Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury.
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.
Penkowa
Milena
M
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Denmark.
Giralt
Mercedes
M
Lago
Natalia
N
Camats
Jordi
J
Carrasco
Javier
J
Hernández
Joaquin
J
Molinero
Amalia
A
Campbell
Iain L
IL
Hidalgo
Juan
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002490:Central Nervous System / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005615:Freezing; D018390:Gene Targeting; D005911:Gliosis / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*
D000975:Antioxidants; D015850:Interleukin-6