Glia and epilepsy: excitability and inflammation

Devinsky, Orrin; Vezzani, Annamaria; Najjar, Souhel; Lanerolle, Nihal C. de; Rogawski, Michael A.

doi:10.1016/j.tins.2012.11.008

Cited by 693 publications

(614 citation statements)

References 116 publications

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“…Δ9-THC also transiently activates and desensitizes the transient receptor potential (TRP) channels TRPA1, TRPV1, and TRPV2 [97][98][99]. Given the synergistic relation between seizures and inflammation [100][101][102], the cannabinoid system provides a novel strategy to target both segments of this feedback cycle.…”

Section: δ9-thcmentioning

confidence: 99%

Cannabinoids and Epilepsy

et al. 2015

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Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabisbased antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro-and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.

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Section: δ9-thcmentioning

confidence: 99%

Cannabinoids and Epilepsy

et al. 2015

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“…For example, cannabinoids have been shown to influence epileptic activity, although results reporting the proconvulsive or anti-epileptic effects of CB1R ligands are controversial [60,61]. On the other hand, astrocytes have been shown to contribute to epileptiform activity [62][63][64][65][66].…”

Section: Impact Of Astrocytes On the Behavioural Effects Of Endocannamentioning

confidence: 99%

Astrocytes in endocannabinoid signalling

Navarrete

Díez

Araque

2014

Phil. Trans. R. Soc. B

112

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Astrocytes are emerging as integral functional components of synapses, responding to synaptically released neurotransmitters and regulating synaptic transmission and plasticity. Thus, they functionally interact with neurons establishing tripartite synapses: a functional concept that refers to the existence of communication between astrocytes and neurons and its crucial role in synaptic function. Here, we discuss recent evidence showing that astrocytes are involved in the endocannabinoid (ECB) system, responding to exogenous cannabinoids as well as ECBs through activation of type 1 cannabinoid receptors, which increase intracellular calcium and stimulate the release of glutamate that modulates synaptic transmission and plasticity. We also discuss the consequences of ECB signalling in tripartite synapses on the astrocyte-mediated regulation of synaptic function, which reveal novel properties of synaptic regulation by ECBs, such as the spatially controlled dual effect on synaptic strength and the lateral potentiation of synaptic efficacy. Finally, we discuss the potential implications of ECB signalling for astrocytes in brain pathology and animal behaviour.

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“…[28,29]). Furthermore, in inflammatory conditions TNF-a may play a role in causing hyperalgesia or neuropathic pain [30][31][32] and cytokines are also upregulated in epilepsy [33,34]. As the enhanced excitability in inflammation could be evoked by an upregulation of Na þ current density [35,36], here we also asked whether the release of cytokines from microglia could influence the Na þ current density in cultured hippocampal neurons.…”

Section: Introductionmentioning

confidence: 99%

“…To answer this question, we investigated whether the addition of microglia and their activation with lipopolysaccharides (LPS) (e.g. [28,34]) influences the Na þ current density and whether a cytokine supplementation to the cell cultures elicits an effect comparable with the addition of activated microglia.…”

Section: Introductionmentioning

confidence: 99%

Regulation of neuronal excitability by release of proteins from glial cells

Igelhorst

Niederkinkhaus

Karus

et al. 2015

Phil. Trans. R. Soc. B

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Effects of glial cells on electrical isolation and shaping of synaptic transmission between neurons have been extensively studied. Here we present evidence that the release of proteins from astrocytes as well as microglia may regulate voltage-activated Na þ currents in neurons, thereby increasing excitability and speed of transmission in neurons kept at distance from each other by specialized glial cells. As a first example, we show that basic fibroblast growth factor and neurotrophin-3, which are released from astrocytes by exposure to thyroid hormone, influence each other to enhance Na þ current density in cultured hippocampal neurons. As a second example, we show that the presence of microglia in hippocampal cultures can upregulate Na þ current density. The effect can be boosted by lipopolysaccharides, bacterial membrane-derived stimulators of microglial activation. Comparable effects are induced by the exposure of neuron-enriched hippocampal cultures to tumour necrosis factor-a, which is released from stimulated microglia. Taken together, our findings suggest that release of proteins from various types of glial cells can alter neuronal excitability over a time course of several days. This explains changes in neuronal excitability occurring in states of thyroid hormone imbalance and possibly also in seizures triggered by infectious diseases.

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Glia and epilepsy: excitability and inflammation

Cited by 693 publications

References 116 publications

Cannabinoids and Epilepsy

Cannabinoids and Epilepsy

Astrocytes in endocannabinoid signalling

Regulation of neuronal excitability by release of proteins from glial cells

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