CDP-choline treatment induces brain plasticity markers expression in experimental animal stroke.
We investigated the effect of CDP-choline on brain plasticity markers expression in the acute phase of cerebral infarct in an experimental animal model. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (pMCAO) and treated or not with CDP-choline (500 mg/kg) daily for 14 days starting 30 min after pMCAO. Functional status was evaluated with Roger's test; lesion volume with magnetic resonance imaging (MRI) and hematoxylin and eosin staining (H&E); cell death with TUNEL; cellular proliferation with BrdU immunohistochemistry; vascular endothelial growth factor (VEGF), synaptophysin, glial fibrillary acidic protein (GFAP) and low-density lipoprotein receptor-related protein (LRP) by immunofluorescence and Western-blot techniques. CDP-choline significantly improved functional recovery and decreased lesion volume on MRI, TUNEL-positive cell number and LRP levels at 14 days. In addition, CDP-choline significantly increased BrdU, VEGF and synaptophysin values and decreased GFAP levels in the peri-infarct zone compared with the infarct group. In conclusion, our data indicate that CDP-choline improved functional recovery after permanent middle cerebral artery occlusion in association with reductions in lesion volume, cell death and LRP expression. In fact, CDP-choline increased cell proliferation, vasculogenesis and synaptophysin levels and reduced GFAP levels in the peri-infarct area of the ischemic stroke.
Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neurosciences Area of IdiPAZ, Health Research Institute, Autónoma University of Madrid, Madrid, Spain.
María
M
Gutiérrez-Fernández
Berta
B
Rodríguez-Frutos
Blanca
B
Fuentes
María Teresa
MT
Vallejo-Cremades
Julia
J
Alvarez-Grech
Mercedes
M
Expósito-Alcaide
Exuperio
E
Díez-Tejedor
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016708:Synaptophysin / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D018697:Nootropic Agents; D016708:Synaptophysin; D042461:Vascular Endothelial Growth Factor A; D003566:Cytidine Diphosphate Choline