CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia.
To estimate protective potential of citicoline in a model of birth asphyxia, the drug was given to 7-day old rats subjected to permanent unilateral carotid artery occlusion and exposed for 65 min to a hypoxic gas mixture. Daily citicoline doses of 100 or 300 m/kg, or vehicle, were injected intraperitoneally for 7 consecutive days beginning immediately after the end of the ischemic-hypoxic insult, and brain damage was assessed by gross zorphology score and weight deficit two weeks after the insult. Caspase-3, alpha-fodrin, Bcl-2, and Hsp70 levels were assessed at 0, 1, and 24 h after the end of the hypoxic insult in another group of rat pups subjected to the same insult and given a single dose of 300 m/kg of citicoline or the vehicle. Citicoline markedly reduced caspase-3 activation and Hsp70 expression 24 h after the insult, and dose-dependently attenuated brain damage. In the context of the well-known excellent safety profile of citicoline, these data suggest that clinical evaluation of the efficacy of the drug in human birth asphyxia may be warranted.
Fiedorowicz
Michał
M
Department of Experimental Pharmacology, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. mfied@cmdik.pan.pl.
Makarewicz
Dorota
D
Stańczak-Mrozek
Kinga I
KI
Grieb
Paweł
P
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001238:Asphyxia Neonatorum / Q000188:drug therapy* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism; D007231:Infant, Newborn; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013049:Spectrin
D002352:Carrier Proteins; D053148:Caspase 3; D003566:Cytidine Diphosphate Choline; D018840:HSP70 Heat-Shock Proteins; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D013049:Spectrin; C505410:Casp3 protein, rat