Reduction of spinal cord injury by administration of iloprost, a stable prostacyclin analog.
To investigate whether iloprost, a stable analog of prostacyclin, is useful for the prevention of posttraumatic spinal cord injury, we examined its effects on compression trauma-induced spinal cord injury in rats. Spinal cord injury was induced by applying a 20-g weight for 20 minutes to the spinal cord at the level of T-12, resulting in motor disturbances in the hindlimbs. These motor disturbances, evaluated using Tarlov's index, were markedly attenuated in rats with nitrogen mustard-induced leukocytopenia. Administration of iloprost also attenuated the motor deficits. Histological examination revealed that intramedullary hemorrhages observed 24 hours after trauma were significantly attenuated in leukocytopenic animals and in animals that received iloprost. The accumulation of leukocytes at the site of trauma, evaluated by measuring tissue myeloperoxidase activity, significantly increased with time following the trauma, peaking at 3 hours postinjury. Spinal cord myeloperoxidase activity in sham-operated animals did not increase postoperatively. Leukocyte depletion and administration of iloprost reduced the accumulation of leukocytes in the damaged spinal cord segment 3 hours posttrauma. These findings indicate that iloprost attenuates motor disturbances induced by spinal cord trauma and that its therapeutic efficacy can be partly explained by its inhibition of leukocyte accumulation at the traumatized site.
Taoka
Y
Y
Department of Laboratory Medicine, Kumamoto University Medical School, Kumamoto and Naruo Orthopedic Hospital, Japan.
Okajima
K
K
Uchiba
M
M
Murakami
K
K
Harada
N
N
Johno
M
M
Naruo
M
M
Okabe
H
H
Takatsuki
K
K
D000818:Animals; D011464:Epoprostenol / Q000031:analogs & derivatives*; D016285:Iloprost / Q000627:therapeutic use*; D007970:Leukopenia / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008466:Mechlorethamine; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D014949:Wounds, Nonpenetrating / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D008466:Mechlorethamine; D011464:Epoprostenol; D009195:Peroxidase; D016285:Iloprost