Leukemia Inhibitory Factor Is Expressed in Astrocytes Following Cortical Brain Injury

Abstract

The neuropoietic cytokine leukemia inhibitory factor (LIF) can act as a trophic factor, enhancing neuronal survival, and as a differentiation factor altering neuronal and glial gene expression. LIF also plays a role in the response to injury of the peripheral nervous system, as indicated by an increase in the amount of its mRNA within nonneuronal cells following nerve damage and lack of neuronal injury response in LIF knockout mice. To determine if LIF is regulated after injury to the central nervous system, we surgically lesioned the cortex in adult rat brain. Using a quantitative RNAse protection assay, we find that LIF mRNA increases 30-fold following injury. The amount of this transcript goes up within 6 h after injury, reaches a peak at 24 h and returns to baseline by 7 days postlesion.In situhybridization analysis reveals LIF transcript-containing cells scattered throughout the ipsilateral cortex close, but not immediately adjacent to the lesion site. Double-labeling with a variety of antibodies reveals that LIF mRNA is induced in GFAP-positive astrocytes as well as in a small number of microglial cells. The striking induction of LIF transcripts in glia suggests that this cytokine may play a key injury–response role in the CNS as it does in the PNS, where LIF has been demonstrated to regulate neuropeptide expression bothin vivoandin vitro.