Gene expression profiling of acute spinal cord injury reveals spreading inflammatory signals and neuron loss.
We have completed the first large-scale gene expression study of acute spinal cord injury (SCI) in rat. Oligonucleotide microarrays containing 1,200 gene-specific probes were used to quantify mRNA levels, relative to uninjured controls, in spinal cords injured using a standard contusion model. Our results revealed a marked loss of neuron-specific mRNAs at the injury site. The surviving cells showed a characteristic inflammatory response that started at the injury site and spread to the distal cord. Changes in several mRNA levels were associated with putative regenerative responses in the spinal cord. Notably, phosphodiesterase 4, nestin, glia-derived neurite promoting factor, and GAP-43 mRNAs increased significantly. Other mRNAs clustered temporally and spatially with these regeneration-associated genes. Thus we have described global patterns of gene expression following acute SCI, and we have identified targets for future study and possible therapeutic intervention.
Carmel
J B
JB
W. M. Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway 08854, USA.
Galante
A
A
Soteropoulos
P
P
Tolias
P
P
Recce
M
M
Young
W
W
Hart
R P
RP
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002470:Cell Survival; D016000:Cluster Analysis; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004195:Disease Models, Animal; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009187:Myelitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012038:Regeneration / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism* / Q000473:pathology
D019922:GAP-43 Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D012333:RNA, Messenger; C049173:glia-derived neurite-promoting factor; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4