Background: Deep brain stimulation (DBS) has emerged as a potential therapeutic strategy in the treatment of neurological disorders including epilepsy. However, the cellular mechanism responsible for the effects of DBS remains largely undefined. Therefore, using electrophysiological approach, we aimed to determine the antiepileptic effects and restorative potential of low frequency stimulation (LFS) on amygdala kindling-induced changes in electrophysiological properties of rat hippocampal CA1 pyramidal neurons.
Methods: Animals were kindled by electrical stimulation of amygdala in a rapid kindling manner (12 times per day). In one group of animals, immediately after termination of daily 12 rapid kindling stimulations, the kindling site was subjected to 4 packages of LFS at intervals of 5 min (each package contained 200 monophasic square-wave pulses, 0.1 ms pulse duration at 1 Hz). Whole cell patch clamp recording under current clamp conditions was performed on visually identified pyramidal neurons in hippocampal slice preparations obtained from amygdala-kindled rats and the rats receiving LFS.
Results: Kindling of the right basolateral amygdala profoundly affected spontaneous firing behavior and repetitive discharge characteristics of pyramidal neuronal electrophysiological properties. Application of LFS at the kindling site almost completely prevented the development of epilepsy and the disruptive effects of kindling on neuronal electrical activity through restoration of the normal electrophysiological characteristics.
Conclusions: The results of this study implied that application of LFS during kindling acquisition prevents the kindling induced changes in functional electrical properties of CA1 pyramidal neurons, suggesting that this action may be involved in the antiepileptogenic mechanism of LFS.
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http://dx.doi.org/10.1016/j.brs.2012.11.001 | DOI Listing |
JMIR Med Inform
December 2024
University Emergency Department, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
J Exp Pharmacol
September 2024
Department of Pharmaceutical Science, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
Background: Human monoacylglycerol lipase (MGL) is accountable for the hydrolysis of 2-arachidonoylglycerol (2-AG), thus contributing pivotally to neuroprotection because 2-AG is the main source of arachidonic acid, the precursor of prostaglandins production. Inhibiting MGL reduces inflammatory damage in the ischemic brain and enhances cerebral blood flow. Plants have been reported for their neuroprotective effect, such as on pentylenetetrazol (PTZ)-induced kindling seizures in mice, by reducing the seizures and restoring behavioral and biochemical changes, although the mechanism is not described.
View Article and Find Full Text PDFEpilepsia
October 2024
Departments of Pharmacology and Pharmaceutical Analysis, School of Pharmacy, Qingdao University Medical College, Qingdao, China.
Objective: Pharmacological activation of neuronal Kv7 channels by the antiepileptic drug retigabine (RTG; ezogabine) has been proven effective in treating partial epilepsy. However, RTG was withdrawn from the market due to the toxicity caused by its phenazinium dimer metabolites, leading to peripheral skin discoloration and retinal abnormalities. To address the undesirable metabolic properties of RTG and prevent the formation of phenazinium dimers, we made chemical modifications to RTG, resulting in a new RTG derivative, 1025c, N,N'-{4-[(4-fluorobenzyl) (prop-2-yn-1-yl)amino]-1,2-phenylene}bis(3,3-dimethylbutanamide).
View Article and Find Full Text PDFBioorg Chem
October 2024
Department of Chemistry, Faculty of Arts and Sciences, Gaziantep University, 27310 Gaziantep, Turkey.
Antiepileptic drugs (AEDs) are used in the treatment of epilepsy, a neurodegenerative disease characterized by recurrent and untriggered seizures that aim to prevent seizures as a symptomatic treatment. However, they still have significant side effects as well as drug resistance. In recent years, especially 1,3,4-thiadiazoles and 1,2,4-triazoles have attracted attention in preclinical and clinical studies as important drug candidates owing to their anticonvulsant properties.
View Article and Find Full Text PDFImmunity
May 2024
Ben May Department of Cancer Research, The University of Chicago, Chicago, IL 60615, USA. Electronic address:
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