The protective effects of 15-deoxy-delta-(12,14)-prostaglandin J2 in spinal cord injury.
Secondary tissue damage that occurs within days after spinal cord injury contributes significantly to permanent paralysis, sensory loss, and other functional disabilities. The acute inflammatory response is thought to contribute largely to this secondary damage. We show here that 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), a metabolite of prostaglandin D2 (PGD2) that has anti-inflammatory actions, given daily for the first 2 weeks after spinal cord contusion injury in mice, results in significant improvement of sensory and locomotor function. 15d-PGJ2-treated mice also show diminished signs of microglia/macrophage activation, increased neuronal survival, greater serotonergic innervation, and reduced demyelination in the injured spinal cord. These changes are accompanied by a reduction in chemokine and pro-inflammatory cytokine expression. Our results also indicate that 15d-PGJ2 is likely to reduce inflammation in the injured spinal cord by attenuating multiple signaling pathways: reducing activation of NF-kappa B; enhancing expression of suppressor of cytokine signaling1 and reducing the activation of Janus activated Kinase 2.
Kerr
Bradley J
BJ
Centre for Research in Neuroscience, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Girolami
Elizabeth I
EI
Ghasemlou
Nader
N
Jeong
Suh Young
SY
David
Samuel
S
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003711:Demyelinating Diseases / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007155:Immunologic Factors / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007155:Immunologic Factors; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015230:Prostaglandin D2