CHANGES IN GLUTAMATE LEVELS IN AN EPILEPTIC FOCUS
Abstract number :
1.106
Submission category :
Year :
2003
Submission ID :
2079
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Seyed M. Mirsattari, John R. Ives, L. Stan Leung, Robert Bartha Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada; Imaging Research Laboratories, Robarts Research Institute, London, ON, Canada
Increased metabolic demands associated with excessive neuronal firing within an epileptic focus can alter energy supply and result in decreased energy-utilizing process such as protein synthesis. Glutamate plays a critical role in protein biosynthesis. However, the metabolic changes associated with interictal spikes are not well understood. The purpose of this study is to characterize changes in total glutamate levels, which play a critical role in protein biosynthesis, in an epileptic focus as a function of time.
Two adult male Spargue-Dawley rats (1 control) were anesthetized with 1.5-2% isoflurane and mechanically ventilated. Fentanyl 0.1 mg/kg followed by 0.01 mg/kg/h and vecuronium 1.5 mg/kg followed by 7.5 mg/kg/h were injected into the tail vein. The animals were placed in a MRI compatible stereotactic frame. One burr hole ([lt]0.8 mm2) was made over each primary visual cortex. One animal was injected with 0.2 [micro]l of 100 IU sodium penicillin G at 0.8 mm below the cortical surface in the right primary visual cortex. EEG (Ives US Patent No: 5,445,162 ) was used to determine the presence and quantity of epileptic spikes after penicillin injection. Baseline glutamate level was obtained from the control animal. Two carbon fiber EEG electrodes were placed above the dura and silver/silver chloride electrodes were used for reference, ground, and electrocardiogram (ECG) monitoring. Other physiologic states including ECG, heart rates, oxygen saturation, end-tidal CO2, and temperature were monitored simultaneously. LASER localized short TE 1H MRS (TE/TR= 40/3200 msec) was obtained on a 4.0 T Siemens/Varain whole body human research MRI with custom designed surface RF coil. Macromolecule subtraction, lineshape correction, and metabolite template modeling were used to quantify the glutamate levels from a single voxel centered in the right primary visual cortx (80 [micro]L) following injection of penicillin. The water concentration in the same brain tissue was used as a reference to determine absolute glutamate concentrations. The animals were sacrificed and perfused with formalin to verify the injection sites.
There was a reduction in the total glutamate level compared to control during the first two hours following the initiation of epileptiform discharges.
These preliminary data show reduced glutamate level in the active epileptic focus of an experimental model of occipital epilepsy.
[Supported by: Canadian Institutes of Health Research and Robarts Research Institute]