CDP-choline at high doses is as effective as i.v. thrombolysis in experimental animal stroke.
Use of thrombolysis in acute ischaemic stroke may be limited by a narrow benefit/risk ratio. Pharmacological inhibition of the ischaemic cascade may constitute an effective and safer approach to stroke treatment. This study compared the effects of high doses of cytidine diphosphate-choline  (CDP-choline; 1000 mg/kg) with recombinant tissue plasminogen activator (rt-PA; 5 mg/kg) in an experimental animal model of embolic stroke. Fifteen rats were embolized in the right internal carotid artery with an autologous clot and were divided into three groups: (1) infarct; (2) intravenous  rt-PA 5 mg/kg 30 minutes post-embolization; and (3) CDP-choline 1000 mg/kg, intraperitoneal, three doses, 30 minutes, 24 hours, and 48 hours post-embolization. Functional evaluation scores were evaluated using Rogers test, lesion volume by haematoxylin and eosin staining, cell death with transferase-mediated  dUTP nick-end labelling, and plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha with enzyme-linked immunosorbent assay. In this study, CDP-choline and rt-PA produced a significant reduction in brain damage considering infarct volume, cell death, and inflammatory cytokines  (tumour necrosis factor-alpha and IL-6) compared with the infarct group. Additionally, CDP-choline significantly decreased infarct volume, cell death, and IL-6 levels with respect to the rt-PA group. From these results, we conclude that high-dose CDP-choline may be an effective treatment for  acute ischaemic stroke even in absence of thrombolysis.
Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neurosciences Area of IdiPAZ (Health Research Institute), Autónoma University of Madrid, Spain. mariagutierrezfdez@hotmail.com
María
M
Gutiérrez-Fernández
María Alonso de
MA
Leciñana
Berta
B
Rodríguez-Frutos
Jaime
J
Ramos-Cejudo
José María
JM
Roda
Exuperio
E
Díez-Tejedor
D000818:Animals; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage*; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D008297:Male; D018697:Nootropic Agents / Q000008:administration & dosage; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage; D016896:Treatment Outcome
D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline; D010959:Tissue Plasminogen Activator