title: Leukemia Inhibitory Factor Haplodeficiency Desynchronizes Glial Reactivity and Exacerbates Damage and Functional Deficits after a Concussive Brain Injury.
abstract: Reactions of both astrocytes and microglia to central nervous system injury can be beneficial or detrimental to recovery. To gain insights into the functional importance of gliosis, we developed a new model of adolescent closed-head injury (CHI) and interrogated the behavioral, physiological, and cellular outcomes after a concussive CHI in leukemia inhibitory factor (LIF) haplodeficient mice. These mice were chosen because LIF is important for astrocyte and microglial activation. Behaviorally, the LIF haplodeficient animals were equally impaired 4 h after the injury, but in the subsequent 2 weeks, the LIF haplodeficient mice acquired more severe motor and sensory deficits, compared with wild type mice. The prolonged accumulation of neurological impairment was accompanied by desynchronization of the gliotic response, increased cell death, axonal degeneration, diminished callosal compound action potential, and hypomyelination. Our results clearly show that LIF is an essential injury-induced cytokine that is required to prevent the propagation of secondary neurodegeneration.
authors.affiliation: 1 Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School , Newark, New Jersey.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Goodus
authors.affiliation: 1 Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School , Newark, New Jersey.
authors.forename: Nadine A
authors.initials: NA
authors.lastname: Kerr
authors.affiliation: 1 Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School , Newark, New Jersey.
authors.forename: Ruchika
authors.initials: R
authors.lastname: Talwar
authors.affiliation: 1 Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School , Newark, New Jersey.
authors.forename: David
authors.initials: D
authors.lastname: Buziashvili
authors.affiliation: 1 Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School , Newark, New Jersey.|2 Veterans Affairs Medical Center , New Jersey Health Care System, East Orange, New Jersey.
authors.forename: Jennifer E C
authors.initials: JE
authors.lastname: Fragale
authors.affiliation: 1 Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School , Newark, New Jersey.|2 Veterans Affairs Medical Center , New Jersey Health Care System, East Orange, New Jersey.
authors.forename: Kevin C H
authors.initials: KC
authors.lastname: Pang
authors.affiliation: 1 Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School , Newark, New Jersey.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Levison
mesh_terms: D000818:Animals; D016207:Cytokines / Q000172:deficiency / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D016489:Head Injuries, Closed / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology*; D053605:Leukemia Inhibitory Factor / Q000172:deficiency / Q000502:physiology*; D008297:Male; D051379:Mice
chemical_list: D016207:Cytokines; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse
keywords: astrogliosis; cytokines; microglia; motor function; trauma