title: Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of Alexander disease.
abstract: Alexander disease (AxD) is the only known human pathology caused by mutations in an astrocyte-specific gene, glial fibrillary acidic protein (GFAP). These mutations result in abnormal GFAP accumulations that promote seizures, motor delays and, ultimately, death. The exact contribution of increased, abnormal levels of astrocytic mutant GFAP in the development and progression of the epileptic phenotype is not clear, and we addressed this question using two mouse models of AxD. Comparison of brain seizure activity spontaneously and after traumatic brain injury (TBI), an effective way to trigger seizures, revealed that abnormal GFAP accumulation contributes to anomalous brain activity (increased non-convulsive hyperactivity) but is not a risk factor for the development of epilepsy after TBI. These data highlight the need to further explore the complex and heterogeneous response of astrocytes towards injury and the involvement of GFAP in the progression of AxD.
authors: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, 601 Elmwood Ave, Box 645, Rochester, NY 14642, USA. Electronic address: Marisa_Cotrina@URMC.Rochester.edu.
authors: Maria Luisa
authors: ML
authors: Cotrina
authors: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, 601 Elmwood Ave, Box 645, Rochester, NY 14642, USA.
authors: Michael
authors: M
authors: Chen
authors: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, 601 Elmwood Ave, Box 645, Rochester, NY 14642, USA.
authors: Xiaoning
authors: X
authors: Han
authors: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, 601 Elmwood Ave, Box 645, Rochester, NY 14642, USA.
authors: Jeffrey
authors: J
authors: Iliff
authors: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, 601 Elmwood Ave, Box 645, Rochester, NY 14642, USA.
authors: Zeguang
authors: Z
authors: Ren
authors: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, 601 Elmwood Ave, Box 645, Rochester, NY 14642, USA.
authors: Wei
authors: W
authors: Sun
authors: Waisman Center and Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53705, USA.
authors: Tracy
authors: T
authors: Hagemann
authors: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors: James
authors: J
authors: Goldman
authors: Waisman Center and Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53705, USA.
authors: Albee
authors: A
authors: Messing
authors: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, 601 Elmwood Ave, Box 645, Rochester, NY 14642, USA.
authors: Maiken
authors: M
authors: Nedergaard
mesh_terms: D038261:Alexander Disease / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology*; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004827:Epilepsy / Q000503:physiopathology; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology*; D018960:Hyaluronan Receptors / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000473:pathology / Q000503:physiopathology*
chemical_list: C476399:Cd44 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D018960:Hyaluronan Receptors; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse
keywords: Astrocyte; Epilepsy; GFAP; Glia; Trauma