title: Effects of voluntary physical exercise, citicoline, and combined treatment on object recognition memory, neurogenesis, and neuroprotection after traumatic brain injury in rats.
abstract: The biochemical and cellular events that lead to secondary neural damage after traumatic brain injury (TBI) contribute to long-term disabilities, including memory deficits. There is a need to search for single and/or combined treatments aimed at reducing these TBI-related disfunctions. The effects of citicoline and of voluntary physical exercise in a running wheel (3 weeks), alone or in combination, on TBI-related short-term (3 h) and long-term (24 h) object recognition memory (ORM) deficits and on neurogenesis and neuroprotection were examined using a rodent model of TBI (controlled cortical impact injury). Citicoline improved memory deficits at the two times tested, while physical exercise only in the long-term test. Physical exercise had a clear neuroprotective effect as indicated by reduced interhemispheric differences in hippocampal formation and lateral ventricle volumes and in density of mature neurons in the hilus of the dentate gyrus and the perirhinal cortex. Physical exercise also increased cell proliferation and neurogenesis in the granular cell layer of the dentate gyrus. Some degree of neuroprotection of citicoline was suggested by reduced interhemispheric differences in the volume of the hippocampal formation. Contrary to what was expected, the effects of citicoline and physical exercise did not sum up. Further, a negative interference between both treatments was found in several behavioral and histological variables. The promising profiles of both treatments as therapeutic tools in TBI when applied singly underscore the need to perform further works looking for other combined treatment regimens that increase the benefit of each treatment alone.
authors.affiliation: 1 Departament de Psicobiologia i de Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona , Bellaterra, Barcelona, Spain .
authors.forename: Alejandra
authors.initials: A
authors.lastname: Jacotte-Simancas
authors.forename: David
authors.initials: D
authors.lastname: Costa-Miserachs
authors.forename: Margalida
authors.initials: M
authors.lastname: Coll-Andreu
authors.forename: Meritxell
authors.initials: M
authors.lastname: Torras-Garcia
authors.forename: Cesar V
authors.initials: CV
authors.lastname: Borlongan
authors.forename: Isabel
authors.initials: I
authors.lastname: Portell-Cortés
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000188:drug therapy / Q000503:physiopathology* / Q000628:therapy*; D003131:Combined Modality Therapy; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D000066829:Neuroprotection / Q000187:drug effects / Q000502:physiology*; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*
chemical_list: D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline
keywords: citicoline; neurogenesis and neuroprotection; object recognition memory; traumatic brain injury; voluntary physical exercise