maiese
May 16, 2003·Vascular Pharmacology·D O Bates, S J Harper
Jul 16, 2003·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Maria BellomoGioacchino Calapai
Sep 27, 2003·European Journal of Clinical Investigation·D RibattiM Presta
Jan 15, 2004·Trends in Molecular Medicine·David A Greenberg, Kunlin Jin
May 18, 2004·Experimental Neurology·Susan D CrollStanley J Wiegand
Jun 8, 2004·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Panya S ManoonkitiwongsaPatrick D Lyden
Jul 20, 2004·Nature Genetics·Lei CaoMatthew J During
Aug 10, 2004·The Journal of Experimental Biology·Hugo H Marti
Sep 8, 2004·Journal of Cellular Biochemistry·L MalaguarneraS Sanfilippo
Dec 21, 2004·Journal of Korean Medical Science·Joo Han KimHoon Kap Lee
Dec 24, 2004·Drug News & Perspectives·D A Greenberg
Jan 29, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Jieli ChenMichael Chopp
Feb 18, 2005·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Yu Dennis ChengJustin A Zivin
Feb 18, 2005·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Dafang Wu
Apr 15, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Dilaver KayaTurgay Dalkara
May 20, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Samuel ValableEdwige Petit

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Citations

Mar 29, 2014·American Journal of Respiratory Cell and Molecular Biology·Yun Sil ChangWon Soon Park
Jul 3, 2007·Current Treatment Options in Cardiovascular Medicine·Juan F ArenillasAntoni Dávalos
Mar 16, 2007·Expert Opinion on Emerging Drugs·Paul A Lapchak, Dalia M Araujo
Aug 6, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Dirk Matthias Hermann, Anil Zechariah
Sep 17, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Tomás SobrinoJosé Castillo
Oct 30, 2007·Neurologic Clinics·Geoffrey S Young
Jun 21, 2012·Journal of Neuroscience Research·Yihui MaDirk M Hermann
Dec 18, 2009·Journal of Cellular and Molecular Medicine·S LanfranconiA Bersano
Apr 14, 2009·Cell Adhesion & Migration·Deepti NavaratnaEng H Lo
May 7, 2016·Expert Review of Neurotherapeutics·Hung NguyenCesario V Borlongan
Apr 4, 2009·Physiological Reviews·Carmen Ruiz de AlmodovarPeter Carmeliet
Jan 11, 2020·Acta Neurologica Scandinavica·N David ÅbergJohan Svensson
Mar 31, 2015·Stroke; a Journal of Cerebral Circulation·Joanna Adamczak, Mathias Hoehn
Aug 11, 2020·Stroke; a Journal of Cerebral Circulation·Su Jing ChanVictor Nurcombe
Dec 22, 2016·Journal of Clinical Laboratory Analysis·Jun ZhengZhenzeng Fan

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