@article{2996049,
    title = "Effects of AraC treatment on motor coordination and cerebellar cytoarchitecture in the adult rat. A possible protective role of NAC",
    author = "Koros, C. and Papalexi, E. and Anastasopoulos, D. and Kittas, C. and Kitraki, E.",
    journal = "NeuroToxicology",
    year = "2007",
    volume = "28",
    number = "1",
    pages = "83-92",
    issn = "0161-813X",
    doi = "10.1016/j.neuro.2006.07.016",
    keywords = "acetylcysteine;  calbindin;  cytarabine;  water, animal experiment;  animal model;  article;  behavior;  behavior disorder;  cerebellum;  cerebellum disease;  cognition;  controlled study;  cytoarchitecture;  gait;  immunohistochemistry;  learning;  locomotion;  male;  molecular biology;  motor coordination;  neurofilament;  neurotoxicity;  nonhuman;  priority journal;  Purkinje cell;  rat;  swimming;  velocity, Acetylcysteine;  Animals;  Antimetabolites, Antineoplastic;  Calcium;  Cerebellum;  Cognition;  Cytarabine;  Cytoskeleton;  Dose-Response Relationship, Drug;  Immunohistochemistry;  Male;  Maze Learning;  Mice;  Musculoskeletal Equilibrium;  Neurofilament Proteins;  Neuroprotective Agents;  Psychomotor Performance;  Rats;  Rats, Wistar;  Space Perception;  Walking, Animalia;  Rattus;  Rattus norvegicus;  Rodentia",
    abstract = "Intact cerebellum cytoarchitecture and cellular communication are indispensable for successful motor coordination and certain forms of memory. Cytosine arabinoside (AraC), often used as an anti-neoplastic agent in humans, can have cerebellum-targeting adverse effects. In order to characterize the nature of AraC-induced cerebellar lesions in an adult rodent model, we have administered AraC (400 mg/kg b.w., i.p.) in adult male Wistar rats for 5 days. The animals' walking pattern, motor coordination, locomotion, spatial navigation and cognition were evaluated, along with neurofilament- and calbindin-like distribution in the cerebellum. AraC-treated rats demonstrated a disturbed walking pattern and a reduced ability of motor learning and coordination, indicative of a mild cerebellar deficit. Although the general locomotion and spatial cognition of AraC-treated rats was not significantly altered, their navigation into the water, in terms of swimming velocity, was irregular, compared to vehicle-treated animals. Neurofilament-like immunostaining was reduced in the molecular cerebellar layer, while calbindin D 28 kDa levels were increased in Purkinje neurons, following AraC treatment. Administration of the antioxidant N-acetylcysteine (NAC) (200 mg/kg b.w., p.o.), for 14 days (prior to and during AraC treatment) largely prevented the AraC-induced behavioral deficits. Our in vivo model of neurotoxicity provides data on the AraC-induced behavioral and cellular alterations concerning the adult rat cerebellum. Furthermore, it provides evidence of a possible neuroprophylactic role of the antioxidant N-acetylcysteine in this model of chemotherapy-induced toxicity. © 2006 Elsevier Inc. All rights reserved."
}