Essential protective roles of reactive astrocytes in traumatic brain injury

D. J. Myer, Gene G Gurkoff, S. M. Lee, D. A. Hovda, Michael V. Sofroniew

Research output: Contribution to journalArticle

366 Citations (Scopus)

Abstract

Astrocytes respond to traumatic brain injury (TBI) by altered gene expression, hypertrophy and proliferation that occur in a gradated fashion in relation to the severity of the injury. Both beneficial and detrimental effects have been attributed to reactive astrocytes, but their roles after brain injury are not well understood. To investigate these roles, we determined the effects on cortical tissue of ablating reactive astrocytes after contusion injury generated by controlled cortical impact (CCI) of different severities in transgenic mice that express a glial fibrillary acidic protein-herpes simplex virus-thymidine kinase transgene. Treatment of these mice with the antiviral agent, ganciclovir, conditionally ablates proliferating reactive astrocytes. Moderate or severe CCI were generated with a precisely regulated pneumatic piston, and forebrain tissue was evaluated using immunohistochemistry and quantitative morphometry. Moderate CCI in control mice triggered extensive and persisting reactive astrogliosis, with most neurons being preserved, little inflammation and an 18% loss of cortical tissue beneath the impact site. Ablation of reactive astrocytes after moderate CCI in transgenic mice caused substantial neuronal degeneration and inflammation, with a significantly greater 60% loss of cortical tissue. Severe CCI in control mice caused pronounced neuronal degeneration and loss of about 88% of cortical tissue that was not significantly altered by ablating reactive astrocytes in transgenic mice. Thus, ablation of dividing reactive astrocytes exacerbated cortical degeneration after moderate CCI, but did not alter cortical degeneration after severe CCI. These findings indicate that the reactive astrocytes play essential roles in preserving neural tissue and restricting inflammation after moderate focal brain injury.

Original languageEnglish (US)
Pages (from-to)2761-2772
Number of pages12
JournalBrain
Volume129
Issue number10
DOIs
StatePublished - Oct 2006

Fingerprint

Astrocytes
Transgenic Mice
Inflammation
Brain Injuries
Ganciclovir
Thymidine Kinase
Traumatic Brain Injury
Contusions
Glial Fibrillary Acidic Protein
Wounds and Injuries
Simplexvirus
Prosencephalon
Transgenes
Hypertrophy
Antiviral Agents
Immunohistochemistry
Gene Expression
Neurons

Keywords

  • Controlled cortical impact
  • Contusion
  • Glial fibrillary acidic protein
  • Inflammation
  • Neural degeneration
  • Reactive astrocytes
  • Transgenic mice
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Myer, D. J., Gurkoff, G. G., Lee, S. M., Hovda, D. A., & Sofroniew, M. V. (2006). Essential protective roles of reactive astrocytes in traumatic brain injury. Brain, 129(10), 2761-2772. https://doi.org/10.1093/brain/awl165

Essential protective roles of reactive astrocytes in traumatic brain injury. / Myer, D. J.; Gurkoff, Gene G; Lee, S. M.; Hovda, D. A.; Sofroniew, Michael V.

In: Brain, Vol. 129, No. 10, 10.2006, p. 2761-2772.

Research output: Contribution to journalArticle

Myer, DJ, Gurkoff, GG, Lee, SM, Hovda, DA & Sofroniew, MV 2006, 'Essential protective roles of reactive astrocytes in traumatic brain injury', Brain, vol. 129, no. 10, pp. 2761-2772. https://doi.org/10.1093/brain/awl165
Myer, D. J. ; Gurkoff, Gene G ; Lee, S. M. ; Hovda, D. A. ; Sofroniew, Michael V. / Essential protective roles of reactive astrocytes in traumatic brain injury. In: Brain. 2006 ; Vol. 129, No. 10. pp. 2761-2772.
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