Prostaglandin E1 prevents apoptotic cell death in superficial dorsal horn of rat spinal cord.
Neuronal degeneration, distinguished morphologically and biochemically from necrosis, was induced in the dorsal horn of the lumbar spinal cord by chronic constriction of the sciatic nerve in rats. Neuronal apoptosis in the territory of the spinal cord which receives afferent excitatory inputs from the sciatic nerve was confirmed by TUNEL-staining and electrophoresis of genomic DNA. The morphological changes including the appearance of dark neurones, as identified by toluidine-blue staining, were almost completely blocked by 10 microg/kg of the prostaglandin E (EP) receptor agonist lipo-PGE1, incorporating PGE1 in lipid microspheres for chemical stability and targeted delivery, but not by 10 microg/kg of carbacyclin a prostacyclin (IP) receptor agonist. Lipo-PGE1 also blocked the "ladder type" fragmentation of genomic DNA extracted from tissue in the affected area of the spinal cord. Since the regional blood flow in the subfield of the spinal cord was neither influenced by the chronic injury nor by application of the vasodilative prostaglandin, the effect of lipo-PGE1 must have been achieved via another mechanism. These results demonstrate that the neuronal apoptosis in spinal cord induced by sciatic constriction injury is more effectively inhibited by the EP receptor agonist PGE1 than by the IP receptor agonist carbacyclin.
Kawamura
T
T
Central Research Laboratories, The Green Cross Corporation, Osaka, Japan.
Akira
T
T
Watanabe
M
M
Kagitani
Y
Y
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003250:Constriction; D053938:DNA Fragmentation / Q000187:drug effects; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000819:agonists; D018078:Receptors, Prostaglandin E / Q000819:agonists*; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; C026678:carboprostacyclin; D011464:Epoprostenol; D000527:Alprostadil