title: Leksell gamma knife lesioning of the rat hippocampus: the relationship between radiation dose and functional and structural damage.
abstract: OBJECTIVE
  The goals of the study were to determine at what dosage and after what interval impairment of hippocampal function occurs after Leksell gamma knife radiosurgery (GKS) of the rat hippocampus and to assess the associated structural changes.
  
  
  METHODS
  Long-Evans rats were irradiated with maximum doses of 25, 50, 75, 100, and 150 Gy, and four 4-mm isocenters were used to cover the hippocampus bilaterally. The impairment of hippocampal function, which is associated with a loss of memory, was measured by testing the impairment of the rats' orientation in a Morris water maze. Changes in the irradiated tissue were measured using magnetic resonance imaging (Bruker 4.7/20 experimental spectrometer). The data were compared with histologically demonstrated changes. Significantly higher incidences of edema, necrosis, and behavioral changes were observed following administration of doses higher than 50 Gy. No edema, necrosis, or behavioral changes were observed when doses were 25 Gy.
  
  
  CONCLUSIONS
  It would seem that rats can be used for experiments involving the induction of complex brain lesions by using four 4-mm isocenters. Testing retention memory for behavioral changes after bilateral GKS of the whole hippocampus proved insensitive; acquisition memory should be tested to assess functional changes of hippocampus. Significantly higher incidences of edema, necrosis, and behavioral changes were observed for doses higher than 50 Gy. There seems to be a therapeutic window during which doses may affect epilepsy without impairing the memory of the rat.
authors.affiliation: Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Czech Republic. Roman.Liscak@homolka.cz
authors.forename: Roman
authors.initials: R
authors.lastname: Liscák
authors.forename: Vilibald
authors.initials: V
authors.lastname: Vladyka
authors.forename: Josef
authors.initials: J
authors.lastname: Novotný
authors.forename: Gustav
authors.initials: G
authors.lastname: Brozek
authors.forename: Katerina
authors.initials: K
authors.lastname: Namĕstkova
authors.forename: Vladislav
authors.initials: V
authors.lastname: Mares
authors.forename: Vít
authors.initials: V
authors.lastname: Herynek
authors.forename: Daniel
authors.initials: D
authors.lastname: Jirák
authors.forename: Milan
authors.initials: M
authors.lastname: Hájek
authors.forename: Eva
authors.initials: E
authors.lastname: Syková
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000473:pathology; D004307:Dose-Response Relationship, Radiation; D006624:Hippocampus / Q000473:pathology* / Q000528:radiation effects / Q000601:surgery*; D008279:Magnetic Resonance Imaging; D018782:Maze Learning; D008568:Memory; D009336:Necrosis; D011833:Radiation Injuries, Experimental / Q000473:pathology*; D016634:Radiosurgery / Q000009:adverse effects*; D051381:Rats; D020318:Rats, Long-Evans