Interleukin-1β is required for the early evolution of reactive astrogliosis following CNS lesion

LM Herx, VW Yong - Journal of Neuropathology & Experimental …, 2001 - academic.oup.com
LM Herx, VW Yong
Journal of Neuropathology & Experimental Neurology, 2001academic.oup.com
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 …
Abstract
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)-1β 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-1β compared to wild-type animals. This was correlated with an absence of an increase in GFAP-immunoreactivity (GFAP-ir) in IL-1β-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-1β 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-1β 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.
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