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Causes of CNS Inflammation and Potential Targets for Anticonvulsants

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Abstract

Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood–brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

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Acknowledgments

The authors thank Iain Patefield and Melanie Gatt who provided medical writing assistance, and Andrea Bothwell who provided post-submission amendments, all of inScience Communications, Springer Healthcare. This assistance was funded by UCB Pharma. Mercé Falip has received funding for lectures from the Medical Department of UCB; Xavier Salas-Puig declares no conflict of interest. Carlos Cara is an employee of UCB Pharma.

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  1. Department of Neurology, Epilepsy Unit, Hospital de Bellvitge, Feixa Llarga S/N, 08907 Hospitalet de Llobregat, Barcelona, Spain

    Mercé Falip

  2. Epilepsy Unit, Hospital Vall D’Hebrón, Barcelona, Spain

    Xavier Salas-Puig

  3. UCB Pharma, Madrid, Spain

    Carlos Cara

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  1. Mercé Falip
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  2. Xavier Salas-Puig
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  3. Carlos Cara
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Correspondence to Mercé Falip.

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Falip, M., Salas-Puig, X. & Cara, C. Causes of CNS Inflammation and Potential Targets for Anticonvulsants. CNS Drugs 27, 611–623 (2013). https://doi.org/10.1007/s40263-013-0078-6

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