Abstracts

Rationale: The current study was the first step in evaluating different brain stimulation waveforms for the treatment of epilepsy. A rat model of epilepsy with surgically implanted electrodes was used. Development of stimulation and data-acquisition equipment was necessary for this study. The project required a rat brain stimulation device, electrodes for monitoring electroencephalography (EEG), and an objective, reliable technique for measuring behavioral seizures. Methods: This protocol was approved by the IACUC at George Mason University and all surgeries were performed under sterile conditions. 250-300 g Sprague-Dawley rats were used. Under general anesthesia, electrodes were placed into the cortex, and the electrode socket was cemented to the skull with sterile dental cement. The electrode socket had eight electrode plugs and an open hole for Kainate injection. A subcutaneous cranial electrode was placed for the referential stimulation and two for recording EEG. An accelerometer was cemented to the electrode plug. On post-operative day seven, Kainate was injected through the open plug hole into the cortex and the rat was placed in a small clear plastic enclosure that would allow free movement while assessing behavioral responses. The rat was attached to the recording/stimulating instrument for recording EEG and accelerometry. Each rat was observed for one hour for seizure activity while EEG and accelerometry data was recorded. Results: Three different types of behavioral seizures were observed including head nodding, whole body shaking, and forelimb clonus.  These seizure activities were reliably captured by accelerometry and the different types of seizures could be differentiated by accelerometry.  The EEG data did not directly correspond to the observed seizure behavior or the accelerometry data.  There was evidence of seizure activity on EEG that was not recorded by accelerometry or observable seizure activity. Conclusions: Accelerometry in this rat model of epilepsy has the ability to reliably measure behavioral seizure activity and may be able to objectively differentiate seizure types.  Compared to EEG, accelerometry provides more limited measures of seizure activity but measures that reflect correlates of clinical rather that the electrographic seizures.  The combination of these two measures together provides comprehensive characterization of the seizure activity that can be used to assess the effectiveness of stimulation interventions. Funding: Internal grant from Inova and George Mason University