Leksell gamma knife lesioning of the rat hippocampus: the relationship between radiation dose and functional and structural damage.
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.
Liscák
Roman
R
Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Czech Republic. Roman.Liscak@homolka.cz
Vladyka
Vilibald
V
Novotný
Josef
J
Brozek
Gustav
G
Namĕstkova
Katerina
K
Mares
Vladislav
V
Herynek
Vít
V
Jirák
Daniel
D
Hájek
Milan
M
Syková
Eva
E
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