DENTATE GYRUS HYPEREXCITABILITY AS A CONSEQUENCE OF STATUS EPILEPTICUS: EVOLUTION AND MODULATION BY NEUROPROTECTIN D1
Document Type
Presentation
Start Date
22-10-2010 3:00 PM
End Date
22-10-2010 4:30 PM
Description
Epilepsy is a neurological disorder that occurs when delicate excitatory-inhibitory oscillations become unbalanced within the brain, and the threshold for seizure activity is decreased. Diets enriched in omega-3 fatty acids, such as Docosahexaenoic acid (DHA), are effective in protecting vulnerable inhibitory networks in animal models of epilepsy. We hypothesize that Neuroprotectin D1 (NPD1), a lipid derivative of DHA, is the key mediator responsible for the interneuron survival within the dentate gyrus (DG) during the development of epilepsy. In this project, we assessed DG hyperexcitability in vivo as a consequence of status epilepticus (SE) and determined if NPD1 modulated DG hyperexcitability. lntracerebroventricular cannulas and bipolar electrodes were implanted into the third ventricle and the DG, respectively, in adult male Wistar rats. Seven days after surgery, the pilocarpine model was used to induce SE and provoke the onset of epileptogenesis. Control animals received only saline. Following 14 days of monitoring, hyperexcitability assessment was performed by stimulating the DG with 6 consecutive subconvulsive electrical stimulations (50uAmp). Evoked behavioral responses were graded according to the Racine Scale. EEG recordings from the DG were analyzed for electrical afterdischarges (AD), and the variables examined included: duration and spike quantification. Preliminary results revealed that sub-convulsive stimulation evokes abnormal epileptic behaviors in 50% of animals post-SE. AD duration was prolonged in animals with evoked epileptic activity (average AD duration: na'fve behavior -14.27 sec, epileptic behavior -31.48 sec). Finally, NPD1 treated animals exhibiting epileptic behavior had smaller AD duration as compared to CSF/vehicle treated animals (NPD1 -5.69 seconds, CSF -57.27 sec). These preliminary results suggest epileptogenic markers, such as hyperexcitability, can be detected with our assessment tool. Furthermore, the impact of NPD1 's protection of interneurons will be understood more completely as we determine if excitatory-inhibitory mechanisms are preserved during epileptogenesis.
Recommended Citation
Quebedeaux, Tabitha; Sfondouris, J. L.; Musto, A. E.; and Bazan, N. G., "DENTATE GYRUS HYPEREXCITABILITY AS A CONSEQUENCE OF STATUS EPILEPTICUS: EVOLUTION AND MODULATION BY NEUROPROTECTIN D1" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 17.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/poster2/17
DENTATE GYRUS HYPEREXCITABILITY AS A CONSEQUENCE OF STATUS EPILEPTICUS: EVOLUTION AND MODULATION BY NEUROPROTECTIN D1
Epilepsy is a neurological disorder that occurs when delicate excitatory-inhibitory oscillations become unbalanced within the brain, and the threshold for seizure activity is decreased. Diets enriched in omega-3 fatty acids, such as Docosahexaenoic acid (DHA), are effective in protecting vulnerable inhibitory networks in animal models of epilepsy. We hypothesize that Neuroprotectin D1 (NPD1), a lipid derivative of DHA, is the key mediator responsible for the interneuron survival within the dentate gyrus (DG) during the development of epilepsy. In this project, we assessed DG hyperexcitability in vivo as a consequence of status epilepticus (SE) and determined if NPD1 modulated DG hyperexcitability. lntracerebroventricular cannulas and bipolar electrodes were implanted into the third ventricle and the DG, respectively, in adult male Wistar rats. Seven days after surgery, the pilocarpine model was used to induce SE and provoke the onset of epileptogenesis. Control animals received only saline. Following 14 days of monitoring, hyperexcitability assessment was performed by stimulating the DG with 6 consecutive subconvulsive electrical stimulations (50uAmp). Evoked behavioral responses were graded according to the Racine Scale. EEG recordings from the DG were analyzed for electrical afterdischarges (AD), and the variables examined included: duration and spike quantification. Preliminary results revealed that sub-convulsive stimulation evokes abnormal epileptic behaviors in 50% of animals post-SE. AD duration was prolonged in animals with evoked epileptic activity (average AD duration: na'fve behavior -14.27 sec, epileptic behavior -31.48 sec). Finally, NPD1 treated animals exhibiting epileptic behavior had smaller AD duration as compared to CSF/vehicle treated animals (NPD1 -5.69 seconds, CSF -57.27 sec). These preliminary results suggest epileptogenic markers, such as hyperexcitability, can be detected with our assessment tool. Furthermore, the impact of NPD1 's protection of interneurons will be understood more completely as we determine if excitatory-inhibitory mechanisms are preserved during epileptogenesis.
Comments
See abstract book page 61