Establishment And Evaluation Of A Rhesus Monkey Model Of Chronic Temporal Lobe Epilepsy

BACKGROUND:As one of the most common type of epilepsy syndrome,temporal lobe epilepsy struck lots of researchers and a bulk of studies have been conducted base on animal models of epilepsy.However,when review the previous studies about establishment of epilepsy model,we found even use the same chemovulsant procedures,different species of animal have different sensitivities and could induce different outcome.For instance,the rats,always induced generalized convulsive seizures within 1 h after the administration of kainic acid.On contrary,mice and guinea pig show minor behavioral seizures which would missed without EEG monitoring.Since these differences were probably attributed to their intrinsic difference of brain anatomy,i may worthwhile to develop a large non-human primate animal model for further research in field of epilepsy.To date,only several non-human primate models have been developed in some laboratories,and a detailed description of chronic SRSs is still lacking.For this,we intend to develop a rhesus monkey model through a modified method of intracerebral KA injection.Specifically,an ommaya divice was previously implanted using which allows delivery of KA into amygdala repetitively.According to the features of monkeys' behavioral and electrical change,we believe a rhesus monkey model of chronic temporal lobe epilepsy have been developed successfully.OBJECT:As rodents are not suitable for comprehensive electroencephalogram(EEG)investigation via scalp or subdural electrodes recording because of their very small head,a larger primate model that closely recapitulates symptoms of patients with TLE is needed,and here we describe a rhesus monkey model resembling chronic TLE.METHODS:Stereotactic surgery:Implantation of Ommaya device targeting into right amygdala.Then Intra-amygdala KA injections were performed with video EEG monitoring.If no IEDs and seizures catched by EEG monitoring after KA injection,the injection procedure was repeated again two weeks later.Otherwise,only the video EEG recording was performed.Two of six KA-treated animals had subdural electrodes implanted after IEDs and/or seizures were recorded.Intracranial EEG recordings were performed intermittently throughout the experiment.RESULTS:During KA injection,animals displayed no obvious abnormal behavior or suspicious paroxysmal discharges.In the chronic period,all animals showed IEDs in scalp-EEG recordings.Furthermore,seizures in two animals showed similar evolving patterns.There were no obvious convulsive symptoms were found during ictal discharges.Animals displayed either staring or looking around with unchanged posture.Occasionally,the above abnormal behaviors were interrupted by mouth movements such as licking and swallowing.Scalp EEG recordings:the seizure onset indicated that was originating from right temporal lobe region,then almost all recording electrodes showed generalized irregular fast low amplitude activities.As seizures developed,EEG discharges evolved into regular spike rhythms with increasing amplitude and frequency.Subsequently,spike rhythms evolved into less regular and slower patterns and either kept an irregular pattern or evolved into regular patterns.In the later stage,slow waves become evident and a typical complex of spike and slow wave rhythms were found.In other montages,however,because of the attenuation of the skull and scalp,only components of slow waves were displayed.Finally,abnormal EEG activities ended abruptly and returned to normal background EEG activities.Typically,EEG recordings indicated IEDs as spikes with or without slow waves lasting less than three seconds in right temporal region.Intracranial EEG recording:In the early stage of recording,local,typical spike with or without a long lasting wave appeared in the right temporal lobe regions.However,in later recordings(a minimum interval of two weeks),both the right temporal and contralateral brain region showed epileptiform discharge independently,indicating a possible mirror focus.CONCLUSION:Monkeys developed spontaneous recurrent seizures(SRSs)that showed little motor clinical signs but symptoms mimicking temporal lobe absence appeared several weeks after KA injection.What is more,in later stage,subdural EEG recording showed contralateral interictal spikes,which further confirm epilepsy is a constantly evolving phenomenon.