title: Prostaglandin E1 reduces compression trauma-induced spinal cord injury in rats mainly by inhibiting neutrophil activation.
abstract: Prostaglandin E1 (PGE1), a potent vasodilator, was recently reported to inhibit both neutrophil activation and monocytic production of tumor necrosis factor-alpha (TNF-alpha) in vitro. We previously reported that TNF-alpha was critically involved in the development of motor disturbances by increasing the accumulation of neutrophils at the site of injury in rats subjected to compression trauma-induced spinal cord injury. Therefore, it is possible that PGE1 reduces motor disturbances by inhibiting neutrophil activation in rats subjected to spinal cord injury. We examined this possibility in a rat model of spinal cord injury (SCI). Motor disturbances induced by spinal cord compression were evaluated using the inclined plane test, and footprint analysis. Accumulation of neutrophils at the site of trauma was evaluated by measuring tissue myeloperoxydase (MPO) activity. Tissue levels of TNF-alpha were determined using an enzyme-linked immunosorbent assay. Motor disturbances induced by spinal cord compression were significantly attenuated in rats administered PGE1. A histological examination revealed that intramedullary hemorrhages, observed 24 h after trauma, were markedly reduced in animals administered PGE1. Increases in the tissue levels of TNF-alpha and MPO activity in the damaged segment of spinal cord were significantly inhibited in animals that had received PGE1. These observations suggested that PGE1 reduces motor disturbances by inhibiting neutrophil activation directly or indirectly through the inhibition of TNF-alpha production at the site of injury. These effects of PGE1 might at least partly contribute to therapeutic effect on SCI in rats.
authors.affiliation: Department of Orthopedic Surgery, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Naruo
authors.forename: Kenji
authors.initials: K
authors.lastname: Okajima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taoka
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Uchiba
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okabe
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Takagi
mesh_terms: D000527:Alprostadil / Q000627:therapeutic use*; D000818:Animals; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018375:Neutrophil Activation / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014949:Wounds, Nonpenetrating / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D009195:Peroxidase; D000527:Alprostadil