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Leksell gamma knife lesioning of the rat hippocampus: the relationship between radiation dose and functional and structural damage.
Liscak R, Vladyka V, Novotny J Jr, Brozek G, Namestkova K, Mares V, Herynek V, Jirak D, Hajek M, Sykova E.
Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Czech Republic. Roman.Liscak@homolka.cz
OBJECT: 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.
