title: Cellular reactions and compensatory tissue re-organization during spontaneous recovery after spinal cord injury in neonatal mice.
abstract: Following incomplete spinal cord injuries, neonatal mammals display a remarkable degree of behavioral recovery. Previously, we have demonstrated in neonatal mice a wholesale re-establishment and reorganization of synaptic connections from some descending axon tracts (Boulland et al.: PLoS One 8 (2013)). To assess the potential cellular mechanisms contributing to this recovery, we have here characterized a variety of cellular sequelae following thoracic compression injuries, focusing particularly on cell loss and proliferation, inflammation and reactive gliosis, and the dynamics of specific types of synaptic terminals. Early during the period of recovery, regressive events dominated. Tissue loss near the injury was severe, with about 80% loss of neurons and a similar loss of axons that later make up the white matter. There was no sign of neurogenesis, no substantial astroglial or microglial proliferation, no change in the ratio of M1 and M2 microglia and no appreciable generation of the terminal complement peptide C5a. One day after injury the number of synaptic terminals on lumbar motoneurons had dropped by a factor of 2, but normalized by 6 days. The ratio of VGLUT1/2+ to VGAT+ terminals remained similar in injured and uninjured spinal cords during this period. By 24 days after injury, when functional recovery is nearly complete, the density of 5-HT+ fibers below the injury site had increased by a factor of 2.5. Altogether this study shows that cellular reactions are diverse and dynamic. Pronounced recovery of both excitatory and inhibitory terminals and an increase in serotonergic innervation below the injury, coupled with a general lack of inflammation and reactive gliosis, are likely to contribute to the recovery. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 928-946, 2017.
authors.affiliation: Laboratory of Neural Development and Optical Recording (NDEVOR), Division of Physiology, Department of Molecular Medicine, University of Oslo.
authors.forename: Rishab S
authors.initials: RS
authors.lastname: Chawla
authors.affiliation: Norwegian Center for Stem Cell Research, Oslo University Hospital.|Department of Neurosurgery, Oslo University Hospital.
authors.forename: Mark
authors.initials: M
authors.lastname: Züchner
authors.affiliation: Laboratory of Neural Development and Optical Recording (NDEVOR), Division of Physiology, Department of Molecular Medicine, University of Oslo.
authors.forename: Maria
authors.initials: M
authors.lastname: Mastrangelopoulou
authors.affiliation: Laboratory of Neural Development and Optical Recording (NDEVOR), Division of Physiology, Department of Molecular Medicine, University of Oslo.|INCIA CNRS UMR 5287 Université de Bordeaux, Bordeaux, France.
authors.forename: François M
authors.initials: FM
authors.lastname: Lambert
authors.affiliation: Laboratory of Neural Development and Optical Recording (NDEVOR), Division of Physiology, Department of Molecular Medicine, University of Oslo.|Norwegian Center for Stem Cell Research, Oslo University Hospital.
authors.forename: Joel C
authors.initials: JC
authors.lastname: Glover
authors.affiliation: Laboratory of Neural Development and Optical Recording (NDEVOR), Division of Physiology, Department of Molecular Medicine, University of Oslo.|Norwegian Center for Stem Cell Research, Oslo University Hospital.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Boulland
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology; D008070:Lipopolysaccharides; D008297:Male; D008813:Mice, Inbred ICR; D017628:Microglia / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D058630:Spinal Cord Regeneration / Q000502:physiology*; D013569:Synapses / Q000473:pathology / Q000502:physiology; D066127:White Matter / Q000473:pathology / Q000503:physiopathology
chemical_list: D008070:Lipopolysaccharides; D012701:Serotonin
keywords: adaptive plasticity; network re-organization; recovery; spinal cord injury; sprouting