Delayed treatment with rolipram protects against neuronal damage following global ischemia in rats.
In this study the effect of post-treatment with rolipram, an inhibitor of cAMP phosphodiesterase, on neuronal damage following global ischemia was evaluated. Global cerebral ischemia was induced in male Wistar rats by four-vessel occlusion for 20 minutes. Rolipram was administered 6 hours after onset of ischemia and thereafter the following 7 days daily once at a dose of 0.3 or 3.0 mg/kg intraperitoneally. Four weeks after ischemia the amount of intact neurons in the hippocampus and in the striatum was assessed following perfusion fixation. The ischemia-induced neuronal damage in the CA1 sector of the hippocampus and in the striatum was reduced by rolipram at either dose. The present results show that treatment with rolipram reduces ischemic neuronal damage at a therapeutic window of 6 hours.
Block
F
F
Department of Neurology RWTH Aachen, Germany.
Tondar
A
A
Schmidt
W
W
Schwarz
M
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000096:biosynthesis; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007274:Injections, Intraperitoneal; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram; D013997:Time Factors
D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D020889:Rolipram