Deborah De Geyter1, Ann De Smedt1,2, Wendy Stoop1, Jacques De Keyser1,2,3, Ron Kooijman1. 1. Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium. 2. Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium. 3. Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands.
Abstract
AIM: Insulin-like growth factor I (IGF-I) is a neuroprotective agent in animal models of ischemic stroke. The purpose of this study was to determine whether systemically injected IGF-I exerts its neuroprotective action by binding to IGF-I receptors in the brain after crossing the blood-brain barrier, or via peripheral effects. METHODS: To differentiate the central effects of IGF-I from systemic effects, ischemic stroke was induced in conscious male Wistar Kyoto rats by the injection of endothelin-1 adjacent to the middle cerebral artery in the right hemisphere, while either the IGF-I receptor antagonist JB-1 or vehicle was introduced into the right lateral ventricle. RESULTS: Intravenous injection of recombinant human (rh)IGF-I resulted in 50% reduction in infarct size, which was counteracted by the central administration of JB-1. Furthermore, rhIGF-I was detected in both the ischemic and nonischemic hemisphere. CONCLUSIONS: Systemically injected rhIGF-I passes the blood-brain barrier and protects neurons via IGF-I receptors in the brain in rats with an ischemic stroke.
AIM: Insulin-like growth factor I (IGF-I) is a neuroprotective agent in animal models of ischemic stroke. The purpose of this study was to determine whether systemically injected IGF-I exerts its neuroprotective action by binding to IGF-I receptors in the brain after crossing the blood-brain barrier, or via peripheral effects. METHODS: To differentiate the central effects of IGF-I from systemic effects, ischemic stroke was induced in conscious male Wistar Kyoto rats by the injection of endothelin-1 adjacent to the middle cerebral artery in the right hemisphere, while either the IGF-I receptor antagonist JB-1 or vehicle was introduced into the right lateral ventricle. RESULTS: Intravenous injection of recombinant human (rh)IGF-I resulted in 50% reduction in infarct size, which was counteracted by the central administration of JB-1. Furthermore, rhIGF-I was detected in both the ischemic and nonischemic hemisphere. CONCLUSIONS: Systemically injected rhIGF-I passes the blood-brain barrier and protects neurons via IGF-I receptors in the brain in rats with an ischemic stroke.
Authors: M Shibata; S Yamada; S R Kumar; M Calero; J Bading; B Frangione; D M Holtzman; C A Miller; D K Strickland; J Ghiso; B V Zlokovic Journal: J Clin Invest Date: 2000-12 Impact factor: 14.808
Authors: An Van Hemelrijck; David Vermijlen; Said Hachimi-Idrissi; Sophie Sarre; Guy Ebinger; Yvette Michotte Journal: J Neurochem Date: 2003-10 Impact factor: 5.372
Authors: Alan Leviton; Elizabeth N Allred; Raina N Fichorova; T Michael O'Shea; Lynn A Fordham; Karl K C Kuban; Olaf Dammann Journal: Eur J Paediatr Neurol Date: 2018-01-31 Impact factor: 3.140
Authors: Marion Walser; Johan Svensson; Lars Karlsson; Reza Motalleb; Maria Åberg; H Georg Kuhn; Jörgen Isgaard; N David Åberg Journal: Front Endocrinol (Lausanne) Date: 2021-01-08 Impact factor: 5.555
Authors: Santiago Guerra-Cantera; Laura M Frago; Francisca Díaz; Purificacion Ros; Maria Jiménez-Hernaiz; Alejandra Freire-Regatillo; Vicente Barrios; Jesús Argente; Julie A Chowen Journal: Front Endocrinol (Lausanne) Date: 2020-08-11 Impact factor: 5.555