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      Neuronal activity drives localized blood-brain-barrier transport of serum insulin-like growth factor-I into the CNS.

      Neuron

      innervation, Vibrissae, Time Factors, physiology, drug effects, Regional Blood Flow, metabolism, Receptor, IGF Type 1, Rats, Wistar, Rats, Protein Transport, ultrastructure, Neurons, Neuroglia, Neural Pathways, Nerve Tissue Proteins, methods, Microscopy, Immunoelectron, Microdialysis, Matrix Metalloproteinase 9, Low Density Lipoprotein Receptor-Related Protein-1, pharmacology, Insulin-Like Growth Factor I, Immunoprecipitation, Humans, Glutamic Acid, Functional Laterality, Excitatory Amino Acid Antagonists, Enzyme-Linked Immunosorbent Assay, Endothelial Cells, Electric Stimulation, Drug Interactions, Digoxigenin, Coculture Techniques, Central Nervous System, Cells, Cultured, Body Temperature, Blood-Brain Barrier, Biophysics, Animals, Analysis of Variance, Action Potentials

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          Abstract

          Upon entry into the central nervous system (CNS), serum insulin-like growth factor-1 (IGF-I) modulates neuronal growth, survival, and excitability. Yet mechanisms that trigger IGF-I entry across the blood-brain barrier remain unclear. We show that neuronal activity elicited by electrical, sensory, or behavioral stimulation increases IGF-I input in activated regions. Entrance of serum IGF-I is triggered by diffusible messengers (i.e., ATP, arachidonic acid derivatives) released during neurovascular coupling. These messengers stimulate matrix metalloproteinase-9, leading to cleavage of the IGF binding protein-3 (IGFBP-3). Cleavage of IGFBP-3 allows the passage of serum IGF-I into the CNS through an interaction with the endothelial transporter lipoprotein related receptor 1. Activity-dependent entrance of serum IGF-I into the CNS may help to explain disparate observations such as proneurogenic effects of epilepsy, rehabilitatory effects of neural stimulation, and modulatory effects of blood flow on brain activity. 2010 Elsevier Inc. All rights reserved.

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          Journal
          10.1016/j.neuron.2010.08.007
          20826314

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