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

doi:10.1016/S0014-4886(02)00051-1

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

Institut for Neurovidenskab

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

126 Citationer (Scopus)

Abstract

Udgivelsesdato: 2003-Jun

Originalsprog	Engelsk
Tidsskrift	Experimental Neurology
Vol/bind	181
Udgave nummer	2
Sider (fra-til)	130-148
Antal sider	18
ISSN	0014-4886
DOI	https://doi.org/10.1016/S0014-4886(02)00051-1
Status	Udgivet - 2003

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Adgang til dokumentet

10.1016/S0014-4886(02)00051-1

Citationsformater

Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury. / Penkowa, Milena; Giralt, Mercedes; Lago, Natalia; Camats, Jordi; Carrasco, Javier; Hernández, Joaquin; Molinero, Amalia; Campbell, Iain L; Hidalgo, Juan.

I: Experimental Neurology, Bind 181, Nr. 2, 2003, s. 130-148.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@article{e6cf781074c411dbbee902004c4f4f50,

title = "Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury",

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.",

keywords = "Faculty of Health and Medical Sciences, Animals, Antioxidants, Apoptosis, Astrocytes, Brain Injuries, Central Nervous System, Cerebral Cortex, Disease Models, Gene Targeting, Gliosis, Interleukin-6, Lymphocytes, Macrophages, Transgenic, Oxidative Stress, Wound Healing",

author = "Milena Penkowa and Mercedes Giralt and Natalia Lago and Jordi Camats and Javier Carrasco and Joaquin Hern{\'a}ndez and Amalia Molinero and Campbell, {Iain L} and Juan Hidalgo",

year = "2003",

doi = "10.1016/S0014-4886(02)00051-1",

language = "English",

volume = "181",

pages = "130--148",

journal = "Experimental Neurology",

issn = "0014-4886",

publisher = "Academic Press",

number = "2",

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TY - JOUR

T1 - Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury

AU - Penkowa, Milena

AU - Giralt, Mercedes

AU - Lago, Natalia

AU - Camats, Jordi

AU - Carrasco, Javier

AU - Hernández, Joaquin

AU - Molinero, Amalia

AU - Campbell, Iain L

AU - Hidalgo, Juan

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

KW - Faculty of Health and Medical Sciences

KW - Animals

KW - Antioxidants

KW - Apoptosis

KW - Astrocytes

KW - Brain Injuries

KW - Central Nervous System

KW - Cerebral Cortex

KW - Disease Models

KW - Gene Targeting

KW - Gliosis

KW - Interleukin-6

KW - Lymphocytes

KW - Macrophages

KW - Transgenic

KW - Oxidative Stress

KW - Wound Healing

U2 - 10.1016/S0014-4886(02)00051-1

DO - 10.1016/S0014-4886(02)00051-1

M3 - Journal article

C2 - 12781987

VL - 181

SP - 130

EP - 148

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - 2

ER -