title: Pre-treatment and post-treatment with alpha-tocopherol attenuates hippocampal neuronal damage in experimental cerebral hypoperfusion.
abstract: Alpha-tocopherol, a potent antioxidant, has been widely investigated as a dietary supplement with which to reduce the risk of atherosclerosis, and has recently been considered as a potential supplement to moderate oxidative neuronal damage in Alzheimer's disease patients. Since alpha-tocopherol appears beneficial in vascular and neurodegenerative disorders, we set out to identify its neuroprotective action in a rat model of chronic cerebral hypoperfusion-induced brain injury. The bilateral common carotid arteries of male Wistar rats were permanently occluded (2VO). Sham-operated animals served as controls. Half of the animals were pre- or post-treated repeatedly with alpha-tocopherol (5x100 mg/kg daily, i.p.), the other half receiving only soybean oil, the alpha-tocopherol vehicle. One week after the onset of 2VO, the spatial learning capacity of the animals was assessed in the Morris water maze. After testing, hippocampal slices were stained with cresyl violet in order to examine the pyramidal cell layer integrity. The density of microtubule-associated protein-2 (MAP-2)-positive dendrites and the OX-42-labeled microglial activation level were determined immunocytochemically. Finally, alpha-tocopherol was determined in the peripheral tissues, blood and brain. Alpha-tocopherol moderated the 2VO-induced learning impairment. The various forms of alpha-tocopherol treatment, and particularly the post-treatment, prevented the 2VO-induced pyramidal cell death and the activation of microglia in the hippocampus CA1 region, and the degeneration of MAP-2-positive dendrites in the CA3 region. The alpha-tocopherol concentration was elevated in the peripheral tissues and the blood, but not in the brain. The data indicate that alpha-tocopherol, particularly when administered as post-treatment, is neuroprotective in chronic cerebral hypoperfusion.
authors.affiliation: Department of Physiology, School of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Anita
authors.initials: A
authors.lastname: Annaházi
authors.forename: Eva
authors.initials: E
authors.lastname: Mracskó
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Süle
authors.forename: Eszter
authors.initials: E
authors.lastname: Karg
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: Ferenc
authors.initials: F
authors.lastname: Bari
authors.forename: Eszter
authors.initials: E
authors.lastname: Farkas
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017536:Carotid Artery, Common / Q000601:surgery; D016923:Cell Death / Q000187:drug effects; D002560:Cerebrovascular Circulation; D002908:Chronic Disease; D003712:Dendrites / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007858:Learning / Q000187:drug effects; D008026:Ligation; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects; D014018:Tissue Distribution; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D024502:alpha-Tocopherol