Effect of carvedilol on neuronal survival and poly(ADP-ribose) polymerase activity in hippocampus after transient forebrain ischemia.
Carvedilol a beta-adrenoreceptor antagonist with potent antioxidant properties raises high expectations in therapy of ischemia. In this study the effect of carvedilol on neuronal survival after transient forebrain ischemia in gerbils was investigated. The role of poly(ADP-ribose) polymerase (PARP-1) in this process was evaluated. Our data indicated that carvedilol administered subcutaneously in a dose of 7 or 70 mg/kg b.w. directly after 5 min of transient forebrain ischemia protects significant population of neurons in hippocampal area CA1, but has no effect after induction of prolonged 10 min ischemia. Carvedilol significantly decreased PARP activity in hippocampus that was markedly increased after both 15 min and 4 days of reperfusion following 5 min of ischemia. Moreover, carvedilol prevented NAD+ depletion after ischemic-reperfusion insult. These results indicated that carvedilol protects neurons against death and suggested that suppression of PARP activity during reperfusion could be involved in this process.
Strosznajder
Robert P
RP
Department of Respiratory Research, Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego St., 02-106 Warsaw, Poland. roberts@cmdik.pan.pl.
Jesko
Henryk
H
Dziewulska
Jolanta
J
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D008297:Male; D009243:NAD / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011412:Propanolamines / Q000008:administration & dosage*; D015427:Reperfusion Injury / Q000517:prevention & control; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D009243:NAD; D011065:Poly(ADP-ribose) Polymerases