Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons.
BACKGROUND
Inflammation around cell bodies of primary sensory neurons and retinal ganglion cells enhances expression of neuronal growth-associated genes and stimulates axonal regeneration. We have asked if inflammation would have similar effects on corticospinal neurons, which normally show little response to spinal cord injury. Lipopolysaccharide (LPS) was applied onto the pial surface of the motor cortex of adult rats with or without concomitant injury of the corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in the motor cortex was assessed by immunohistochemistry for OX42 (a microglia and macrophage marker). Expression of growth-associated genes c-jun, ATF3, SCG10 and GAP-43 was investigated by immunohistochemistry or in situ hybridisation.


RESULTS
Application of LPS induced a gradient of inflammation through the full depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2 weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had very limited effects on neuronal ATF3 expression. However, many glial cells in the subcortical white matter upregulated ATF3. LPS did not promote sprouting of anterogradely labelled corticospinal axons, which did not grow into or beyond a cervical lesion site.


CONCLUSIONS
Inflammation produced by topical application of LPS promoted increased expression of some growth-associated genes in the cell bodies of corticospinal neurons, but was insufficient to promote regeneration of the corticospinal tract.
Hossain-Ibrahim
M K
MK
Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK. mohammed.hossain-ibrahim@ucl.ac.uk
Rezajooi
K
K
MacNally
J K
JK
Mason
M R J
MR
Lieberman
A R
AR
Anderson
P N
PN
D051700:Activating Transcription Factor 3 / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001370:Axonal Transport; D001710:Biotin / Q000031:analogs & derivatives; D039481:CD11b Antigen; D002352:Carrier Proteins; D002772:Cholera Toxin; D003911:Dextrans; D004660:Encephalitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D016758:Genes, jun; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D006128:Growth / Q000235:genetics*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013266:Stilbamidines
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D039481:CD11b Antigen; D002352:Carrier Proteins; D003911:Dextrans; D005904:Glial Fibrillary Acidic Protein; C509295:ITGAM protein, human; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016755:Proto-Oncogene Proteins c-jun; D013266:Stilbamidines; C512848:Stmn2 protein, rat; C076397:biotinylated dextran amine; C482199:lipopolysaccharide, E coli O55-B5; D001710:Biotin; D002772:Cholera Toxin