MECHANISMS OF SEIZURE REDUCTION BY LOW FREQUENCY ELECTRICAL STIMULATION
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Case Western Reserve University School of Graduate Studies / OhioLINK
2014
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=case1399474125 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-case13994741252021-08-03T06:24:36Z MECHANISMS OF SEIZURE REDUCTION BY LOW FREQUENCY ELECTRICAL STIMULATION Toprani, Sheela C. Biomedical Engineering Biomedical Research Biophysics Neurology Neurosciences epilepsy mesial temporal lobe epilepsy seizure reduction deep brain stimulation low frequency stimulation GABA GABAB afterhyperpolarization slow afterhyperpolarization Mesial temporal lobe epilepsy (MTLE) is the most common and medically refractory form of epilepsy. As an alternative to surgical resection, MTLE has been treated with vagal nerve stimulation and deep brain electrical stimulation (DBS) of gray matter with limited success. Stimulation of a white matter tract connecting the hippocampi could maximize treatment efficacy and extent. We tested low-frequency electrical stimulation (LFS) of a novel target that enables simultaneous targeting of bilateral hippocampi: the ventral hippocampal commissure (VHC) with a novel in-vitro slice preparation containing bilateral hippocampi connected by the VHC. The goals of this study are: (i) To understand the role of hippocampal interplay in seizure propagation and reduction by commissural fiber tract stimulation, (ii) To develop and test a novel DBS paradigm for hippocampal seizure reduction, and (iii) To test the role of long-lasting hyperpolarization in mediating the anti-epileptic effects of LFS. The third objective is divided into two parts as follows: (a) Pharmacologically assess whether GABAB receptors are necessary for seizure reduction by LFS and (b) Pharmacologically assess whether the sAHP is necessary for seizure reduction by LFS. To achieve these aims, LFS is applied to the VHC as electrophysiological techniques are combined with signal processing to estimate several metrics of epilepsy. Bilateral epileptiform activity in this preparation is highly correlated between hippocampi. Application of LFS to the VHC reduces seizures in bilateral hiipocampi during and after stimulation in an amplitude and frequency dependent manner. Importantly, enhanced post-stimulation 1-Hz spiking correlates with long-lasting seizure reduction and both are heightened by targeting bilateral hippocampi via the VHC. Understanding the mechanisms of seizure reduction by LFS is important for minimizing side effects of this potential therapy and maximizing efficacy. This study shows depolarization blocking, LTD/LTP and GABAA are not involved in seizure reduction by LFS. Rather, decreased neuronal excitability by LFS-induction of long-lasting hyperpolarization (LLH) composed of (1) the GABAB slow inhibitory post-synaptic potential (IPSP) and (2) the slow afterhyperpolarization (sAHP) were found to be necessary for seizure reduction by LFS. These insights into the mechanisms of DBS, specifically LFS, promote safer implementation and optimization of this promising therapy. 2014-06-12 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1399474125 http://rave.ohiolink.edu/etdc/view?acc_num=case1399474125 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biomedical Engineering Biomedical Research Biophysics Neurology Neurosciences epilepsy mesial temporal lobe epilepsy seizure reduction deep brain stimulation low frequency stimulation GABA GABAB afterhyperpolarization slow afterhyperpolarization |
| spellingShingle |
Biomedical Engineering Biomedical Research Biophysics Neurology Neurosciences epilepsy mesial temporal lobe epilepsy seizure reduction deep brain stimulation low frequency stimulation GABA GABAB afterhyperpolarization slow afterhyperpolarization Toprani, Sheela C. MECHANISMS OF SEIZURE REDUCTION BY LOW FREQUENCY ELECTRICAL STIMULATION |
| author |
Toprani, Sheela C. |
| author_facet |
Toprani, Sheela C. |
| author_sort |
Toprani, Sheela C. |
| title |
MECHANISMS OF SEIZURE REDUCTION BY LOW FREQUENCY ELECTRICAL STIMULATION |
| title_short |
MECHANISMS OF SEIZURE REDUCTION BY LOW FREQUENCY ELECTRICAL STIMULATION |
| title_full |
MECHANISMS OF SEIZURE REDUCTION BY LOW FREQUENCY ELECTRICAL STIMULATION |
| title_fullStr |
MECHANISMS OF SEIZURE REDUCTION BY LOW FREQUENCY ELECTRICAL STIMULATION |
| title_full_unstemmed |
MECHANISMS OF SEIZURE REDUCTION BY LOW FREQUENCY ELECTRICAL STIMULATION |
| title_sort |
mechanisms of seizure reduction by low frequency electrical stimulation |
| publisher |
Case Western Reserve University School of Graduate Studies / OhioLINK |
| publishDate |
2014 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=case1399474125 |
| work_keys_str_mv |
AT topranisheelac mechanismsofseizurereductionbylowfrequencyelectricalstimulation |
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1719436278084141056 |