Intranasal administration of aTf protects and repairs the neonatal white matter after a cerebral hypoxic-ischemic event.

Abstract	Our previous studies showed that the intracerebral injection of apotransferrin (aTf) attenuates white matter damage and accelerates the remyelination process in a neonatal rat model of cerebral hypoxia-ischemia (HI) injury. However, the intracerebral injection of aTf might not be practical for clinical treatments. Therefore, the development of less invasive techniques capable of delivering aTf to the central nervous system would clearly aid in its effective clinical use. In this work, we have determined whether intranasal (iN) administration of human aTf provides neuroprotection to the neonatal mouse brain following a cerebral hypoxic-ischemic event. Apotransferrin was infused into the naris of neonatal mice and the HI insult was induced by right common carotid artery ligation followed by exposure to low oxygen concentration. Our results showed that aTf was successfully delivered into the neonatal HI brain and detected in the olfactory bulb, forebrain and posterior brain 30 min after inhalation. This treatment successfully reduced white matter damage, neuronal loss and astrogliosis in different brain regions and enhanced the proliferation and survival of oligodendroglial progenitor cells (OPCs) in the subventricular zone and corpus callosum (CC). Additionally, using an in vitro hypoxic model, we demonstrated that aTf prevents oligodendrocyte progenitor cell death by promoting their differentiation. In summary, these data suggest that iN administration of aTf has the potential to be used for clinical treatment to protect myelin and to induce remyelination in demyelinating hypoxic-ischemic events in the neonatal brain.
Authors	Mariano Guardia Clausi, Pablo M Paez, Anthony T Campagnoni, Laura A Pasquini, Juana M Pasquini
Journal	Glia (Glia) Vol. 60 Issue 10 Pg. 1540-54 (Oct 2012) ISSN: 1098-1136 [Electronic] United States
PMID	22736466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2012 Wiley Periodicals, Inc.
Chemical References	Antigens Apoproteins Autophagy-Related Proteins Intermediate Filament Proteins Intracellular Signaling Peptides and Proteins Myelin Basic Protein NES protein, human Nerve Tissue Proteins Nes protein, mouse Nes protein, rat Nestin Neuroprotective Agents Platelet-Derived Growth Factor Proteoglycans Rb1cc1 protein, mouse SOXB1 Transcription Factors Sox2 protein, mouse Transferrin apotransferrin chondroitin sulfate proteoglycan 4 enhanced green fluorescent protein platelet-derived growth factor A Green Fluorescent Proteins Cytochalasin B 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase Cnp protein, mouse Caspase 3 Bromodeoxyuridine Colchicine
Topics	2',3'-Cyclic Nucleotide 3'-Phosphodiesterase (genetics) Administration, Intranasal Age Factors Animals Animals, Newborn Antigens (metabolism) Apoproteins (administration & dosage) Autophagy-Related Proteins Brain Injuries (etiology, prevention & control) Bromodeoxyuridine (metabolism) Caspase 3 (metabolism) Cell Death (drug effects, genetics) Cell Proliferation (drug effects) Cells, Cultured Cerebral Cortex (cytology) Colchicine (pharmacology) Corpus Callosum (drug effects, pathology) Cytochalasin B (pharmacology) Female Gene Expression Regulation (drug effects, genetics) Green Fluorescent Proteins (genetics) Humans Hypoxia (drug therapy) Hypoxia-Ischemia, Brain (complications, drug therapy, pathology) Intermediate Filament Proteins (metabolism) Intracellular Signaling Peptides and Proteins (metabolism) Lateral Ventricles (drug effects, physiology) Male Mice Mice, Transgenic Myelin Basic Protein (metabolism) Nerve Fibers, Myelinated (drug effects, metabolism) Nerve Tissue Proteins (metabolism) Nestin Neurogenesis (drug effects) Neuroprotective Agents (administration & dosage) Oligodendroglia (drug effects) Platelet-Derived Growth Factor (metabolism) Proteoglycans (metabolism) SOXB1 Transcription Factors (metabolism) Time Factors Transferrin (administration & dosage)

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