Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of Alexander disease

Maria Luisa Cotrina, Michael Chen, Xiaoning Han, Jeffrey Iliff, Zeguang Ren, Wei Sun, Tracy Hagemann, James Goldman, Albee Messing, Maiken Nedergaard

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)211-219
Number of pages9
JournalBrain Research
Volume1582
DOIs
StatePublished - Sep 25 2014
Externally publishedYes

Fingerprint

Alexander Disease
Glial Fibrillary Acidic Protein
Seizures
Astrocytes
Mutation
Brain
Mutant Proteins
Epilepsy
Traumatic Brain Injury
Pathology
Phenotype
Wounds and Injuries
Genes

Keywords

  • Astrocyte
  • Epilepsy
  • GFAP
  • Glia
  • Trauma

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of Alexander disease. / Cotrina, Maria Luisa; Chen, Michael; Han, Xiaoning; Iliff, Jeffrey; Ren, Zeguang; Sun, Wei; Hagemann, Tracy; Goldman, James; Messing, Albee; Nedergaard, Maiken.

In: Brain Research, Vol. 1582, 25.09.2014, p. 211-219.

Research output: Contribution to journalArticle

Cotrina, ML, Chen, M, Han, X, Iliff, J, Ren, Z, Sun, W, Hagemann, T, Goldman, J, Messing, A & Nedergaard, M 2014, 'Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of Alexander disease', Brain Research, vol. 1582, pp. 211-219. https://doi.org/10.1016/j.brainres.2014.07.029
Cotrina, Maria Luisa ; Chen, Michael ; Han, Xiaoning ; Iliff, Jeffrey ; Ren, Zeguang ; Sun, Wei ; Hagemann, Tracy ; Goldman, James ; Messing, Albee ; Nedergaard, Maiken. / Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of Alexander disease. In: Brain Research. 2014 ; Vol. 1582. pp. 211-219.
@article{480fbe444ee443149073443ce70d374a,
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.",
keywords = "Astrocyte, Epilepsy, GFAP, Glia, Trauma",
author = "Cotrina, {Maria Luisa} and Michael Chen and Xiaoning Han and Jeffrey Iliff and Zeguang Ren and Wei Sun and Tracy Hagemann and James Goldman and Albee Messing and Maiken Nedergaard",
year = "2014",
month = "9",
day = "25",
doi = "10.1016/j.brainres.2014.07.029",
language = "English (US)",
volume = "1582",
pages = "211--219",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

TY - JOUR

T1 - Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of Alexander disease

AU - Cotrina, Maria Luisa

AU - Chen, Michael

AU - Han, Xiaoning

AU - Iliff, Jeffrey

AU - Ren, Zeguang

AU - Sun, Wei

AU - Hagemann, Tracy

AU - Goldman, James

AU - Messing, Albee

AU - Nedergaard, Maiken

PY - 2014/9/25

Y1 - 2014/9/25

N2 - 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.

AB - 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.

KW - Astrocyte

KW - Epilepsy

KW - GFAP

KW - Glia

KW - Trauma

UR - http://www.scopus.com/inward/record.url?scp=84907713865&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907713865&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2014.07.029

DO - 10.1016/j.brainres.2014.07.029

M3 - Article

C2 - 25069089

AN - SCOPUS:84907713865

VL - 1582

SP - 211

EP - 219

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -