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Non-invasive, neurotoxic surgery reduces seizures in a rat model of temporal lobe epilepsy

Highlights•Blood-brain barrier (BBB) was opened in a transient and focal manner through focused ultrasound combined with microbubbles•A neurotoxin (Quinolinic Acid: QA) normally impermeable to BBB gained access to targeted areas in brain, destroyed neurons•Animals with temporal lobe epilepsy untreated or treated without QA exhibited stable seizure frequencies•Animals treated targeting the intermediate-temporal aspect hippocampus exhibited substantial seizure reductions•Animals treated targeting both the septal and intermediate-temporal aspects of the hippocampus showed status epilepticusAbstractSurgery can be highly effective for treating certain cases of drug resistant epilepsy. The current study tested a novel, non-invasive, surgical strategy for treating seizures in a rat model of temporal lobe epilepsy. The surgical approach uses magnetic resonance-guided, low-intensity focused ultrasound (MRgFUS) in combination with intravenous microbubbles to open the blood-brain barrier (BBB) in a transient and focal manner. During the period of BBB opening, a systemically administered neurotoxin (Quinolinic Acid: QA) that is normally impermeable to the BBB gains access to a targeted area in the brain, destroying neurons where the BBB has been opened. This strategy is termed Precise Intracerebral Non-invasive Guided Surgery (PING). Spontaneous recurrent seizures induced by pilocarpine were monitored behaviorally prior to and after PING or under control conditions. Seizure frequency in untreated animals or animals treated with MRgFUS without QA exhibited expected seizure rate fluctuations frequencies between the monitoring periods. In contrast, animals treated with PING targeting the intermediate-temporal aspect of the hippocampus exhibited substantial reductions in seizure frequency, with convulsive seizures being eliminated entirely in two animals. These findings suggest that PING could provide a useful alternative to invasive surgical interventions for treating drug resistant epilepsy, and perhaps for treating other neurological disorders in which aberrant neural circuitries play a role.Graphical abstractDownload : Download high-res image (302KB)Download : Download full-size image

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