Leukemia inhibitory factor is expressed in astrocytes following cortical brain injury

Exp Neurol. 1997 Sep;147(1):1-9. doi: 10.1006/exnr.1997.6536.


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 injury response in LIF knock-out 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 situ hybridization 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 both in vivo and in vitro.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Cerebral Cortex / injuries
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Female
  • Functional Laterality
  • Growth Inhibitors / genetics
  • Growth Inhibitors / metabolism*
  • In Situ Hybridization
  • Interleukin-6*
  • Leukemia Inhibitory Factor
  • Lymphokines / genetics
  • Lymphokines / metabolism*
  • Microglia / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley


  • Growth Inhibitors
  • Interleukin-6
  • Leukemia Inhibitory Factor
  • Lymphokines
  • RNA, Messenger