Effects of high frequency electrical stimulation and R-verapamil on seizure susceptibility and glutamate and GABA release in a model of phenytoin-resistant seizures

Luna-Munguía, Hiram; Orozco‐Suárez, Sandra; Rocha, Luisa

doi:10.1016/j.neuropharm.2011.05.027

Cited by 45 publications

(26 citation statements)

References 78 publications

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“…However, an important condition to be considered is that a low ambient GABA represents an inadequate situation to activate GABA A receptors mediating tonic inhibition with a consequent facilitation of seizure activity, depression-like, and anxiety-like behaviors (Merali et al, 2004 ; Maguire and Mody, 2008 ; Hines et al, 2012 ). Our experiments revealed reduced GABA tissue levels in the neocortex of patients with TLE and comorbid anxiety and depression, a situation that can be associated with the low GABA release in pharmacoresistant epilepsy described by other authors (During and Spencer, 1993 ; Luna-Munguia et al, 2011 ).…”

Section: Discussionsupporting

confidence: 77%

GABAergic Alterations in Neocortex of Patients with Pharmacoresistant Temporal Lobe Epilepsy Can Explain the Comorbidity of Anxiety and Depression: The Potential Impact of Clinical Factors

Rocha

Alonso-Vanegas

Martínez‐Juárez

et al. 2015

Front. Cell. Neurosci.

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Temporal lobe epilepsy (TLE) is a chronic neurodegenerative disease with a high prevalence of psychiatric disorders. Temporal neocortex contributes to either seizure propagation or generation in TLE, a situation that has been associated with alterations of the γ-amino-butyric acid (GABA) system. On the other hand, an impaired neurotransmission mediated by GABA in temporal neocortex has also been involved with the pathophysiology of psychiatric disorders. In spite of these situations, the role of the necortical GABA system in the comorbidity of TLE and mood disorders has not been investigated. The present study was designed to identify alterations in the GABA system such as binding to GABAA and GABAB receptors and benzodiazepine site, the tissue content of GABA and the expression of the mRNA encoding the α1–6, β1–3, and γ GABAA subunits, in the temporal neocortex of surgically treated patients with TLE with and without anxiety, and/or depression. Neocortex of patients with TLE and comorbid anxiety and/or depression showed increased expression of the mRNA encoding the γ2-subunit, reduced GABAB-induced G-protein activation in spite of elevated GABAB binding, and lower tissue content of GABA when compared to autopsy controls. Some of these changes significantly correlated with seizure frequency and duration of epilepsy. The results obtained suggest a dysfunction of the GABAergic neurotransmission in temporal neocortex of patients with TLE and comorbid anxiety and/or depression that could be also influenced by clinical factors such as seizure frequency and duration of illness.

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Section: Discussionsupporting

confidence: 77%

GABAergic Alterations in Neocortex of Patients with Pharmacoresistant Temporal Lobe Epilepsy Can Explain the Comorbidity of Anxiety and Depression: The Potential Impact of Clinical Factors

Rocha

Alonso-Vanegas

Martínez‐Juárez

et al. 2015

Front. Cell. Neurosci.

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“…However, a different optogenetic strategy for seizure suppression that mimics electrical HFS protocols by activating neurons can also effective. Electrical HFS has been thought to suppress seizures by generating a depolarization block related to the inactivation of sodium channels (10, 11) or driving GABA release during stimulation (24, 25). In the present study, histological analyses show that mostly interneurons express ChR2 in the Thy1-ChR2 mice and thus GABA release could be enhanced by optical stimulation together with the activation of some pyramidal cells.…”

Section: Discussionmentioning

confidence: 99%

Seizure Suppression by High Frequency Optogenetic Stimulation Using In Vitro and In Vivo Animal Models of Epilepsy

Chiang¹,

Ladas²,

Gonzalez‐Reyes

et al. 2014

Brain Stimulation

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Background: Electrical high frequency stimulation (HFS) has been shown to suppress seizures. However, the mechanisms of seizure suppression remain unclear and techniques for blocking specific neuronal populations are required. Objective: The goal is to study the optical HFS protocol on seizures as well as the underlying mechanisms relevant to the HFS-mediated seizure suppression by using optogenetic methodology. Methods: Thy1-ChR2 transgenic mice were used in both vivo and in vitro experiments. Optical stimulation with pulse trains at 20 and 50 Hz was applied on the focus to determine its effects on in vivo seizure activity induced by 4-AP and recorded in the bilateral and ipsilateral-temporal hippocampal CA3 regions. In vitro methodology was then used to study the mechanisms of the in vivo suppression. Results: Optical HFS was able to generate 82.4 % seizure suppression at 50 Hz with light power of 6.1 mW and 80.2 % seizure suppression at 20 Hz with light power of 2.0 mW. The suppression percentage increased by increasing the light power and saturated when the power reached above-mentioned values. In vitro experimental results indicate that seizure suppression was mediated by activation of GABA receptors. Seizure suppression effect decreased with continued application but the suppression effect could be restored by intermittent stimulation. Conclusions: This study shows that optical stimulation at high frequency targeting an excitatory opsin has potential therapeutic application for fast control of an epileptic focus. Furthermore, electrophysiological observations of extracellular and intracellular signals reveled that GABAergic neurotransmission activated by optical stimulation was responsible for the suppression.

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“…These findings might be of clinical relevance for central nervous system diseases characterized by excessive glutamate release such as epilepsy (Thomas et al, 2003(Thomas et al, , 2004(Thomas et al, , 2005Potschka, 2010). Considering that glutamate is highly concentrated in the extracellular space during the ictal period (During and Spencer, 1993;Wilson et al, 1996;Cavus et al, 2005;Luna-Munguia et al, 2011), this might imply that signaling of glutamate via the endothelial NMDA receptor is a possible mechanism of MRP2 upregulation in the epileptic brain. Studies in both rodent epilepsy models and in human epileptic tissue previously revealed an overexpression of this blood-brain barrier efflux transporter (Aronica et al, 2004(Aronica et al, , 2012van Vliet et al, 2005;Hoffmann and Löscher, 2007).…”

Section: Glutamate Upregulates Mrp2mentioning

confidence: 91%

Glutamate-Mediated Upregulation of the Multidrug Resistance Protein 2 in Porcine and Human Brain Capillaries

Luna-Munguía

Salvamoser

Pascher

et al. 2014

J Pharmacol Exp Ther

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As a member of the multidrug-resistance associated protein (MRP) family, MRP2 affects the brain entry of different endogenous and exogenous compounds. Considering the role of this transporter at the blood-brain barrier, the regulation is of particular interest. However, there is limited knowledge regarding the factors that regulate MRP2 in neurologic disease states. Thus, we addressed the hypothesis that MRP2 might be affected by a glutamateinduced signaling pathway that we previously identified as one key mechanism in the regulation of P-glycoprotein.

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Effects of high frequency electrical stimulation and R-verapamil on seizure susceptibility and glutamate and GABA release in a model of phenytoin-resistant seizures

Cited by 45 publications

References 78 publications

GABAergic Alterations in Neocortex of Patients with Pharmacoresistant Temporal Lobe Epilepsy Can Explain the Comorbidity of Anxiety and Depression: The Potential Impact of Clinical Factors

GABAergic Alterations in Neocortex of Patients with Pharmacoresistant Temporal Lobe Epilepsy Can Explain the Comorbidity of Anxiety and Depression: The Potential Impact of Clinical Factors

Seizure Suppression by High Frequency Optogenetic Stimulation Using In Vitro and In Vivo Animal Models of Epilepsy

Glutamate-Mediated Upregulation of the Multidrug Resistance Protein 2 in Porcine and Human Brain Capillaries

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