Prostaglandin E 1 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-α (TNF-α)in vitro. We previously reported that TNF-α 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-α 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-α 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-α production at the site of injury. These effects of PGE₁ might at least partly contribute to therapeutic effect on SCI in rats.