title: Effects of cerebrolysin administration on oxidative stress-induced apoptosis in lymphocytes from CADASIL patients.
abstract: Cerebrolysin (Cere) is a peptidergic nootropic drug with neurotrophic properties which has been used to treat dementia and sequelae of stroke. Use of Cere prevents nuclear structural changes typical of apoptosis and significantly reduces the number of apoptotic cells after several apoptotic stimuli. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disease caused by mutations of the Notch3 gene encoding the Notch3 protein. Notch3 is involved in the regulation of apoptosis, modulating Fas-Ligand (Fas-L)- induced apoptosis. The aim of this study was to evaluate the in vitro protective effects of Cere against oxidative stress-induced apoptosis in cells from CADASIL patients. We used peripheral blood lymphocytes (PBLs) from 15 CADASIL patients (age range 34-70 years); 2-deoxy-D-ribose (dRib), a highly reducing sugar, was used as paradigm pro-apoptotic stimulus. Apoptosis was analyzed by flow cytometry and fluorescence microscopy. Administration of Cere to PBLs from CADASIL patients cultured under standard conditions had no effect on the percentage of apoptotic cells. Administration of Cere to PBLs cultured with dRib caused a significant decrease in apoptosis after 48 h of culture in only 5 patients, whereas in the other 10 patients, Cere treatment was not associated with any significant difference in the percentage of apoptosis. This result showed a protective effect of Cere against oxidative stress-induced apoptosis only in 30 % of the CADASIL patients, suggesting that the Notch3 gene probably does not influence the anti-apoptotic properties of Cere in vitro.
authors.affiliation: Department of Neurological, Neurosurgical and Behavioural Sciences, University of Siena, Policlinico "Le Scotte", V.le Bracci, 2, 53100 Siena, Italy. formichi@unisi.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Formichi
authors.forename: Elena
authors.initials: E
authors.lastname: Radi
authors.forename: Carla
authors.initials: C
authors.lastname: Battisti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Maio
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dotti
authors.forename: Dafin
authors.initials: D
authors.lastname: Muresanu
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000008:administration & dosage*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D046589:CADASIL / Q000188:drug therapy / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects*; D012266:Ribose / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000596:Amino Acids; D017304:Annexin A5; D018696:Neuroprotective Agents; C006952:cerebrolysin; D012266:Ribose; D020169:Caspases