Role of prostacyclin in the development of compression trauma-induced spinal cord injury in rats.

We investigated the role of prostacyclin (PGI(2)) in the development of compression trauma-induced spinal cord injury (SCI) in rats. When measured after induction of SCI, tissue levels of 6-keto-PGF(1), a stable PGI(2) metabolite, thromboxane B(2) (TXB(2)), a stable metabolite of thromboxane A(2), myeloperoxidase (MPO) activity, and tumor necrosis factor (TNF) in the injured spinal cord segment were significantly increased, peaking at 2, 3, and 4 h after induction of SCI, respectively. Subcutaneous administration of indomethacin (IM), a non-selective cyclooxygenase (COX) inhibitor, completely inhibited increases in tissue levels of 6-keto-PGF(1) and TXB(2), while administration of NS-398, a selective inhibitor of COX-2, did not affect these increases.

Antithrombin reduces compression-induced spinal cord injury in rats.

Antithrombin (AT), a natural anticoagulant, has been shown to exert anti-inflammatory activity by promoting the endothelial production of prostaglandin I2 (PGI2), thereby reducing tissue injury. To examine whether AT prevents post-traumatic spinal cord injury (SCI), a pathologic condition in which activated neutrophils are critically involved, we tested the effect of AT on SCI induced by compression trauma in rats. Intravenous administration of AT, either before or after the induction of SCI, significantly reduced SCI-related motor disturbances in these animals.

Prostaglandin E1 reduces compression trauma-induced spinal cord injury in rats mainly by inhibiting neutrophil activation.

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.