Anticonvulsive effects of carbenoxolone on penicillin-induced epileptiform activity: An in vivo study

Bostanci, M. Ömer; Bağirici, Faruk

doi:10.1016/j.neuropharm.2006.08.008

Cited by 43 publications

(25 citation statements)

References 42 publications

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“…Gap junctions are penetrable for several ions and small molecules, contributing to the distribution of metabolites and signaling agents. Distributions of nutrients is suggested to be pro-convulsive, as it provides supply for the maintenance of seizures (Gigout et al, 2006; Bostanci and Bağirici, 2007). In contrast, buffering of K + and Glu is considered to be anticonvulsive (Wallraff et al, 2006) by reducing excess excitability.…”

Section: Discussionmentioning

confidence: 99%

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Recurrent seizure-like events are associated with coupled astroglial synchronization

Kékesi

Ioja

Szabó

et al. 2015

Front. Cell. Neurosci.

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Increasing evidence suggest that astrocytes significantly modulate neuronal function at the level of the tripartite synapse both in physiological and pathophysiological conditions. The global control of the astrocytic syncytium over neuronal networks, however, is still less recognized. Here we examined astrocytic signaling during epileptiform activity which is generally attributed to large-scale neuronal synchronization. We show that seizure-like events in the low-[Mg2+] in vitro epilepsy model initiate massive, long-range astrocytic synchronization which is spatiotemporally coupled to the synchronized neuronal activity reaching its maximum at the electrographic tonic/clonic transition. Cross-correlation analysis of neuronal and astrocytic Ca2+ signaling demonstrates that high degree of synchronization arises not only among astrocytes, but also between neuronal and astrocyte populations, manifesting in astrocytic seizure-like events. We further show that astrocytic gap junction proteins contribute to astrocytic synchronization since their inhibition by carbenoxolone (CBX) or Cx43 antibody increased the interictal interval and in 41% of slices completely prevented recurrent seizure-like activity. In addition, CBX also induced unsynchronized Ca2+ transients associated with decreasing incidence of epileptiform discharges afterwards. We propose therefore that local, unsynchronized astrocytic Ca2+ transients inhibit, while long-range, synchronized Ca2+ signaling contributes to the propagation of recurrent seizure-like events.

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Section: Discussionmentioning

confidence: 99%

“…The astrocytic synchronization mediated by gap junctions contributes to the propagation of seizures, providing an explanation why CBX treatment can be beneficial for in vivo epilepsy conditions (Bostanci and Bağirici, 2007). …”

Section: Discussionmentioning

confidence: 99%

Recurrent seizure-like events are associated with coupled astroglial synchronization

Kékesi

Ioja

Szabó

et al. 2015

Front. Cell. Neurosci.

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“…Such experiments have been performed in a variety of in vivo and in vitro models of epilepsy (Perez-Velazquez et al 1994; Ross et al 2000; Kohling et al 2001; Jahromi et al 2002; Szente et al 2002; Gajda et al 2003; Samoilova et al 2003, 2008; Bostanci and Bagirici 2006, 2007; Medina-Ceja et al 2008; Voss et al 2009). Most of these studies reported anticonvulsive effects of gap-junction blockade although opposite effects were observed by Voss et al (2009).…”

Section: A Role For Altered Gap-junction Coupling In Epilepsy?mentioning

confidence: 99%

Role of Astrocytes in Epilepsy

Coulter

Steinhäuser

2015

Cold Spring Harbor Perspectives in Medicine

196

150

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Astrocytes express ion channels, transmitter receptors, and transporters and, thus, are endowed with the machinery to sense and respond to neuronal activity. Recent studies have implicated that astrocytes play important roles in physiology, but these cells also emerge as crucial actors in epilepsy. Astrocytes are abundantly coupled through gap junctions allowing them to redistribute elevated K+ and transmitter concentrations from sites of enhanced neuronal activity. Investigation of specimens from patients with pharmacoresistant temporal lobe epilepsy and epilepsy models revealed alterations in expression, localization, and function of astroglial K+ and water channels. In addition, malfunction of glutamate transporters and the astrocytic glutamate-converting enzyme, glutamine synthetase, has been observed in epileptic tissue. These findings suggest that dysfunctional astrocytes are crucial players in epilepsy and should be considered as promising targets for new therapeutic strategies.

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“…1) is a hemisuccinate of glycyrrhetinic acid, which is a major active constituent of licorice (Glycyrrhiza glabra) root. It is used in the treatment of gastric ulcers in humans [1, 2] and has been attributed numerous pharmacological activities like anti-viral, anti-tumor, hepatoprotective and anti-inflammatory effects in experimental animals [3,4,5,6]. Recently, CBX has been demonstrated to block gap junction in animal models and expected to be an anti-epileptic agent for humans [7].…”

Section: Introductionmentioning

confidence: 99%

Inhaled Carbenoxolone Prevents Allergic Airway Inflammation and Airway Hyperreactivity in a Mouse Model of Asthma

Ram

Singh

et al. 2008

Int Arch Allergy Immunol

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Background: Asthma is a chronic respiratory disease, which needs a safer medication preferably in inhalation form. In view of this, we have evaluated the effect of inhaled carbenoxolone (CBX), a herbal-derived compound, on asthma in a mouse model. Methods: Mice were sensitized and challenged with ovalbumin (OVA) to develop certain characteristic features of asthma such as airway hyperreactivity (AHR), airway eosinophilia, lung inflammation and mucus hypersecretion. To evaluate the effect of CBX on the above asthmatic features, CBX (2.5, 5 and 10 mg/ml, 3 ml) or vehicle (water) was given by inhalation. AHR was determined using whole-body plethysmography. Infiltration of eosinophils was estimated by microscopy. Lung inflammation and mucus hypersecretion were assessed using hematoxylin and eosin, and periodic acid-Schiff staining, respectively. Th-2 cytokines, IL-4 and IL-5 were measured in bronchoalveolar lavage (BAL) fluid and IgE in sera. To identify the possible mode of CBX action, we measured corticosterone levels in the BAL fluid and 5-lipoxygenase (5-LO) expression in the lungs. Results: CBX (5 mg/ml) inhalation markedly alleviated AHR (p = 0.0032) and reduced lung inflammation and mucus hypersecretion. Also, it prevented the increase in IL-4 (p = 0.0192), IL-5 (p = 0.0116) and eosinophils (p < 0.0005) in the BAL fluid, and OVA-specific IgE levels (p = 0.00061) in sera. 5-LO expression was also markedly reduced. However, corticosterone levels were not affected. Conclusions: Inhaled CBX alleviates the asthmatic features in mice and could be a potent nebulized therapy in clinical asthma.

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Anticonvulsive effects of carbenoxolone on penicillin-induced epileptiform activity: An in vivo study

Cited by 43 publications

References 42 publications

Recurrent seizure-like events are associated with coupled astroglial synchronization

Recurrent seizure-like events are associated with coupled astroglial synchronization

Role of Astrocytes in Epilepsy

Inhaled Carbenoxolone Prevents Allergic Airway Inflammation and Airway Hyperreactivity in a Mouse Model of Asthma

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