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Leukemia Inhibitory Factor Augments Neurotrophin Expression and Corticospinal Axon Growth after Adult CNS Injury

Blesch, A. and Uy, H. S. and Grill, R. J. and Cheng, J.-G. and Patterson, P. H. and Tuszynski, M. H. (1999) Leukemia Inhibitory Factor Augments Neurotrophin Expression and Corticospinal Axon Growth after Adult CNS Injury. Journal of Neuroscience, 19 (9). pp. 3556-3566. ISSN 0270-6474. PMCID PMC6782234. doi:10.1523/JNEUROSCI.19-09-03556.1999.

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The cytokine leukemia inhibitory factor (LIF) modulates glial and neuronal function in development and after peripheral nerve injury, but little is known regarding its role in the injured adult CNS. To further understand the biological role of LIF and its potential mechanisms of action after CNS injury, effects of cellularly delivered LIF on axonal growth, glial activation, and expression of trophic factors were examined after adult mammalian spinal cord injury. Fibroblasts genetically modified to produce high amounts of LIF were grafted to the injured spinal cords of adult Fischer 344 rats. Two weeks after injury, animals with LIF-secreting cells showed a specific and significant increase in corticospinal axon growth compared with control animals. Furthermore, expression of neurotrophin-3, but not nerve growth factor, brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor, or ciliary neurotrophic factor, was increased at the lesion site in LIF-grafted but not in control subjects. No differences in astroglial and microglial/macrophage activation were observed. Thus, LIF can directly or indirectly modulate molecular and cellular responses of the adult CNS to injury. These findings also demonstrate that neurotrophic molecules can augment expression of other trophic factors in vivo after traumatic injury in the adult CNS.

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Additional Information:© 1999 Society for Neuroscience. Beginning six months after publication the Work will be made freely available to the public on SfN’s website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license ( Received Nov. 17, 1998; revised Feb. 2, 1999; accepted Feb. 16, 1999. This work was supported by grants from Veterans Affairs, the National Institute of Neurological Disorders and Stroke (NS37083), the National Institute for Aging (NS37083), the American Paralysis Association, National Institutes of Health (NS 20916 to P.H.P.), and the Deutsche Forschungsgemeinschaft (A.B). We express our appreciation to Dr. Silke Thode for providing selected primer sequences.
Funding AgencyGrant Number
Department of Veterans AffairsUNSPECIFIED
American Paralysis AssociationUNSPECIFIED
NIHNS 20916
Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
National Institute of Neurological Disorders and Stroke (NINDS)UNSPECIFIED
Subject Keywords:leukemia inhibitory factor; LIF; gene therapy; corticospinal; spinal cord injury; regeneration; neurotrophic factors
Issue or Number:9
PubMed Central ID:PMC6782234
Record Number:CaltechAUTHORS:20160404-085813345
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Official Citation:Leukemia Inhibitory Factor Augments Neurotrophin Expression and Corticospinal Axon Growth after Adult CNS Injury A. Blesch, H. S. Uy, R. J. Grill, J.-G. Cheng, P. H. Patterson, and M. H. Tuszynski The Journal of Neuroscience, 1 May 1999, 19(9):3556-3566
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65882
Deposited By: Ruth Sustaita
Deposited On:04 Apr 2016 17:50
Last Modified:10 Nov 2021 23:50

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