title: Effects of citicoline used alone and in combination with mild hypothermia on apoptosis induced by focal cerebral ischemia in rats.
abstract: The effects of citicoline used either alone or in combination with hypothermia on the suppression of apoptotic processes after transient focal cerebral ischemia were investigated. Middle cerebral artery occlusion (MCAo) was performed for 2 hours on Sprague-Dawley (SD) rats using intraluminal thread insertion. The treatment groups were as follows: Group 1, sham-operated; Group 2, saline; Group 3, citicoline (400mg/kg intraperitoneal.); Group 4, hypothermia (34+/-1 degrees C); Group 5, citicoline+hypothermia. All rats were reperfused for 24 hours, and after sacrifice and transcardiac perfusion, immunohistochemical studies were performed for markers of apoptosis. In Group 2, the Bcl-2 immunostaining score (mean+/-standard deviation, 0.71+/-0.75) was lower compared to Groups 3, 4 and 5 (2.33+/-0.81; 3.00+/-0.00; 2.20+/-0.83; p<0.05). There was higher expression of caspase-3 proteins in Group 2 (2.28+/-0.95) compared to Group 5 (1.50+/-0.83; p<0.05). Bax proteins were also increased in Group 2 (1.85+/-1.06) compared to Group 5 (0.40+/-0.54) and in Group 4 (2.00+/-0.00) compared to Group 5 (0.40+/-0.54; p<0.05). Significant differences in caspase-9 immunostaining scores were found in Group 2 (2.29+/-0.96) compared to Group 5 (0.20+/-0.44) (p<0.05); Group 3 (1.00+/-0.70) compared to Group 5 (0.20+/-0.44; p<0.05); and Group 4 (3.00+/-0.00; p<0.05) compared to Group 5 (0.40+/-0.54; p<0.05). Thus by suppressing apoptotic processes citicoline with hypothermia is more effective than either used alone in ameliorating cerebral damage after transient focal ischemia.
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Sahin
authors.forename: T
authors.initials: T
authors.lastname: Alkan
authors.forename: S G
authors.initials: SG
authors.lastname: Temel
authors.forename: K
authors.initials: K
authors.lastname: Tureyen
authors.forename: S
authors.initials: S
authors.lastname: Tolunay
authors.forename: E
authors.initials: E
authors.lastname: Korfali
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D020520:Brain Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D007036:Hypothermia, Induced / Q000379:methods*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline