The Effect Gamma Knife Radiosurgery On Glutamate And Gama-Aminobutyric Acid Levels In The Cerebrospinal Fluid Of Experimenta Epileptic Rats

Establish the lithium-pilocarpine-induced experimental rat model of temporal lobe epilepsy and analysis the early death of induced epileptic ratsOBJECTIVEStudy of the behavioral seizure characteristics, EEG changes and epileptic causes of early death in rats that were lithium-pilocarpine model of temporal lobe epilepsy after epileptic seizures, So as to provide a way and to reduce early mortality of epileptic rats for establishing a stable lithium-pilocarpine model of temporal lobe epilepsy.METHODSThe Wistar rats were randomly divided into saline control group which contains 25 rats, and epilepsy model group which contains 80, Epilepsy model rats were given lithium chloride, atropine sulfate, pilocarpine by intraperitoneal injection to induce status epilepticus(SE), and to terminate seizures by diazepam 1 hour after the injection of continuous. To observe the spontaneous recurrent seizures(SRS) per day thereafter, and record the EEG trace of the rats at awaking before making model, being status epilepticus, six weeks later. So as to record the deaths of epileptic rats in the SE period, quiet period, and chronic phase.RESULTSThe success rate of SE-induced was 92.5%(74/80) in lithium-pilocarpine model of temporal lobe epilepsy rats. After 10-20 days of the silent period, we can observe I-V grade repeated SRS, EEG in the acute phase showed sustained high volatility spikes clustered; and we can record the dissemination of spikes or spike and slow wave in chronic phase. The mortality of induced epileptic rats was 21.62% in SE period,4.06% in silent period,0% in chronic phase. Total mortality rate was 25.68% (19/74). The success rate of epilepsy model was 68.8%(55/80)CONCLUSIONLithium-pilocarpine model of temporal lobe epilepsy epileptic high success rate, After epilepsy induced, the overall mortality rate of epileptic is not high, and is mainly focused on the SE period, is an ideal animal model of temporal lobe epilepsy.Chapter TwoThe effection of glutamate and y-aminobutyric acid in cerebrospinal fluid of rats with temporal lobe epilepsy by low-dose gamma knife irradiationObjectiveResearch the effection of glutamate and y-aminobutyric acid in cerebrospinal fluid of rats with temporal lobe epilepsy by gamma knife, To investigate the mechanism of Gamma Knife radiosurgery treatment of temporal lobe epilepsy, To provide a theoretical basis for clinical practice.MethodThe Wistar rats were divided into saline control group, surgery group, non-surgical group, each 25 rats, To establish a temporal lobe epilepsy model with lithium-pilocarpine, SE-operated rats were given Gamma Knife after 4 weeks, Irradiated target was the left hippocampus, Out Measurement was20Gy, Isodose curve was 80%, To observe the frequency of epileptic seizures in rats at GKS before, GKS after Id, GKS after 2W, GKS after 4W, GKS post-8W respectively, then puncture and collect the CSF at the foramen at GKS after 1d, GKS after 1W, GKS after 2W, GKS after 4W, GKS post-8W respectively, Detect the Glu,GABA content in CSF by joint mass spectrometry Liquid Chromatography.ResultsBehavioral obseevation found the saline control rats without epileptic seizures. After gamma knife irradiation 4W,the number of epileptic seizures in rats of operation group were significantly different from non-surgical group(P=0.000),The seizure frequency in rats with Gamma Knife irradiation 1d,2W later were no significant difference from non-surgical rats(P> 0.05), The cerebrospinal fluid examination results showed that the Glu content in cerebrospinal fluid of operated rats were significant differences from non-operated group after Gamma irradiation induced epileptic rats 1W(P<0.05), and there were difference 2W later,4W later,8W later. Operation group (Glu content of number 709.579nmol/ml) lower than that of non-operation group (Glu content of number 828.620nmol/ml). And the Glu content in cerebrospinal fluid of the surgical rats deceased with time. The GABA levels of the surgical group with 1W irradiation were significant different from non-operated rats(P <0.05), and there was a significant difference at 2W later,4W later,8W later(P= 0.000), Operation group (GABA content of number 221.866nmol/ml) were higher than non-operation group (GABA content of number 159.730nmol/ml)), CSF GABA levels of the operation group increased with time.ConclusionAfter gamma knife irradiation induced epileptic rats, the Glu content in cerebrospinal fluid of epileptic rats decreased, GABA content increased, that prior to the reduced frequency of epileptic seizures in rats. Glu content decreased, GABA content increased in epileptic rats, cause excitatory neurotransmitter and inhibitory neurotransmitter imbalances, Thereby the frequency of epileptic seizures in rats were reduced. The imbalances between excitatory neurotransmitter and inhibitory neurotransmitter may be one of an important mechanism for temporal lobe epilepsy by gamma Knife treatment.