Neuron–glia interactions in the pathophysiology of epilepsy


Epilepsy is a neurological disorder afflicting ~65 million people worldwide. It is caused by aberrant synchronized firing of populations of neurons primarily due to imbalance between excitatory and inhibitory neurotransmission. Hence, the historical focus of epilepsy research has been neurocentric. However, the past two decades have enjoyed an explosion of research into the role of glia in supporting and modulating neuronal activity, providing compelling evidence of glial involvement in the pathophysiology of epilepsy. The mechanisms by which glia, particularly astrocytes and microglia, may contribute to epilepsy and consequently could be harnessed therapeutically are discussed in this Review.

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Fig. 1: Interplay between CNS insult, reactive gliosis and seizures.
Fig. 2: Regulation of synaptic transmitter homeostasis and energy metabolites by astrocytes.
Fig. 3: Disintegration of perineuronal nets in glioma-associated epilepsy.
Fig. 4: Changes in the extracellular matrix as contributors to epilepsy.


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This work was supported by grants from the US National Institutes of Health (RO1-NS036692, RO1-NS082851 and RO1-NS052634).

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Nature Reviews Neuroscience thanks D. Coulter and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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H.S., D.C.P. and B.P.T. researched data for the article and made a substantial contribution to the discussion of content and the writing, review and editing of the manuscript before submission. L.C. researched data for the article.

Correspondence to Harald Sontheimer.

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An anticonvulsant that acts by activating inhibitory postsynaptic neuronal GABA type A (GABAA) receptors. Phenobarbital can activate GABAA receptors independent of GABA, but it also potentiates the effects of GABA.


Any condition or disease that occurs spontaneously or with an unknown aetiology.

Gliotic scar

A dense fibrous mass of reactive glia formed in response to CNS injury. It is a part of the tissue-remodelling process that occurs following injury and provides both beneficial and detrimental effects in a context-dependent manner.


A pathological stiffening of tissue at the injury site due to overgrowth of fibrous connective tissue that replaces original tissue.


A convulsant that acts by directly antagonizing GABA type A receptor-mediated inhibitory neurotransmission and therefore is often used experimentally to induce seizures in animals.

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