Experimental Studies Of Gamma Knife Surgery In The Kainic Acid-induced Model Of Temporal Lobe Epilepsy In Rats

Objective:Temporal lobe epilepsy(TLE) is the most common type of refractory epilepsy.The author sought to assess the effects of Gamma Knife surgery(GKS) at different dose levels using KA-induced model of temporal lobe epilepsy in rats. Methods:Animal model of TLE was successfully created by stereotactic injection of kainic acid into the Sprague-Dawley rat hippocampus.After epilepsy was confirmed by observation of the seizure pattern and by using etectroencephalography(EEG). Epileptic rats were divided into two experimental groups:Behavioral study experiment(10 animals×4 groups):a peripheral dose of 12,24,36 Gy was administered using a 4-mm collimator with Leksell Gamma Knife on the 15th day after injection of KA.Control animals were subjected to the-same seizure-inducing stimulus but underwent a sham treatment instead of gamma irradiation.Spontaneous recurrent seizures frequencies of different group were studied for 6-hour per week subsequently and persisted for the duration of monitoring (6 weeks).Caspase-3 expression study experiment(8 animals×3 groups and 8 normal rats for controls):a peripheral dose of 12,24 Gy was administered using a 4-mm collimator with Leksell Gamma Knife 48 hours after injection of KA.KA- & normal-control animals were subjected to a sham treatment instead of gamma irradiation.At 2 hr,4 hr,24 hr and 72 hr following GKS,animals were sacrificed by perfusion with Polyoxymethylene respectively.Slices of the hippocampus were prepared and then the examined for expression of activated caspase-3 were indicated using immunehistochemical method.Results:For the behavioral study team:Four weeks after GKS,the frequency of seizures was markedly reduced in rats for each radiosurgically treated group(p＜0.05). A significant reduction was noted between 36Gy and 12Gy group 3 weeks after GKS (p＜0.05),and so does the 24Gy group on the 5th week(p＜0.05).There were no significant difference between 24 Gy and 36 Gy group at any time point of study (p＜0.05).For the caspase-3 expression study team:Catalytically active caspase-3 was detected at the highest level 2 hr following GKS treatment in the KA-control group,which was decreased gradiently thereafter to a higher level.While,few activated caspase-3 expression neurons were detected in the normal control group at any time.The expression of activated caspase-3 neurons continues up to a peak at 4 hr in both GKS treated group and then decrease sharply,and the expression level in each study point were lower than in the KA-control group.Conclusions:The rat model model of temporal lobe epilepsy could be established successfully by KA injection in the hippocampus CA3 area,which closely mimic the clinical manifestations of TLE in humans.Gamma knife radiosurgery could perform dose- and time-related control of epilepsy without causing subsequent behavioral impairment in KA rat model.The increased number of caspase-3-positive cells in KA rat model could be reduced significantly with low dose gamma knife radiosurgery. The results provide rational support for the utility of GKS as a therapeutic strategy for treating epilepsy in KA rat model,which may be caused by prevention of apoptosis.