Central IGF-I Receptors in the Brain Are Instrumental to Neuroprotection by Systemically Injected IGF-I in a Rat Model for Ischemic Stroke
Overview
Pharmacology
Affiliations
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.
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