title: Cytokine signaling by grafted neuroectodermal stem cells rescues motoneurons destined to die.
abstract: Following an injury to their axons close to the cell body, adult motoneurons generally die. This type of injury, typically caused by avulsion of the spinal ventral root, initiates the activation of astrocytes and microglial cells and the extracellular space becomes loaded with excessive amounts of excitotoxic glutamate. We have provided evidence that, following ventral root avulsion and reimplantation, murine embryonic neuroectodermal stem cells (NE-GFP-4C) grafted into the rat spinal cord rescue the vast majority of the motoneurons that would otherwise die, and enable them to reinnervate peripheral targets. Stem cell grafts produced the modulatory cytokines IL-1-alpha, IL-6, IL-10, TNF-alpha and MIP-1-alpha, but not neurotrophic factors. The neurons and astrocytes in the ventral horn of grafted animals also produced IL-6 and MIP-1-alpha, indicating a strong interaction between the graft and the host tissue. The infusion of function-blocking antibodies against all cytokines into the grafted cords completely abolished their motoneuron-rescuing effect, while neutralization of only IL-10 suggested its strong effectivity as concerns motoneuron survival and a milder effect on reinnervation. It is suggested that, apart from the anti-inflammatory function of IL-10, the pro-inflammatory cytokines produced exert a strong modulatory function in the CNS, promoting the prevention of neuronal cell death.
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Krisztián
authors.initials: K
authors.lastname: Pajer
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Feichtinger
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Márton
authors.affiliation: VetCORE Technology Centre for Research at the University of Veterinary Medicine, Vienna, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Sabitzer
authors.affiliation: VetCORE Technology Centre for Research at the University of Veterinary Medicine, Vienna, Austria.
authors.forename: Dieter
authors.initials: D
authors.lastname: Klein
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Szeged, Szeged, Hungary; Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria. Electronic address: nogradi.antal@med.u-szeged.hu.
authors.forename: Antal
authors.initials: A
authors.lastname: Nógrádi
mesh_terms: D000578:Amidines; D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D061346:Laser Capture Microdissection; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D053580:Muscle Strength / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D054258:Neural Plate / Q000637:transplantation*; D011843:Radiculopathy / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: D000578:Amidines; D016207:Cytokines; D009419:Nerve Tissue Proteins; C031455:diamidino compound 253-50; D049452:Green Fluorescent Proteins
keywords: Avulsion injury; Motoneuron death; Neuronal survival; Reinnervation