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Experimental Study On The Animal Model Of Lennox-Gastaut Syndrome

Posted on:2017-12-06Degree:MasterType:Thesis
Country:ChinaCandidate:Q YangFull Text:PDF
GTID:2404330590969502Subject:Surgery
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Part I The performance of electroencephalography and semiology in infant rats suffered status epilepticusObjective To observe the performance of electroencephalography(EEG)and semiology in infant rats who suffered status epilepticus(SE)and estimate whether the features of those rats have something in common with Lennox-Gastaut syndrome(LGS).Methods A total of 40 male Wistar rats were randomly divided into two groups,LGS model group and control group.SE was induced in LGS rats(n=25)by intraperitoneal injection of lithium and pilocarpine.In the control group(n=15),pilocarpine was replaced with normal saline.One week later,all rats were implanted with epidural electrodes for long-term video-EEG monitoring.Results In the LGS group,22 of 25 rats were successfully induced SE and completed video-EEG monitoring.Abnormal EEG patterns of slow spike-and-waves(SSWs)and numbers of epileptic discharges such as spikes,spike and waves,slow waves were observed in all LGS rats.There were four types of seizures recorded.Firstly,atypical absence seizure,which was observed in all rats in the LGS group,was often accompanied by behavioral immobility that normal activities were interrupted by the emergence of SSWs and recovered after disappearance of SSWs.The ictal EEG showed episodes of generalized SSWs with frequency of 1.5-2.5 Hz.The durations of seizure lasted for a few seconds or up to minutes.Secondly,tonic seizure,which was seen in all LGS rats,successively involved eyes opening(during sleep)and staring,pause in movements,sustaining gesture of neck inflexibility,tail hyperextension and limbs rigidity.The ictal EEG showed a brief generalized attenuation of background followed by generalized PFA with frequency of 7-13 Hz.Thirdly,tonic-clonic seizure,which was recorded in 5 of 22 rats,often accompanied by limbs rigidity,limbs clonus,trunk hyperextension and falling.The ictal EEG showed burst of PFA then followed by slow waves.Duration of tonic-clonic seizure was ranged between 60 s and 120 s.Finally,suspicious spasm,which observed only in one LGS rat,associated with sudden jerk of trunk.The ictal EEG showed burst of a sharp wave before behavioral changes.In the control group,all 15 rats performed normally.Conclusion The infant rats suffering from SE had characteristic electroclinical features of Lennox-Gastaut syndrome,including abnormal EEG patterns(SSWs and PFA)and multiple seizure types which accord with the features of LGS.Part Ⅱ The cognitive impairment and alternation of histology and immunohistochemistry in infant rats suffered status epilepticusObjective To observe the cognitive impairment and alternation of histology and immunohistochemistry in infant rats who suffered status epilepticus(SE)and estimate whether the features of those rats have something in common with Lennox-Gastaut syndrome(LGS).Methods A total of 30 male Wistar rats were randomly divided into two groups,LGS model group and control group.SE was induced in LGS rats(n=15)by intraperitoneal injection of lithium and pilocarpine.In the control group(n=15),pilocarpine was replaced with normal saline.Three week later,spatial learning and memory was tested with Morris water maze.After behavioral test,rats were executed for histological(Nissl staining)and immunohistochemical(TUNEL staining)examinations.Results LGS rats exhibited longer escape latencies and swimming distance than control rats(P< 0.05).Also,the LGS rats had more failures than control rats from second testing day to the last(P< 0.05).In the area of DG,neurons stained by Nissl showed normal structures,which had a regular neuron arrangement and round nucleus with a clear outline,were observed both in the control and LGS group.In the area of CA1,LGS rats revealed an abnormal neuron arrangement,concentrated nucleus and neuron degeneration(P< 0.05).TUNEL-positive apoptotic cells were rarely detected both in the control and LGS group in the area of DG.While the number of TUNEL-positive cells in LGS rats was increased in the area of CA1 comparing with the control rats(P< 0.05).Conclusion The infant rats suffering from SE showed cognitive impairment and neurons death which accord with the features of LGS.Part Ⅲ The theoretical deduction and hypothesis of mechanism of Lennox-Gastaut syndromeObjective To hypothesis the potential mechanism of Lennox-Gastuat syndrome.Methods Based on the studies of brain network,we deducted the pathogenesis basis,potential mechanism and treatment targets of LGS.Results The characteristic of brain network during childhood might be the pathogenesis basis of LGS.The potential mechanism of LGS is that the epileptiform activity interacting with the networks to induce an unstable network pattern.The treatment of LGS might seek to reduce network instability.Conclusion LGS could be conceptualized as a network disorder which associated with the function of brain network.
Keywords/Search Tags:Lennox-Gastaut syndrome, Electroencephalography, Seizure, Animal model, Cognitive impairment, Mechanism, Brain network
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