Open AccessCentral IGF ‐I Receptors in the Brain are Instrumental to Neuroprotection by Systemically Injected IGF ‐I in a Rat Model for Ischemic Stroke
Author(s) -
De Geyter Deborah,
De Smedt Ann,
Stoop Wendy,
De Keyser Jacques,
Kooijman Ron
Publication year - 2016
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12550
Subject(s) - neuroprotection , receptor , medicine , stroke (engine) , antagonist , pharmacology , blood–brain barrier , receptor antagonist , endocrinology , central nervous system , mechanical engineering , engineering
Summary 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, rh IGF ‐I was detected in both the ischemic and nonischemic hemisphere. Conclusions Systemically injected rh IGF ‐I passes the blood–brain barrier and protects neurons via IGF ‐I receptors in the brain in rats with an ischemic stroke.