Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury

Milena Penkowa, Mercedes Giralt, Natalia Lago, Jordi Camats, Javier Carrasco, Joaquin Hernández, Amalia Molinero, Iain L. Campbell, Juan Hidalgo*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

109 Citations (Scopus)

Abstract

The effect of CNS-targeted IL-6 gene expression has been thoroughly investigated in the otherwise nonperturbed brain but not following brain injury. Here we examined the impact of astrocyte-targeted IL-6 production in a traumatic brain injury (cryolesion) model using GFAP-IL6 transgenic mice. This study demonstrated that transgenic IL-6 production significantly increased wound healing following the cryolesion. Thus, at 20 days postlesion (dpl) the GFAP-IL6 mice showed almost complete wound healing compared to litter mate nontransgenic controls. It seems likely that a reduced inflammatory response in the long term could be responsible for this IL-6-related effect. Thus, while in the acute phase following cryolesion (1-6 dpl) the recruitment of macrophages and T lymphocytes was higher in GFAP-IL6 mice, at 10-20 dpl it was significantly reduced compared to controls. Reactive astrogliosis was also significantly increased up to but not including 20 dpl in the GFAP-IL6 mice. Oxidative stress as well as apoptotic cell death was significantly decreased throughout the time period studied in the GFAP-IL6 mice compared to controls. This could be linked to the altered inflammatory response as well as to the transgenic IL-6-induced increase of the antioxidant, neuroprotective proteins metallothionein-I + II. These results indicate that although in the brain the chronic astrocyte-targeted expression of IL-6 spontaneously induces an inflammatory response causing significant damage, during an acute neuropathological insult such as following traumatic injury, a clear neuroprotective role is evident. © 2003 Elsevier Science (USA). All rights reserved.
Original languageEnglish
Pages (from-to)130-148
JournalExperimental Neurology
Volume181
DOIs
Publication statusPublished - 1 Jun 2003

Keywords

  • Apoptosis
  • Inflammation
  • Neurodegeneration
  • Neuroprotection
  • Neurotrauma
  • Oxidative stress
  • Wound healing

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