Protection of rat spinal cord against contusion injury by new prostaglandin derivatives.
Two prostaglandin oligomeric compounds, an acid-form compound and an ester-form compound, were synthesized from alprostadil (prostaglandin E1). They were found to provide significant protection to the rat spinal cord against contusion injury. After laminectomy at the T-11 segment of the spinal cord, a weight drop (10 g x 5 cm) caused a "dynamic" injury. The degree of recovery was estimated by several neurologic deficit indices; the Tarlov score, inclined plane test and hot plate test. In the control group (no drug), animals were still paralyzed 4 weeks after injury (Tarlov score 1 to 2). By administering these prostaglandin oligomers, either pre-injury (30 min before injury; one dose of 6 mg/kg i.p.) or post-injury (3 doses, each of 6 mg/kg i.p. at 30 min, 6 h, and 12 h after injury), the Tarlov scores recovered to 3.5 to 4.5 by 4 weeks, and animals were able to either support body weight or to walk with a slight deficit. Although both acid- and ester-forms of the compound demonstrated efficacy, the ester-form provided greater protection to the spinal cord. Other neurologic deficit indices also supported these observations.
Ohnishi
S T
ST
Membrane Research Institute, Philadelphia, PA.
Barr
J K
JK
Katagi
C
C
Katsuoka
M
M
D000818:Animals; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011465:Prostaglandins, Synthetic / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000517:prevention & control*
D011465:Prostaglandins, Synthetic