Therapeutic Effect Of Low-intensity Focused Ultrasound On Non-human Primate Epilepsy Model

BACKGROUND:Epilepsy is one of the most common chronic diseases in the nervous system.For drug-resistant epilepsy,in addition to resection surgery,neuromodulation is also an important method.LIFUS,a non-invasive method of regulating brain activity,has received widespread attention in recent years.The therapeutic effect of LIFUS on animal models of rodent epilepsy has been confirmed.OBJECT:Non-human primate acute epilepsy models were treated by LIFUS stimulation.Transcranial ultrasound stimulation and ultrasound stimulation were used in this study.LIFUS stimulation was first applied to the non-human primate epilepsy models.Furthermore,LIFUS stimulation was promoted to the clinical application of LIFUS.METHODS:In the first stage,the skull above the right frontal cortex of the cynomolgus monkey was removed,and penicillin was injected into the frontal cortex to establish an acute epilepsy model.After 30 minutes of penicillin injection,LIFUS stimulated the frontal cortex.The number of seizures,the duration of seizures,and the duration of seizures were used to evaluate the effect of LIFUS stimulation.The safety of ultrasound stimulation was verified by in vitro temperature test and HE staining.The second part is to study further the effect of transcranial ultrasound stimulation on non-human primate acute epilepsy model.Then a hole was made in the skull above the left frontal cortex of the rhesus monkey,and penicillin was injected through the small hole into the frontal cortex to establish an acute epilepsy model.Thirty minutes after penicillin injection was completed,LIFUS was through the skull to stimulate the frontal cortex.The number of seizures optimized the ultrasound stimulation parameters,and the optimal LIFUS parameters were applied to the rhesus monkey model of epilepsy.Duration and interval between seizures assess the efficacy of transcranial LIFUS treatment.The safety of ultrasound stimulation was verified by in vitro temperature test and magnetic resonance examination.RESULTS:1.Compared with the sham stimulation group,LIFUS(no skull)directly affects the frontal cortex,reduces the number of spikes caused by penicillin,reduces the number of seizures,shortens the duration of seizures,and prolongs the duration of seizures.2.Compared with the sham stimulation group,transcranial LIFUS stimulation of the frontal cortex can also reduce the number of penicillin-induced seizures,shorten the duration of seizures and prolong the duration of seizures.3.Compared with transcranial LIFUS stimulation for 5 minutes,30 minutes,and 60 minutes,the number of seizures was minimal at 15 minutes of ultrasound stimulation.4.It was found in the two-stage study that the temperature increase caused by ultrasonic stimulation did not exceed 1?.5.No obvious brain tissue damage was observed by magnetic resonance examination and HE staining.CONCLUSION:LIFUS stimulates the frontal cortex to treat non-human primate acute epilepsy induced by penicillin.But most of the energy produced by ultrasound is blocked outside the skull.From the perspective of imaging and histology,no damage was found to the cerebral cortex by ultrasound.In general,LIFUS stimulation is a safe and effective neuromodulation method.