Interleukin-1 beta is required for the early evolution of reactive astrogliosis following CNS lesion.
The CNS response to injury is characterized by the rapid activation of astrocytes in a process known as astrogliosis. The function of reactive astrocytes is controversial, in that both beneficial and detrimental properties are postulated. Identification of the molecules involved in regulating astrogliosis is an important step towards understanding astrocyte functions and establishing suitable conditions for CNS regeneration. We previously reported that inflammatory cytokines are regulators of astrogliosis but the key cytokine involved in initiating astrogliosis was unclear. We describe here that the elevation of glial fibrillary acid protein (GFAP) transcripts follows the very early rise of interleukin (IL)-1beta mRNA in a murine corticectomy model of CNS lesion. Furthermore, the injury-induced upregulation of GFAP mRNA and protein did not occur in mice genetically deficient for IL-1beta compared to wild-type animals. This was correlated with an absence of an increase in GFAP-immunoreactivity (GFAP-ir) in IL-1beta-null mice at 2 and 3 days of injury. However, by 5 to 7 days after the lesion, GFAP-ir was not different between cytokine-deficient and wild-type controls. Functionally, mice lacking IL-1beta exhibited a significant impairment in reformation of the blood-brain barrier (BBB) following corticectomy compared to wild-type controls. These findings suggest that the rapid production of IL-1beta following trauma plays a beneficial role in initiating astrogliosis in an attempt to restore the integrity of the BBB and seal off the wound site.
Herx
L M
LM
Department of Clinical Neurosciences and Oncology, Faculty of Medicine, University of Calgary, Alberta, Canada.
Yong
V W
VW
D000818:Animals; D001812:Blood-Brain Barrier / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis*; D005911:Gliosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007375:Interleukin-1 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000096:biosynthesis
D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D012333:RNA, Messenger